Index

A

Abscopal effect. See Bystander effects

Absolute risk.

See also Excess absolute risk

defined, 132, 373

Absorbed dose

atomic bomb survivors, 20, 27, 142

and biological effect, 20

defined, xi, 373

neutron weighting factor, 296-297

photon energy fluence and, 22

Achondroplasia, 92, 98, 125

Activity

defined, 373

units of, 373

Acute myocardial infarction, 95

ada gene, 36, 37

Adaptive response

animal studies, 51, 52, 53, 55, 78-79, 251

bacteria, 50

bystander effect and, 55

and cancer risk assessment, 250-251

cell cycle alterations, 51, 53

for cell lethality, 51, 52, 55, 78

in Chernobyl children, 51

to chromosomal aberrations, 51, 53, 55

cumulative effect of multiple low doses, 53

DDREF and, 78-79

to DNA damage and repair, 39, 50, 51, 52, 53, 251

dose fractionation and, 78

dose-response relationships, 45, 50-53, 62, 89

genotype and, 53

and hormesis, 333

in humans, 50

to iodine-131, 51

in lymphocytes, 51, 53

malignant transformation as, 51-52, 62, 78-79

in mammalian cells in vitro, 51, 52, 62

mechanisms, 11, 29, 39, 51-53

to medical uses of radiation, 51

in mice, 51, 52, 53, 55, 78

microarray expression studies, 39, 53

modeling, 250-251

mutagenesis as, 51

to occupational exposures, 51, 53

to oxidative stress, 50

priming dose and, 51-53, 55, 78, 251

radiation resistance as, 37, 51

research needs, 53

signal transduction pathways, 51, 53

in tumorigenesis, 12, 51-52, 78-79, 250-251

variation in, 51

Additive effects, 148, 150, 297, 373

Adenine phosphoribosyltransferase, 46

Adenocarcinomas, 50, 74, 76

Adenomas, 69, 151, 168

Adrenal cortical carcinoma, 86, 161

Adriamycin, 130

Adult Health Study, 142, 150, 151, 153

Aflatoxins, 242

Air and space travel, 3, 19

occupational exposures, 204

Alcohol consumption, 242

All-Union Distributed Registry, 202

Alpha particles

and bone cancer, 87, 269

bystander effect, 53-54, 55

cell killing/lethality, 54

chromosome aberrations, 53

genetic susceptibility, 53, 87

and genomic instability, 70, 71

internal contamination, 199-200

LET value, 21

and leukemia, 71

and liver cancer, 68

and lung cancer, 242

mutagenesis, 53, 54, 68

RBE, 71

and tumorigenesis, 70

Amelogenesis imperfecta, 98

American Registry of Radiologic Technologists, 205

Animal studies.

See also specific animals

adaptive response, 78-79, 251

bone cancer, 74

breast/mammary cancer, 74, 82, 83, 88

DDREF from, 77-79, 254-258

DNA damage and repair mechanisms, 34, 36, 42, 52, 69, 71

dose-response relationships, 73-75, 89, 245

extrapolation to humans, 73, 96-98, 109-111, 114, 115

genetic effects of radiation, 12, 68-70, 73, 82-83, 92, 96-97

genetic susceptibility to cancer, 68-70, 71, 73, 82-83, 87-88, 89

of growth and developmental effects, 115

of hormesis, 334

leukemia, 68-70, 71, 72, 73-74, 87

life-shortening effects of radiation, 246

limitations of, 245

lung cancer, 28, 50, 74, 76, 87

lymphoma, 68, 73, 74, 76, 78

mutation rates, 68-70, 96-98

neutron RBE, 28-29, 68, 126

predictive value, 73, 75, 241

radiosensitivity, 34, 69, 71, 82-83

skin cancer, 74, 75, 76, 87

tumorigenesis, radiation-induced, 11, 12, 67, 68-70, 73-79, 82-83, 89, 240, 241, 246

X-ray exposure, 68, 69, 100-101

Aniridia, 98

Ankylosing spondylitis cohorts

bone cancer, 164

breast cancer, 164-165, 176, 177

cancer mortality, 164, 165

cohort description, 164

colon cancer, 164

dosimetry, 164, 165

esophageal cancer, 164

kidney cancer, 164

leukemia, 164, 165, 183, 289

lung cancer, 164, 174

malignant lymphoma, 164

modeling cancer risk in, 287

multiple myeloma, 164

pancreatic cancer, 164

prostate cancer, 164, 288

radiotherapy-related cancer risks, 164-165, 174, 176, 177, 185, 287, 288, 289

stomach cancer, 164, 185, 287, 288, 289

urinary tract cancer, 164, 288



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Index A modeling, 250-251 DNA damage and repair mechanisms, 34, 36, mutagenesis as, 51 42, 52, 69, 71 Abscopal effect. See Bystander effects to occupational exposures, 51, 53 dose-response relationships, 73-75, 89, 245 Absolute risk. See also Excess absolute risk to oxidative stress, 50 extrapolation to humans, 73, 96-98, 109-111, defined, 132, 373 priming dose and, 51-53, 55, 78, 251 114, 115 Absorbed dose radiation resistance as, 37, 51 genetic effects of radiation, 12, 68-70, 73, atomic bomb survivors, 20, 27, 142 research needs, 53 82-83, 92, 96-97 and biological effect, 20 signal transduction pathways, 51, 53 genetic susceptibility to cancer, 68-70, 71, defined, xi, 373 in tumorigenesis, 12, 51-52, 78-79, 250-251 73, 82-83, 87-88, 89 neutron weighting factor, 296-297 variation in, 51 of growth and developmental effects, 115 photon energy fluence and, 22 Additive effects, 148, 150, 297, 373 of hormesis, 334 Achondroplasia, 92, 98, 125 Adenine phosphoribosyltransferase, 46 leukemia, 68-70, 71, 72, 73-74, 87 Activity Adenocarcinomas, 50, 74, 76 life-shortening effects of radiation, 246 defined, 373 Adenomas, 69, 151, 168 limitations of, 245 units of, 373 Adrenal cortical carcinoma, 86, 161 lung cancer, 28, 50, 74, 76, 87 Acute myocardial infarction, 95 Adriamycin, 130 lymphoma, 68, 73, 74, 76, 78 ada gene, 36, 37 Adult Health Study, 142, 150, 151, 153 mutation rates, 68-70, 96-98 Adaptive response Aflatoxins, 242 neutron RBE, 28-29, 68, 126 animal studies, 51, 52, 53, 55, 78-79, 251 Air and space travel, 3, 19 predictive value, 73, 75, 241 bacteria, 50 occupational exposures, 204 radiosensitivity, 34, 69, 71, 82-83 bystander effect and, 55 Alcohol consumption, 242 skin cancer, 74, 75, 76, 87 and cancer risk assessment, 250-251 All-Union Distributed Registry, 202 tumorigenesis, radiation-induced, 11, 12, 67, cell cycle alterations, 51, 53 Alpha particles 68-70, 73-79, 82-83, 89, 240, 241, 246 for cell lethality, 51, 52, 55, 78 and bone cancer, 87, 269 X-ray exposure, 68, 69, 100-101 in Chernobyl children, 51 bystander effect, 53-54, 55 Aniridia, 98 to chromosomal aberrations, 51, 53, 55 cell killing/lethality, 54 Ankylosing spondylitis cohorts cumulative effect of multiple low doses, 53 chromosome aberrations, 53 bone cancer, 164 DDREF and, 78-79 genetic susceptibility, 53, 87 breast cancer, 164-165, 176, 177 to DNA damage and repair, 39, 50, 51, 52, and genomic instability, 70, 71 cancer mortality, 164, 165 53, 251 internal contamination, 199-200 cohort description, 164 dose fractionation and, 78 LET value, 21 colon cancer, 164 dose-response relationships, 45, 50-53, 62, and leukemia, 71 dosimetry, 164, 165 89 and liver cancer, 68 esophageal cancer, 164 genotype and, 53 and lung cancer, 242 kidney cancer, 164 and hormesis, 333 mutagenesis, 53, 54, 68 leukemia, 164, 165, 183, 289 in humans, 50 RBE, 71 lung cancer, 164, 174 to iodine-131, 51 and tumorigenesis, 70 malignant lymphoma, 164 in lymphocytes, 51, 53 Amelogenesis imperfecta, 98 modeling cancer risk in, 287 malignant transformation as, 51-52, 62, 78- American Registry of Radiologic Technologists, multiple myeloma, 164 79 205 pancreatic cancer, 164 in mammalian cells in vitro, 51, 52, 62 Animal studies. See also specific animals prostate cancer, 164, 288 mechanisms, 11, 29, 39, 51-53 adaptive response, 78-79, 251 radiotherapy-related cancer risks, 164-165, to medical uses of radiation, 51 bone cancer, 74 174, 176, 177, 185, 287, 288, 289 in mice, 51, 52, 53, 55, 78 breast/mammary cancer, 74, 82, 83, 88 stomach cancer, 164, 185, 287, 288, 289 microarray expression studies, 39, 53 DDREF from, 77-79, 254-258 urinary tract cancer, 164, 288 385

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386 INDEX Antibody genes, 34 health end point data, 13, 76-77, 130, 131, Autoimmune hypothyroidism, 151 Antitumorigenic defenses, 67 142 Autopsy data APC gene, 66, 80, 82, 83 healthy survivor effect, 152 atomic bomb survivors, 151, 152, 153 Apert’s syndrome, 98, 103 in utero exposures, 151, 172 noncancer diseases, 151, 152, 153 Aplastic anemia, 153 incidence of cancer, 13, 130, 142, 144-145, Apoptosis, 48-49, 54, 55, 67, 80, 81, 88, 373 148-149, 151, 298-307 Apurinic-apyrimidinic endonuclease (APE1), 32, infant and childhood mortality, 8 B 33 kidney cancer, 149, 269 Apurinic nucleases, 35, 42 leukemia, 68, 72, 142, 143, 144, 153, 172, Background radiation. See Natural background Arthroses, 165 240, 244, 245, 269, 307-308 radiation Bacteria Asbestos, 200 life shortening, 153-154 Ashkenazi Jews, 85 Life Span Study, 9, 12-13, 26, 141-154, 239- adaptive response, 50 Ataxia telangiectasia, 35, 36, 79, 80, 81, 82, 83, 240, 242, 245, 246-250, 267-268, 296- DNA repair, 36, 37 tumor promotion, 241-242 86, 93 308 ATF3, 56 limitations of studies, 141, 240 Basal cell carcinoma, 66, 68, 69, 80, 84, 150- Atherosclerosis, 185, 186 liver cancer, 147, 150, 148, 149, 242, 269, 151, 167. See also Skin cancer BAX, 56 ATM gene, 67, 80, 84, 86 303-306 ATM kinase, 35, 36, 37, 39, 50, 56 lung cancer, 68, 147, 148, 150, 215, 242, Bcl2, 49 Atomic Bomb Casualty Commission, 91, 141 269, 276, 303-306 BEAR report doubling dose method for humans, 96, 123 Atomic bomb survivors lymphoma, 151, 153 Adult Health Study, 142, 150, 151, 153 medical exposure data combined with, 146- Becquerel, Henri, 2 age and cancer risks, 72, 143, 144, 145, 147, 147 BEIR I report doubling dose method for humans, 96, 97, 148, 149, 240, 297-298 mental retardation, 1 autopsy data, 151, 152, 153 mortality data, 130, 131, 141, 142, 143, 144, 118, 122, 123 benign neoplasms, 150, 151-152 145, 147, 151, 152-153, 298-307 genetic effects estimation, 94 principles of risk estimation, 138 bladder cancer, 147, 148, 269, 303-306 multiple myeloma, 151 bone cancer, 269 mutation rates, 6, 114, 129, 130-131 BEIR III report breast cancer, 12, 26, 85, 135, 147, 148-149, nervous system cancers, 148, 149, 151, 152 cancer risk models, 138 doubling dose method for humans, 118, 122- 170, 177, 180, 243, 269, 303-306 neutron RBE, 20, 27, 142, 143, 146 cancer risk assessment, 7-8, 138, 143-154, nonneoplastic disease, 13, 143, 152-153 124 239-240, 241-245, 262, 275-276, 285- nuclear industry workers compared, 201, 203 genetic risk estimates, 94, 94-95 BEIR V report, 92, 373 286, 296-308 oropharyngeal cancers, 148, 149 cardiovascular disease and stroke, 1, 8, 152, ovarian cancer, 147, 148, 149, 269, 303-306 advances in risk estimates since, 115-116, 153, 185 pancreatic cancer, 147, 148, 149 187 baseline frequencies of genetic diseases, 94- cataracts, 153 prostate cancer, 147, 148, 149, 303-306 children of, 6, 8-9, 114, 118, 129, 130-131, rectal cancer, 147, 148, 149 95, 96, 115, 117-118 149, 151 respiratory system cancers, 149 cancer risk assessment, 138, 174, 187, 246, 265, 275, 282, 283, 291-292, 299 chromosome nondisjunctions, 131 salivary gland cancer, 149-150, 269 cohort description, 13, 141, 142-143 sex differences, 144, 145, 150, 151, 153 dose-rate reduction factor, 100 n.1, 246 colon cancer, 147, 148, 149, 151, 269, 303- site-specific cancers, 147-151, 303-307 doubling dose calculation, 94-96, 100 n.1, 115, 118, 123, 124, 252 306 skin cancers, 148, 149, 150-151, 269, 295 compatibility of data with other cohorts, 267- smoking effects, 150, 276 environmental exposure studies, 208, 209- 268 solid cancers, 13, 45, 130, 142, 143, 144-147, 214 extrapolation of animal data to humans, 115 Committee’s analysis of data, 267-268, 296- 149, 245, 297-305 308 statistical analyses, 143-144 genetic disease risk estimates, 12, 94-95, 96, confounding and bias in studies, 141, 146, stomach cancer, 147, 148, 149, 150, 173-174, 115-116, 117-118, 252 leukemia model, 246, 282, 283 152-153, 268, 297 215, 240, 242, 269, 303-306 cytogenetic studies, 68 suicides, 153 multifactorial disease estimates, 95, 96, 115, data used in this study, 13, 142, 144 thyroid cancer, 148, 149, 181, 269, 295 117 mutation component, 94, 106, 115 DDREF, 246-250, 254-258 transport of risks to other populations, 14, deaths from cancer, 142, 143, 144, 145, 147, 240, 241-245, 267-268, 275-276 occupational exposure studies, 190 151 two-stage clonal expansion model applied to, Benign diseases. See also Ankylosing spondylitis cohorts; Thyroid diseases; Tinea capitis digestive system cancers, 149 262 dose-response relationships, 6, 13, 24, 45, 68, uncertainties in data, 130, 131, 141, 147, cohorts; other specific diseases 72, 137, 140, 142, 143, 144, 145-146, 172, 285-286 in adults, 162-166, 183 age at exposure and, 151 147, 149, 150, 151, 152, 153, 245 urinary tract cancer, 148, 149 dosimetry, 6, 9, 10, 20, 24, 27, 72, 129, 134, uterine cancer, 147, 148, 149, 303-306 in atomic bomb survivors, 150, 151-152 139, 141, 142-143, 144, 266 Atomic Energy Authority (UK), 190, 191, 192, breast disease, 26, 151, 163, 174, 177, 180, 185, 287 doubling dose, 7, 8, 118, 124, 130-131, 252 195, 196, 197, 198, 199, 232, 233 DREF, 146 Atomic Energy of Canada Ltd., 191, 192, 195, in children, 26, 68, 155, 156, 166-170, 174, esophageal cancer, 147, 148, 149, 215, 269 196, 197, 199 176, 177, 180, 181, 182, 183 dose-response relationship, 151 extrapolation to low dose rates, 146 Atomic Weapons Establishment (UK), 190, 191, follow-up, 8, 134, 239-240, 245 192, 194, 195, 196, 197-198, 232, 233 genetic susceptibility, 80 gall bladder cancer, 147, 148, 149, 269 ATR, 36, 37, 39 hormonal infertility, 164 neoplasms, 80, 150, 151-152 genetic risk assessment, 8-9, 91, 92, 114, Attributable risk, defined, 373 115, 118, 131, 252 Autoimmune diseases, 225 peptic ulcer, 163, 174, 175, 185

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INDEX 387 radiotherapy effects, 155, 162-167, 181, 289 Bowen’s disease, 151 lung cancer in radiotherapy recipients, 160, salivary tumors, 150 Brachytherapy, 162 174, 175 skin hemangiomas, 26, 168-169, 174, 175, Brain tumors, 80, 162, 164, 166, 167, 168, 169, in mastitis treatment group, 26, 163, 177, 176, 177, 180, 181, 183, 185 218 180, 287 thymus gland enlargement, 26, 167-168, 176, BRCA1 gene, 67, 80, 82, 83 MCF-7:W58 cell lines, 56 177, 180, 181, 182 BRCA2 gene, 80, 82, 83 medical-exposure-related risks, 12, 26, 84, tonsil enlargement, 169 Brca1 protein, 35, 36, 37, 38, 39 86, 157, 160, 163, 176-180, 286, 287 uterine bleeding, 163-164, 183 Brca2 protein, 35, 38 modeling, 148, 273 Beryllium, 200 Breakage-fusion-bridge (B/F/B) cycles, 48, 71 mortality, 170, 172, 176, 177, 243, 278, 279, Best’s macular dystrophy, 125 Breast cancer, female 280, 287, 298 Beta particles additive risk, 148 multiplicative model, 148, 163, 243 defined, 373 age at exposure and, 26, 147, 149, 160, 167, pooled analyses of data, 12, 169, 180, 243, skin cancer in mice, 75 170, 176, 180 268-269, 287 Bias. See also Confounding factors; age-specific rates, 149 protracted exposure and, 176, 180, 243 Uncertainties animal studies, 74, 82, 83, 88; see also in radiologic technologists, 205 assessment of, 139 Mammary cancer; specific animals radiotherapy-related risks, 26, 84, 86, 157, DDREF estimate, 250 in ankylosing spondylitis cohort, 164-165, 159-160, 164-165, 167, 168, 169, 174, defined, 373 176, 177 175, 176, 177, 186-187, 205, 243, 287 in epidemiological studies, 132, 133, 135- in atomic bomb survivors, 12, 26, 85, 135, 147, risk assessment, 25-26, 85-86, 148-149, 176- 136, 139, 140, 152, 173, 187, 208 148-149, 170, 177, 180, 243, 269, 287 180, 241, 243, 244, 272, 273, 275, 286, information, 135-136, 139, 208, 276 baseline lifetime risk estimates, 278 287, 293, 303-306 misclassification of disease, 139, 152-153, BEIR V model, 291-292 risk estimates, 173, 176-180, 278, 279, 280, 285 in benign breast disease cohorts, 26, 163, 282, 294 misclassification of exposure, 139, 207, 266, 177, 180, 243, 287 spontaneous rates, 26, 86 285 BRCA-type heritable, 67, 79, 80, 82, 83, 84, uncertainties in risk models, 25-26, 285 random errors, 296 85-86, 243 British Nuclear Fuels, 232, 233 reduction strategies, 140 cardiovascular disease mortality, 186-187 Bromodeoxyuridine (BrdU), 48, 60-61 selection, 135, 139, 152, 203, 208 in cervical cancer survivors, 26, 157-158, bub1, 39 systematic errors, 266, 296 176, 177 Building materials, 3 underascertainment or misclassification of chemotherapy and, 159 Bystander effects, 9, 11, 29, 37, 39, 45, 53-55, cancer incidence, 285 Chernobyl accident and, 227 62, 70, 251 Biological damage. See Chromosome childhood exposures to radiation and, 26, aberrations; DNA damage; Genetic 167, 168, 169, 172, 175, 176, 177, 180, effects of radiation; Relative biological 243, 287 C effectiveness chromosomal radiosensitivity and, 86 critical sites, 27, 29, 47, 48, 54, 74 cobalt-60 irradiation, 186-187 c-fos transcription factor, 51, 53 models, 147, 262-263 coherence of BEIR VII model with other c-jun N-terminal kinase (JNK), 55 c-jun transcription factor, 51, 53 process during energy transfer, 20, 245 studies, 287 responses to, 11; see also DNA repair contralateral, in radiotherapy recipients, 160 Californium-252, 113 mechanisms and defects; Tumorigenesis, diagnostic irradiation and, 170, 172, 176, Canadian fluoroscopy study, 176 Canadian National Dose Registry, 190-191, 192, radiation induced 177, 287 Bladder cancer. See also Urinary tract cancer dose fractionation and, 26, 170, 176-177 194, 195, 196, 198, 199, 230, 262 in atomic bomb survivors, 147, 148, 298, dose-response relationships, 74, 76, 86, 149, Canadian National Mortality Data Base, 198 Canadian nuclear workers, 192-193, 195, 196, 303-306 157-158, 159, 160, 163, 168, 170, 172, radiotherapy-related, 157, 158, 162, 163, 164 176, 178-180 197 risk models and estimates, 272, 278, 279, dosimetry, 159, 178-180 Cancer. See also Carcinogenesis; Genetic susceptibility to cancer; Tumorigenesis, 280, 282, 284, 285, 294, 303-306 epidemiological studies, 24-26, 157, 287 Bleomycin, 130 etiology, 243 radiation induced; specific sites Blindness, 98 excess absolute risk, 12, 25, 26, 149, 168, age (attained) and incidence of, 72, 143, 144, 145, 148, 149, 167-168, 180-181 Bloom’s syndrome, 93 243, 287, 305, 306 Bone cancer excess relative risk, 12, 25, 26, 148, 149, age at exposure and, 7, 26, 74, 76, 86, 143, age factors and, 264 159, 164, 175, 240, 242, 243, 244, 303, 147, 149, 150, 160, 167, 170, 176, 180, 181-182, 311 animal studies, 74 304 ankylosing spondylitis cohort, 164 in fluoroscopy cohorts, 26, 170, 176, 177, apoptosis and, 49 in cervical cancer survivors, 157 180, 243, 287, 293 baseline rates, 268, 275, 373 in childhood following in utero exposure, 1, childhood exposure and, 161, 167 genetic susceptibility, 67, 79, 80, 82, 83, 84, dose-response relationship, 74, 75, 201, 264 85-86, 87-88, 103, 243 6, 10, 112, 151, 172-173, 211, 226 genetic susceptibility, 80, 84 in Hodgkin’s disease survivors, 158, 159, data availability, 6 defined, 373 high-LET radiation and, 87, 269 176, 177 human data, 84 hormonal/reproductive factors, 76, 157-158, genes, 12, 67, 79, 80, 82, 83, 84, 85-86, 243; in nuclear industry workers, 201 159, 168, 169, 241, 243 see also Oncogenes incidence, 73, 130, 142, 144-145, 148-149, protracted exposure and, 75 hypersensitivity to radiation and, 56, 82 radiotherapy-related risks, 157, 161, 162, incidence, 148-149, 176, 177, 243, 278, 279, 151, 194-198, 200, 201, 202, 203, 298- 164, 167 280, 298, 303, 305 307 inherited predisposition, see Genetic risk models and estimates, 269, 282, 294 LET of radiation and, 24-26 Bone marrow cells, 71, 72, 74, 80, 173 leukemia in radiotherapy recipients, 159-160 susceptibility to cancer

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388 INDEX metastatic, 150 endpoints, 268-269 site-specific, 88, 241-242, 268-269, 272-273, misclassification of disease status, 139 EPA estimates, 274, 275, 282-283, 293 275, 278, 282, 283, 284, 285, 292, 303- mortality/life shortening, 2, 4-5, 28-29, 68, estimates of lifetime risk, 145, 278-286 307, 311, 312 76-77, 142, 144, 145, 151, 165, 170, 172, etiology at different histologic sites and, 241- skin cancer, 245, 270-271, 282, 294, 295 174, 175, 176, 177, 181, 189, 191, 194- 245 solid cancers (all), 144-145, 268-273, 278, 198, 200, 201, 202, 203, 204, 205, 209- examples of estimates, 310-312 279-280, 281, 282, 284, 287-289, 296, 212, 242, 243, 298-307 extrapolation from high to low doses, 50, 146 297-302, 312 multifactorial nature of, 81, 88 genetic susceptibility and, 85-87, 88, 241, stratified-background relative risk model, 299 multistep process, 75, 240, 241 251 temporal projections, 239-240, 275 registries, 13, 141, 142, 147-148, 150, 151, genomic instability and, 251 threshold models, 12, 74-75, 105-108, 120- 152, 160, 166, 202, 203, 205, 226, 268 human data for; see Epidemiological studies; 121, 124 sex differences, 7, 73, 74, 144, 145, 150, 151, Human cell lines/systems; Human studies thyroid cancer, 181, 244, 268, 270-271, 272, 161, 167, 176, 181, 244 ICRP estimates, 274, 282-283, 292-293 273, 275, 282, 286, 287 Cancer cells. See also Cell cultures; In vitro incidence data, 146, 268, 270, 271, 272, 273, time since exposure, 271, 274, 275, 289, 296 assays 278, 279, 280, 281, 283, 284, 298-302, tonsil irradiation cohort, 273 Cancer patients. See Radiotherapy studies 311, 312 total cancer, 268, 282 Cancer risk assessment. See also Atomic bomb internal exposure and, 276 transport between different populations, 85, survivors; Excess absolute risk; Excess latent period, 302 88, 240-245, 253-254, 265, 275-276, 277, relative risk; Linear no-threshold model; for leukemia, 143, 144, 173, 183-185, 244, 278-281, 284, 285, 286, 292 Linear-quadratic model; Model fitting; 245, 246, 268, 273-274, 275, 277, 278, uncertainties in, 25-26, 147, 174, 241, 244, Models/modeling; Risk assessment; 280-282, 289-290, 307-308, 309 251, 268, 272-273, 275, 276, 278, 279, specific cancer sites lifetime attributable risk, 277-286, 309-312 280, 284-286, 297, 308-310 absolute risk model, 242, 244, 245, 253-254, liver cancer, 242, 272, 278, 279, 280, 282 UNSCEAR approach, 138, 240, 268, 272, 268, 279-281, 283 lung cancer, 147, 148, 173, 174-176, 242, 274, 275, 277-278, 282-283, 293-294, adaptive response and, 250-251 244-245, 272, 275, 278, 279, 280, 282, 297-298, 307 additive model, 148, 150, 240, 241, 244-245, 286 for U.S. population, 274-284, 286 254, 276 measures of risk, 268-269, 277 Capenhurst nuclear workers, 191, 192, 195, 196 age dependencies, 143, 144-145, 147, 148, medical uses of radiation, 12, 26, 173-187, Carbon-14, 3 149, 240, 262, 268, 269, 270, 271, 273, 240, 241, 276, 286-290 Carcinogenesis. See also Tumorigenesis, 274, 275, 278, 284, 285, 286, 296, 297- method of calculating lifetime risk, 277-278 radiation induced 298, 311 model selection for this study, 6-8, 138, 269- age and, 262 alternative models, 271, 285-286, 298-302 274 Armitage-Doll model, 262 analytical approach, 269, 296-302 modifying factors and, 240, 268-269 bystander effects and, 9, 29, 54 atomic bomb survivors, 7-8, 12-13, 138, 143- mortality data, 144-145, 268, 273, 275, 278, cell cycle effects, 49, 50, 86 154, 239-240, 241-245, 267-276, 285- 280, 281, 282, 283, 298-302, 311, 312 frequency, 52 286, 296-308 multiplicative model, 148, 163, 240, 241, general mutagen model, 262 baseline incidence and mortality data, 268, 242, 243, 254, 292 genetics of, see Genetic susceptibility to 275, 278, 373 NCRP review of models, 274, 293 cancer BEIR III estimates, 138 neutron RBE and, 28-29 latent damage, 65, 68, 72, 76, 78, 159, 167, BEIR V estimates, 138, 174, 187, 265, 268, NIH model, 268, 269, 273, 277-278, 293, 215 275, 277, 282-283, 291-292, 299 294-296, 299 LET of radiation and, 24-26, 49 biologically based models, 241, 245, 262-263 nuclear industry workers, 138, 262, 268, 275, malignant transformation, 51-52, 62, 78-79, for bone cancer, 269 290 262 breast cancer (female), 25-26, 85-86, 148- parameter estimates, 268, 278, 279, 280, 284, mathematical theory of, 262 149, 163, 176-180, 241, 243, 244, 268, 285, 308-309 modifiers of, 200-201 272, 273, 275, 282, 286, 287 parametric model, 143, 299 protooncogenes, 66, 68, 80, 81-82 bystander effects and, 251 pooled analyses of data, 169, 180, 181, 243, repair of injury, 76 calculation of lifetime risk, 264-265, 266, 268-269, 273, 286 smoking and, 242 277-278, 284-286, 310-312 population modeling, 85, 88, 286 two-stage clonal expansion model, 241, 253- for children, 10, 26, 161-162, 166-170, 181, postirradiation cancer mechanisms and, 254, 262 209 241 Carcinogens cohort effects in, 297, 302 preferred (BEIR VII) model, 244, 269-278, chemical, 244 comparability of study designs and, 241 296-312 defined, 373 comparison of BEIR VII estimates with other probability of causation in, 265, 294 and genetic polymorphism, 87 sources, 282-284, 291-296 RBE and, 28-29, 146, 276, 286 Cardiovascular disease, 8 confidence intervals, 14, 278, 279, 284, 286, REID measure, 277 in atomic bomb survivors, 1, 8, 152, 153, 185 296, 299, 309 relative risk model, 25, 26, 148, 149, 159, in breast cancer survivors, 186-187 data used for BEIR VIII model, 267-268, 164, 175, 240, 242, 243, 244, 253, 279- dose-response relationships, 152, 153 277, 283-284, 296-308 281, 283, 307 genetic factors, 95, 96 DDREF adjustment, 246-250, 254-258, 274, RERF model, 269, 270, 271, 285, 286, 296, medical-exposure-related risks, 12, 159, 160, 275-276, 279, 280, 282, 283, 284, 285, 286 298, 297, 301, 302, 307 163, 185-187 dose-response functions, 245-246, 262, 269, results of calculations, 278-284 occupational exposures and, 199 274, 280, 298 Rochester thymus cohort, 26, 180, 181, 273, Case control studies, 84, 133, 134-135, 136, 148, dosimetry and, 241, 266, 268, 269, 285, 286, 292 172, 173, 190, 207, 208. See also 296 sex-specific, 267, 271, 274, 275, 278-281, Epidemiological studies; individual DREF, 146 282-283, 284, 298, 301, 311, 312 cohorts

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INDEX 389 Chernobyl accident, 224, 225, 226 Cervical cancer survivors uncertainty in data, 128, 129, 202-203 defined, 373 bone cancer, 157 urinary bladder cancer, 223, 227-228 environmental radiation exposures, 211-212, breast cancer risk, 26, 157-158, 176, 177 Chernobyl Registry, 202 224-225, 229, 230, 233, 235 dosimetry for radiotherapy, 26, 157 Children/childhood. See also Postradiation Casein kinase I and II, 39 leukemia in, 157, 158, 183, 289 generation progeny Caspase cleavage, 49 lung cancer, 157 of atomic bomb survivors, 6, 8-9, 114, 118, Cataracts (early onset), 28, 98, 112, 115, 116, lymphoma, 157 129, 130-131, 149, 151 153 rectal carcinoma, 157 benign diseases, 26, 68, 155, 156, 166-170, Cell cultures. See also Human cell lines; In vitro risk estimates, 287 174, 176, 177, 180, 181, 182, 183 assays; Lymphocytes systems; individual secondary cancers in radiotherapy cohort, 26, bone cancer, 161, 167 animal cell lines 135, 157-158, 174, 176, 177, 185 brain and central nervous system tumors, defined, 373 stomach cancer, 158, 185, 288 161, 166-167, 168-169 Cell cycle phase thyroid cancer, 181 breast cancer in women exposed during, 26, adaptive response in, 51, 53 urinary tract cancer, 157, 158 167, 168, 169, 172, 175, 176, 177, 180, and carcinogenesis, 49, 50, 86 uterine cancer, 157 243 and cell killing, 49, 50 Cervical polyps, 153 cancer risk estimates, 10, 26, 161-162, 166- and cellular response, 45, 49-50 Cervical tubercular adenitis, 169 170, 181, 209 checkpoint kinase gene, 86 Cesium-137, 114, 128, 202, 212, 213, 214, 215- Chernobyl, 51, 68, 72, 114, 128, 215-226, and chromosome aberrations, 45, 46, 48, 49, 226, 276 227, 235, 246 82 Chalk River plant, 191 CT scans, 172-173 and DNA repair, 34, 37, 39, 48-49, 50, 245- Chapelcross nuclear workers, 191 cytogenetic study, 68 246 Chemical aspects of radiation descriptive studies, 208 dose-rate effects, 49-50, 55 background radiation, 30-31 diagnostic exposures, 155, 156, 172-173, 211 dose-response relationship, 45, 50 DNA damage mechanisms, 29-30 dose-response relationships, 10, 161, 162, and genomic instability, 49, 113 electron ionization of water, 20, 21, 29-30 168, 169 and mutagenesis, 49, 50, 81, 113 in locally multiply damaged sites, 31-32 doubling doses in, 130-131 and neutron RBE, 50 oxidation reactions, 30, 31-32, 40-42, 48, 50, endocrine gland tumors, 168 and radiosensitivity, 45, 49-50, 55, 82, 83, 54 environmental exposures, 208, 209-210, 211, 86, 113 spontaneous DNA damage, 29-30 212, 213, 215-226, 229, 233, 234, 235- regulator protein, 39 Chemotherapy, additive effects of, 159, 244 238 and translocations, 45 Chernobyl accident genetic effects of radiation, 8-9, 68, 114, 118, Cell cyclin proteins, 52 adaptive response in children, 51 161 Cell killing/lethality. See also Apoptosis brain cancer, 218 in utero radiation exposure, 1, 6, 10, 112, adaptive response, 51, 52, 55, 78 breast cancer, 227 151, 172-173, 211, 226 by alpha particles, 54 case control studies, 224, 225, 226 infants, 167-168, 175, 211, 218, 226, 287 bystander effects, 9, 29, 54-55 childhood cancers, 51, 68, 72, 114, 128, 215- iodine-131 exposure, 68, 169, 173, 215 cell cycle phase and, 49, 50 226, 227, 235, 246 leukemia, 84, 161, 168, 172, 209, 210, 211, chemical modification of radiation effects, 31 chromosome aberrations, 57 212, 214, 216-222, 226-227, 233, 244 delayed, 55 cleanup (liquidation) workers, 57, 58, 60, lung cancer, 168, 175 DNA damage response disorders and, 82 114, 129, 202-204, 226, 227 lymphoma, 209, 210 dose-response relationships, 55-57, 75, 78 congenital abnormalities, 218 melanoma, 161 gene mutation and, 47 DNA damage repair indicators, 222, 228 mental retardation, 1 hypersensitivity to radiation and, 55-57 dose-response relationships, 224, 225, 226-227 mutation frequencies, 114, 128, 130-131 by low-LET radiation, 55-57 dosimetry, 114, 128, 129, 202, 203, 216-223, pancreatic cancer, 168 and lymphoma, 74, 78 224 parental preconception exposures, 8-9, 114, by neutrons, 28 Down’s syndrome, 216 130-131, 175, 214, 228-233 oocyte sensitivity, 75, 98-99, 119 ecologic studies, 215, 216-223, 226 radiotherapy-related risks, 9, 84, 161-162, in radiotherapy patients, 155 environmental exposures, 215-228, 234-235, 166-170 signal, 56 236 retinoblastoma, 161 target for, 27, 29, 74 follow-up, 202-203 risk assessment, 6, 8-9 and tumorigenesis, 12, 74, 75, 76, 82 gastrointestinal cancers, 218 salivary gland tumors, 167 Cell senescence, 72 goiter, 218 scoliosis, 172, 176, 177, 187 Cellular response. See also Adaptive response; human minisatellite loci mutations, 128-129 skin cancer, 161, 167 Cell killing/lethality; Chromosome internal exposures, 276 skin hemangioma cohort, 26, 168-169, 172, aberrations; Genomic instability, kidney cancer, 227, 228 174, 175, 176, 177, 178, 180, 181, 183, radiation induced; Germ cells; Somatic leukemia, 203-204, 216-222, 225-227 185, 287 cells lymphoma, 217, 227 soft tissue sarcoma, 161 bystander effects, 9, 29, 37, 39, 47, 53-55 mutation rates, 114, 128, 129-130 stomach cancer, 168, 185 cell cycle effects, 45, 49-50 population exposures, 114, 202, 215-228 thymus radiography cohort, 26, 167-168, hypersensitivity to radiation, 11, 32, 45, 47, registries, 202, 203 176, 177, 180, 181, 182, 243, 287, 292 51, 55-57, 82 renal cell carcinoma, 222 thyroid cancer, 68, 72, 149, 161, 162, 166, membrane damage, 29 respiratory tract cancers, 218 167, 168, 169, 181, 182, 214, 215-226, multilocus mutations, 46 risk estimates, 203-204 234, 244, 246, 287 Central nervous system cancers, 151, 161, 166- solid tumors (nonthyroid), 227-228 thyroid diseases, 169 167, 168-169 thyroid cancer, 68, 72, 203-204, 215-226, tinea capitis cohort, 68, 155, 156, 166-167, Cerebrovascular injury, 185 234-235, 246, 276 181, 182, 183

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390 INDEX tonsil enlargement, 169 Cisplatin, 34-35, 40 Consumer product radiation, U.S. population X-ray exposures, 211 Cleft lip/palate, 93, 98 exposure to, 3, 5 Cholangiocarcinomas, 150 Coal-fired power plant emissions, 3 Contiguous gene deletion syndromes, 112 Chromatid instability Cobalt-60 Cooperative Thyrotoxicosis Therapy Follow-up breaks and gaps, 47, 58 breast cancer and, 186-187 Study, 165, 166 in hematopoietic cells, 70-71, 86 chromosome aberrations, 57 Coronary heart disease, 81, 93, 106, 111 in mouse mammary epithelial cells, 71-73 and heart disease mortality in breast cancer Cosmic radiation, 3, 4, 30, 43, 204 Chromatin remodeling, 69 survivors, 186-187 Cri du chat syndrome, 93 Chromium-51, 200 LET value for electrons, 19 n.1, 21, 22, 24, Crouzon’s syndrome, 103 Chromosomal diseases, 93, 96, 117, 119 276 CS-A, CS-B genes, 80 Chromosome aberrations occupational exposure, 200 Cumene hydroperoxide, 40 adaptive response, 51, 53, 55 RBE, 24, 276 Curie, Marie and Pierre, 2 alpha particles and, 53 Cockaynes syndrome, 80 Cyclin B1, 53 aneuploidy, 48, 49, 69, 70, 83, 130, 131 Cohort studies, 133, 134. See also Atomic bomb Cyclin-dependent protein kinase catalytic breaks, 51 survivors; Radiotherapy studies subunit, 127 and breast cancer, 86 Colon cancer Cyclodeoxynucleosides, nucleotide-excision bridge formations, 45, 47, 48, 71 in atomic bomb survivors, 147, 148, 149, repair, 32, 34-35 bystander effect, 53, 54, 55 151, 269, 303-306 Cyclophosphamide, 130 cell cycle stage and, 45, 46, 48, 49, 82 baseline lifetime risk estimates, 278 Cystic fibrosis, 8, 93 centric rings, 45, 57, 58 chromosome aberrations and, 86 Cytochrome c, 49 centrosome defects, 48, 49 genetic susceptibility, 66, 67, 79, 80, 86-87 Cytogenetic studies, 68 Chernobyl accident and, 57 hereditary nonpolyposis, 79 Cytokines, 54 and colon cancer risk, 86 incidence, 278, 279, 284, 298, 303, 305 complex exchanges, 46, 48, 67, 68 mortality, 278, 280, 282, 298, 304, 306 delayed, 54 in radiologists and radiologic technologists, D deletions, 29, 30, 35, 46, 68, 69, 93 205 detection methods, 45-46, 57 in radiotherapy recipients, 163, 164, 288 Dally, Clarence, 2 dicentric exchanges, 24, 25, 28, 45, 46, 57, risk models and estimates, 272, 275, 278- Danish Cancer Registry, 160, 205 Deaf mutism, 98 58, 71 280, 282, 284, 287, 288, 294, 303-306 diseases arising from, 82, 93, 96 Colorectal cancer, 80, 82, 161 Death certificates, reliability of data from, 142, DNA repair defects and, 45-46, 57, 65 Combined UK Industrial Workforce study, 200 150, 152-153, 208, 303 Defense Radiological Protection Service dose fraction and, 57 Committee of the British Medical Research dose-response relationship, 24, 25, 45-46, 57- Council, 91 (British), 190 59, 60-61, 73, 74, 256, 257 Compton scattering, 20, 22 Delayed lethality, 47 Dementia, 153 frequencies, 46, 47-48 Computed tomography (CT) scans, 4-5, 156 and genomic instability, 46, 47-48, 49, 54, Computer monitors, 3 Dental radiography, 156 58, 59, 60-61, 70, 251 Confounding factors Dentinogenesis imperfecta, 98 Denys Drash syndrome, 80 gross loss events, 66 in atomic bomb survivor studies, 141, 146, heritable fragile sites, 69 152-153, 268, 297 Development. See Growth and Development in human lymphocytes, 24, 25, 28, 45, 46, birth cohort effects, 297, 302 effects Diabetes mellitus, 8, 93, 111, 113 51, 53, 57, 58, 59, 61, 86 chemical exposures, 233 inversions, 48 control of, 138 Diagnostic radiography. See also Medical uses of late effects, 24 country differences in baseline cancer rates, radiation adults, 170-172 LET dependence, 45 268 in mammalian cells, 45 defined, 133 angiography, 156 in mammary epithelial cells, 61, 71 in ecologic studies, 207 and breast cancer, 170, 172, 176, 177 cancer mortality risk, 4-5, 68, 170, 176 mechanisms of induction, 45-46, 74 healthy worker/survivor effect, 136, 152, microsatellite sequence instability, 68, 72 189, 194, 205 children, 155, 156, 172-173, 211 monocentric exchanges, 45; see also lifestyle-related, 57, 138, 198, 199, 240 CT scans, 4-5, 155, 172 cumulative doses, 156 Translocations occupational exposures, 136, 189, 194, 198, neutron RBE and, 28 199-200, 205 dosimetry, 155, 156, 170, 176 nondisjunctions, 131 socioeconomic status, 198 fluoroscopy for pulmonary tuberculosis follow-up, 155, 170-171, 174, 175, 176, in plant cells, 45 species variation in susceptibility, 73 proximity effects, 45 stress, 71 177, 187 rate of formation, 46 Congenital disorders in utero exposures, 172-173 interventional procedures, 156 RBE and, 24, 27-28, 276 Chernobyl accident and, 218 saturation effects at high doses, 45 doubling dose, 131 iodine-131 exposures, 171, 173, 234 spontaneous, 53 environmental radiation exposures and, 211, and leukemia, 170, 171, 172 limitations of studies, 187 telomere-associated instability, 71-73 229, 230, 232, 233, 235 trisomy, 93 frequencies, 112 and liver tumors, 68 and tumorigenesis, 24, 46, 48, 66, 68-69, 70, in mice, 115, 116, 131 and lung cancer, 170, 174, 176 and lymphoma, 171 72-73, 74, 82, 86 multifactorial nature of, 93, 95, 96, 112, 117 Chromosomes mutation component, 105-106, 111, 116 mammography, 4, 20, 21, 22, 24 basic concepts, 327 PRCF, 111 photon energies, 20 radioisotope studies, 156 human, 5, 11, 21, 58, 59, 61, 93 risk estimates, 115, 116, 117, 120 Cigarette smoking. See Smokers/smoking Connexin, 43, 54 scoliosis, 155, 172, 176, 177, 187

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INDEX 391 techniques, 156 cell cycle phases and, 34, 37, 39, 48-49, 50, skin erythema, 2 Thorotrast exposure, 68, 150 245-246 units, xi, 2 and thyroid cancer, 171, 234 and cell lethality, 82 variability within populations, 207 uncertainties in risk estimates, 286 in chick cells, 36 weighting factor, xi, 142, 143, 204, 275-276, X-rays, 3, 4, 5, 6, 21, 22, 156, 171, and chromosomal aberrations, 45-46, 57, 65 378 286 cross-overs, 32, 80 Dose and dose-rate effectiveness factor Diamide, 40, 42 of cyclodeoxynucleosides, 34-35 (DDREF) Digestive system cancer. See also Colon cancer; dose-rate effects, 49, 56 for acute doses, 60 Esophageal cancer; Rectal cancer; of double-strand breaks, 32, 34-35, 36-39, adaptive response and, 78-79 Stomach cancer 42, 45-46, 47, 49, 51, 65, 73, 81, 87 from animal studies, 77-79, 246, 254-258 in atomic bomb survivors, 149 fast reaction, 35-36 applications, 44, 282 risk estimates compared, 282, 292, 294 and gene amplification, 47 for atomic bomb survivors, 246-250, 254-258 secondary, in radiotherapy patients, 159 genes, 36, 37, 39, 40, 42, 71, 86, 87-88 bias and variance of sample estimate of, 250 DIR1 gene, 52, 56 and genetic susceptibility to cancer, 71, 79- calculation, 44-45, 254-258 DNA amplification, 48 81, 87 cancer risk assessment, 246-250, 254-258, DNA-binding proteins, 34 and genome instability, 48, 49, 72 274-278, 282, 309 DNA concepts, 327, 374 and growth and development, 34 from cellular and molecular studies, 246, 256 DNA damage Holliday junction, 36, 38 defined, 246, 248, 374 adaptive response to, 39, 50, 51, 52, 53 homeologous recombination, 36, 245-246 derivation by Bayesian analysis, 246-250, base removal, destruction, or mutation, 29, homologous recombination, 32, 35, 36, 38, 254-258 30, 31, 32, 46, 54 49 and dose-response relationship, 44-45, 60, and cancer risk, 239 hypersensitivity to radiation and, 56, 71, 239 246-250, 254-258 chain breakage, 30, 46 inducible, 36-39 extrapolation of high to low dose rates, 44, chemically induced, 34-35 of locally multiply damaged sites, 27, 31, 34, 247 Chernobyl accident and, 222, 228 35, 36 gamma rays, 61 and chromosome aberrations, 45 loss-of-function mutations, 67 genetic risk assessment, 92, 246 dose-response relationship, 31, 73, 246-247 in mammalian cells, 35, 36-37 ICRP value, 246, 282, 293, 297 double strand breaks, 29, 30, 31, 45-46, 48, microhomology-mediated, 38 for mutagenesis, 246 52, 65, 70, 73, 245 of mismatches, 34, 80 rationale for, 247 free radicals and, 19, 29-30, 239 molecular mechanisms, 32-39 for tumorigenesis, 77-79, 246-250 internucleosomal digestion of DNA, 49 nonhomologous end joining, 29, 32, 35-36, uncertainties in, 279, 284, 285, 286, 295, LET of radiation and, 26-27, 31, 62 40, 42, 46, 47, 48, 68, 70, 71, 80, 87, 245 296, 310 lethal, 31, 35, 42 normal processes, 32 UNSCEAR value, 131, 246, 249 locally multiply damaged sites (clustered nucleotide-excision, 32, 34-35, 87 Dose effectiveness factor (DEF), 44, 246 damage), 26-27, 31-32, 34, 46, 48 oxidative processes and, 31-32, 40-42, 48 Dose fractionation. See also Diagnostic low vs high dose and, 9-10, 31, 45, 46 radiation resistance and, 49 radiography measurement, 31 and radiosensitivity, 32, 34, 37, 40, 56, 69, adaptive response, 78 mechanisms, 29-30, 26-27, 29-32, 62 71, 80, 82, 83, 87, 239 and breast cancer risk, 26, 170, 176-177 mutagenic, 35, 40, 65, 112 of refractory, complex breaks, 35, 36 and chromosome aberrations, 57 natural background radiation and, 30-31 signal transduction pathways, 32, 34, 36-39, defined, 374 oxidative, 19, 30-32, 34, 40-42, 50 48, 49, 54, 80 and dose-response relationship, 44, 55, 73, prevention, 29-30, 34 of single-strand breaks, 32, 34, 56, 80 74, 75-76 probability from energetic electrons, 26-27 slow reaction, 35, 36 and hypersensitivity to radiation, 55 protracted, low-dose exposure and, 31 in somatic cells, 36 kinetics, 75-76 proximity-promoted interaction of lesions, 45 spontaneous vs. induced damaged, 31, 34 and leukemia risk, 73 and radiosensitivity, 32, 34, 37, 56 track of radiation and, 10, 43-44 and lung cancer risk, 176 resonance phenomenon, 29-30 and tumorigenesis, 6, 11, 65, 68, 69, 70, 73, and mutagenesis, 57 sensors, 31, 50, 56, 69, 86 82, 83, 227-228, 239, 246 and mutation rates, 99 signaling presence of, 36, 50, 65 xeroderma pigmentosum patients, 79, 80, 81 and tumorigenesis, 68, 73, 75-76, 78-79, 182 single-strand breaks, 29, 30, 31 in yeast, 30, 36, 40-42 Dose rate spontaneous vs. induced, 30, 31, 34 Dogs, life-span shortening, 76 and chromosome aberrations, 24 strand invasion, 38 Dose. See also Absorbed dose; Effective dose; defined, 374 time dependence, 46 Equivalent dose, defined; Low doses and dose-response relationship, 73, 74 track characteristics and, 10, 45 combining low- and high-LET radiations, 2, extrapolation from high to low dose, 50 from X-rays, 30, 32, 33, 36 3, 199 and mutation rate, 100 n.1 DNA-DNA covalent cross-links, 30 conversion factors, xi in radiotherapy patients, 156-157 DNA ligases, 32, 33, 34, 35 defined, 374 and RBE, 24 DNA-membrane complex, 29 estimating, 137, 166, 203, 207, 266; see also reduction factor, 100 n.1, 116, 130-131 DNA-PK, 35, 36, 39, 42, 71 Dosimetry of ionizing radiation and tumorigenesis, 73, 74 DNA-protein covalent cross-links, 30 extrapolation of high to low, 9, 29, 44, 50, Dose-rate effect DNA radical, 29 54, 62, 146, 296 cell cycle phase and, 49-50, 55 DNA repair mechanisms and defects of internally deposited radionuclides, 3, 4 defined, 374 animal studies, 34, 36, 42, 52, 69, 71 linear-quadratic function, 143 DNA repair defects, 49, 56 in bacteria, 36, 37 organ, 4, 143 inverse, 49-50, 55, 57, 60 base-excision, 32-34, 51, 53, 80, 87 population, 207 life shortening, 77 bystander effect, 54 priming, 51-53, 55, 78 protracted dose distinguished from, 77

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392 INDEX Dose-rate effectiveness factor (DREF) mutations, 47, 50, 57, 59-60, 61, 73, 108, BEIR V estimates, 12, 94-96, 100 n.1, 115, for solid tumors, 146 113, 114, 245, 246 118, 123, 124 Dose-response relationships. See also noncancer mortality, 152, 153 children of atomic bomb survivors, 130-131 Radiosensitivity occupational exposures, 189 chromosomal diseases, 96 adaptive response and, 45, 50-53, 62, 89 ovarian cancer, 12, 50 chronic multifactorial diseases, 12, 115, 119 animal models, 73-75, 89, 245, 246, 249, quadratic, 74 defined, 8, 93, 111 255, 256 radiotherapy-related cancers, 157-170 dose rate and, 130-131 assessment of, 139, 140 sex differences, 73, 74 end points, 122, 123, 124, 130-131 atomic bomb survivors, 6, 24, 45, 68, 72, signal transduction pathways and, 62 equation, 8, 101-102, 115 137, 140, 142, 143, 144, 145-146, 147, single-tracks with repair factor, 44-45 estimation, 8, 93-94, 97-101, 113, 115 149, 150, 151, 152, 153, 245, 256 skin cancer, 74, 76, 151, 245 ESTR mutations, 126 Bayesian statistical analysis of, 246-250, solid tumors, 74-75, 142, 144, 145-146, 201, extrapolation from mice to humans, 96-97, 254-258 245, 298 109-111, 252 benign neoplasms, 151 temporal relationships, 45, 50, 60, 61-62, 68, first-generation mortality and, 130 biophysical modeling, 45, 139, 246 70, 73-77, 245-246 gametic, 130 bone cancer, 74, 75, 201 threshold model, 12, 74-75 Mendelian diseases, 12, 94-95, 115 breast cancer, 74, 76, 86, 149, 157-158, 159, thyroid cancer, 149, 160, 162, 167, 168, 169, minimum, 130 160, 163, 168, 170, 172, 176, 178-180 182, 215, 224, 225, 276 mouse vs human mutation rates, 12, 96-101, bystander effect and, 45, 53, 54-55 thyroid diseases, 153 113, 119, 122-124 cancer mortality, 145 translocations, 57, 58, 60, 61 multifactorial diseases, 95-96 for cancer-risk assessment model, 245-246, in tumorigenesis, 12, 45, 50, 55, 59, 60, 61- mutation component, 8, 101-105, 113, 117 262, 269, 274 62, 68, 73-77, 84, 89, 140, 245-246 in nuclear test site populations, 128 cell cycle phase and, 45, 50 in tumor-suppressor gene disorders, 84 radiation-induced mutation rates, 99, 101, cell killing/lethality, 55-57, 75, 78 uncertainties in, 246 119 Chernobyl accident and, 224, 225, 226-227 X-rays, 49, 56, 61, 62 reciprocal, 93 in children, 10, 161, 162, 168, 169 Dosimeters, personal, 189, 193-194, 201 spontaneous mutation rates, 8, 96-101, 119, chromosome aberrations, 24, 25, 45-46, 57- Dosimetry of ionizing radiation. See also 122, 123 59, 60-61, 73, 74, 256, 257 Microdosimetry uncertainties, 98-99, 130, 131 chronic exposure, 43 ankylosing spondylitis cohort, 164, 165 UNSCEAR estimates, 96, 122, 123, 124 control population, 43 atomic bomb survivors, 6, 9, 10, 20, 24, 27, zygotic, 96, 102, 113 DDREF and, 44-45, 60, 246-250, 254-258 72, 129, 134, 139, 141, 142-143, 144 Down’s syndrome, 93, 216, 244 DNA damage and response, 31, 73, 246-247 and breast cancer, 159, 178-180 Dpc4 gene, 69 dose fractionation and, 44, 55, 73, 74, 75-76 and cancer risk assessment, 241, 266, 268, 269 Drosophila melanogaster, 53, 91 dose rate and, 73, 74 cervical cancer treatment cohort, 26, 157 Duchenne’s muscular dystrophy, 93 environmental radiation exposures, 224-225, Chernobyl accident, 114, 128, 129, 202, 203, Duodenal ulcer, 153 233, 234, 235 216-223, 224 in epidemiological studies, 132, 137, 139, defined, 374 140, 189, 208, 245, 246 diagnostic radiation, 155, 156, 170, 176 E extrapolating from high dose to low dose, 44- DS02 system, 27, 142, 269, 285, 296 45 DS86 system, 27, 142, 285 Edison, Thomas, 2 Effective dose general aspects, 43-45, 73 fallout from nuclear weapons testing, 212, genomic instability and, 45, 46, 48, 49, 60-61 213, 214 background radiation worldwide, 43 hypersensitivity to radiation and, 55-57 fluoroscopy studies, 170, 176 defined, 374 by source of radiation, 22-24 for internally deposited radionuclides, 43, 276 natural background radiation, 228 iodine-131 exposure, 235, 276 neutron component, 27, 143-144 Electricité de France, 191, 192, 197 LET of radiation and, 9, 24, 43, 45, 126, 158, nuclear-facility-related population exposures, Electromagnetic radiations. See Gamma rays; X- rays 245 209-211, 212, 213, 214, 229-232 leukemia, 71, 72, 73-74, 76, 77, 142, 144, nuclear industry workers, 60, 138-139, 190, Electrons 157, 158, 160, 161, 163-164, 165, 183, 191, 192, 193, 198-199, 201, 202, 203, binding energy, 20 hydrated, 29-30, 54 184, 245, 264, 295 231, 233, 290 life shortening, 76-77, 89, 249, 255, 257, 258 postpartum mastitis study, 163 ionization of water, 20, 21, 29-30 linear, 13, 47, 60, 62, 73, 74, 77, 137, 201, radiotherapy recipients, 164, 165 LET, 19, 20 penetration depth, 21 246, 247, 250, 264, 269, 299 uncertainties in, 3, 14, 128, 129, 139, 142, linear no-threshold, 246 169, 198-199, 233, 241, 266, 285 secondary, 27, 29, 31 linear-quadratic, 7, 24, 43-44, 47, 74, 201, Doubling dose Endocrine glands, cancer of, 168 Endometrial carcinoma, 67, 80, 86 247-248, 250, 255, 257, 274, 280 acute, 60, 122 liver cancer, 150, 201 advances in methodology, 94-101, 119, 122- Energy transfer process at low doses, 10, 43-45, 57-62, 73 124 biological damage process, 20 direct effects, 26 lung cancer, 74, 76, 158, 160, 163, 201, 255, atomic bomb survivor data, 7, 8, 118, 124, 262 130-131, 252 indirect effects, 29-30 in lymphocyte assays, 57, 58, 60 baseline frequencies of genetic diseases, 94- of low-LET radiation, 20-21 Environmental radiation exposures lymphoma, 73, 74, 77, 78, 151 96, 115 maxiumum likelihood estimates, 250 basis for, 8, 96, 122-124 from atmospheric releases, 212-215 modifying variables, 264-266 BEAR Committee estimates, 96, 123 cancer incidence and/or mortality, 209-212 case control studies, 211-212, 224-225, 229, mouse studies at low doses, 58, 60, 73-75, BEIR I estimates, 96, 97, 118, 122, 123 76, 78, 126 BEIR III estimates, 118, 122-124 230, 233, 235

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INDEX 393 cesium-137, 215 interpretation of data, 139-140, 141 site-specific cancer in atomic bomb Chernobyl accident, 215-228, 234-235, 236 of LET-related risks, 24-26 survivors, 147-150 children, 208, 209-210, 211, 212, 213, 215- linear relative risk model, 137, 138-139 site-specific cancers, 303-304 226, 229, 233, 234, 235-238 measurement errors, 139, 266 skin cancer, 148 cohort studies, 212, 213-214, 229, 231-232, measures of association, 132, 137 solid cancer mortality, 145 235 meta-analyses, 139-140, 268 statistical precision, 137-138 congenital defects, 211, 229, 230, 232, 233, nuclear industry workers, 189, 190-193 stomach cancer, 12, 287, 288, 289, 301-302 235 pooled analyses of data, 169, 180, 181, 243, stratified baseline risks, 299 dose-response relationships, 224-225, 233, 268-269 thyroid cancer, 12 234, 235 randomized intervention trials, 133-134 uncertainty in, 285-286 ecologic studies, 208-211, 212, 215, 216-223, retinoblastoma, 84 Expanded simple tandem repeat (ESTR) loci, 228-229, 235, 236-237 statistical power, 136, 189, 204, 208, 241, 113-114 fallout from weapons tests, 212-215, 234, 245 Experimental studies 235 tools of statistical inference, 137-138 defined, 133 iodine-131, 215, 233-236 types, 133 potential disease phenotypes, 112-113 and leukemia, 209, 210, 211, 212, 214, 216- uncertainty in, 133, 207, 208, 265 RBE of neutrons, 28-29 222, 226-227, 228-229, 230, 231, 232, Epidermal growth factor receptor (EGFR), 55 spontaneous vs. induced mutations, 124-125 233, 235 Equivalent dose, defined, 374 Exposure to ionizing radiation. See also limitations and weaknesses of studies, 207- Escherichia coli, 36 Dosimetry of ionizing radiation; 208, 233, 235 Esophageal cancer, 147, 148, 149, 164, 170, 215, Environmental radiation exposures; Low and lymphoma, 209, 217, 228-229, 230, 231 269, 282, 294 doses; Occupational radiation exposure; natural background, 3, 4, 8, 31, 43, 209, 228, Ethylnitrosourea (ENU), 69 Protracted exposure 236-237 Etoposide, 130 annual worldwide, from natural sources, 2, 3, nuclear facility proximity and, 208-212, 229, age at exposure and, 149 4 230, 233, 234, 235-236 European Childhood Leukemia-Lymphoma atomic bomb survivors, 6, 9, 129, 139, 141 parental preconception, 211, 212, 215, 228- Incidence Study, 226 chronic, 11, 43, 56, 68, 129, 280 233, 235, 237 Excess absolute risk (EAR), 269, 270, 271, 272, CT scans, 4-5 and reproductive outcomes, 211, 229, 231, 273, 274, 275, 276, 277 defined, 374 232, 233 age at exposure, 298, 301 factors affecting, 4 surrogates for, 207 application, 137, 143, 240-241 high-dose, 4, 9, 141 Three Mile Island accident, 208, 209, 211 breast cancer, 12, 25, 26, 149, 168, 243, 287 hypoxic conditions, 34 and thyroid cancer, 215-226, 234, 236 comparison of alternative models, 300 limits, 5, 43 uranium mines, 211 defined, 132, 137, 143, 374 misclassification, 139, 207 Epidemiological studies. See also specific leukemia, 144, 307 priming dose, 51-53, 55, 78, 251 cohorts linear dose-response function, 299 scenarios, 4-6 analysis of data, 136-139 parametric model, 306 surrogate indicators, 207, 208 assessment of associations, 132-133, 139-140 model fitting, 296, 299, 304-306 uncertainties in data, 3, 139, 174 BEIR V principal environmental studies, modeling, 143, 285-286 U.S. population, 3-4 208, 209-214 site-specific cancer in atomic bomb whole body scans, 4-5, 141 bias, 132, 133, 135-136, 139, 140, 152, 173, survivors, 147, 149, 304-306 Extrapolation of data 187, 208 solid cancer mortality, 145 from animals to humans, 73, 96-98, 109-111, Bradford Hill criteria, 140 tumorigenic radiosensitivity, 84 114, 115, 252 breast cancer, 24-26, 157 uncertainty in, 285-286 BEIR V report, 115 case control, 133, 134-135, 136, 148, 172, Excess relative risk (ERR), 144, 268, 269, 271, cross-population, 85, 88, 240-245, 253-254, 190, 207, 208 272, 273, 274, 275, 276, 277 265, 266, 275-276, 278-281, 284, 285, childhood cancer, 173, 208 age at exposure and, 148, 285-286, 296, 297- 286, 292 cohort, 133, 134, 135, 136, 173, 207, 208 298, 299, 300, 301 from high dose to low dose, 9, 29, 44, 50, 54, comparability in study design, 133, 135-136, application, 137, 143, 240 62, 146, 247, 296 241 bias and, 152 from in vitro to in vivo transformation confounding, 133, 136, 138, 141, 199-201, breast cancer, 12, 25, 26, 148, 149, 159, 164, systems, 52, 53 207, 240 175, 240, 242, 243, 244 Moolgavkar and Knudson two-stage clonal control group, 134, 136, 204 coherence of BEIR VII estimates with other expansion model, 241, 253-254 data collection, 133-136, 208 estimates, 287-288 postirradiation cancer mechanisms and, 241 defined, 132, 374 comparison of alternative models, 300 descriptive, 207, 208 defined, 132, 137, 143 n.3, 374 design issues, 135-136, 187, 198, 207-208, follow-up period and, 297 F 287 in heritable retinoblastoma patients, 84 dose-response relationships, 132, 137, 139, leukemia, 12, 295, 307-308 FA-A to FA-C genes, 80 Fabry’s disease, 93 140, 189, 208, 245, 246 linear dose-response function, 299 ecologic design, 10, 207, 208, 215, 216-223, liver cancer, 148, 301, 302 Fallout. See Nuclear weapons testing 226 lung cancer, 12, 148, 150, 159 Familial adenomatus polyposis, 67, 80, 82, 83, 98 exposure assessment, 134-135, 137, 139, model fitting, 296, 299-301 193-194, 207 excess relative risk, 132, 143, 285-286 Familial hypercholesterolemia, 98, 125 extrapolation of risks from, 240-241 for radioepidemiological tables, 306 Fanconi’s anemia, 80 Fbxw7 gene, 69 high-dose studies, 139 RERF, 301 hybrid (“nested”), 135, 148, 190 sex-specific, 287, 301 FEN-1 structure-specific nuclease, 32, 33, 38

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394 INDEX Fenton oxidants, 30 epigenetic silencing events, 66, 67 heritability concept, 121-122 Fernald facility, 191, 200 functional polymorphisms, 12, 86-88, 113, 114 at human minisatellite loci, 126, 128-130 Fetal exposure to radiation gatekeeper, 66-67, 69, 81 indicators of risk, 8, 118 atomic bomb survivors, 151 haploinsufficiency, 125 models of multifactorial diseases, 120-122, and cancer in childhood, 6 human counterparts in mice, 98-99 252 IEER issues, 330 interactions (epistasis), 12, 70, 108 multifactorial threshold model, 120-121, 252 and mental retardation, 1 low-penetrance, 85-88 Genetic risk assessment. See also Mutation Fifteen-Country Workers Study, 336 oxidative damage resistance, 40-42 component of genetic diseases Finite-locus threshold model, 105-108, 124 proto-oncogenes, 81-82 advances since BEIR V, 115-116 Fluorescence in situ hybridization (FISH) radiation resistance, 30, 40-42 in atomic bomb survivors, 8-9, 91, 92, 114, method of chromosome painting, 45-46, radiation-responsive, 39 115, 118, 131, 252 57 recoverability of induced mutations in live autosomal dominant disorders, 94, 111, 115, Fluoroscopy births, 109-111, 124, 125 116, 117 and breast cancer, 26, 170, 176, 177, 180, 243 tumor-supressor, 39, 65, 66, 69, 80, 80, 81 autosomal recessive diseases, 94, 112, 115 Canadian epidemiological study, 176, 287 X-linked HPRT, 47, 54 back calculation, 94, 117 dosimetry, 170, 176 Genetic diseases. See also Genetic susceptibility baseline disease frequencies, 12, 94-96, 115, and lung cancer, 174, 175, 176, 288, 289 to cancer; specific diseases 117, 252 Massachusetts tuberculosis cohort, 170-171, absolute risk, 110 bases for, 8, 96, 115-116 174, 176, 243, 273, 287, 292 autosomal dominant, 79, 80, 81, 92, 94, 95, BEIR III estimates, 94-95 and skin cancer, 2 96, 97-98, 101, 102, 103-105, 110, 112, BEIR V estimates, 12, 94-95, 96, 115-116, 14-3-3 proteins, 39 115, 116, 117, 125 117-118, 252 Free radicals, DNA damage from, 19, 29-30, 239 autosomal recessive, 79, 80, 81, 92-93, 94-95, calculations, 109, 115, 116 French Commissariat a l’Energie Atomique, 28, 96, 101, 104, 105, 110-111, 115, 117-118 chromosomal diseases, 115, 117 190 baseline frequencies, 12, 92, 94-95, 96, 115, chronic multifactorial diseases, 115, 116, 117 117-118 by class of disease, 94, 117 basic concepts, 328 congenital abnormalities, 115, 116, 117, 120 G chromosomal, 93, 96, 115, 119 current estimates, 116, 118-120 chronic, 111, 115, 116, 119 DDREF and, 92, 246 GADD45 gene, 39 congenital, 93, 95, 105-106, 112, 115, 117, 119 direct method, 8, 112 Gall bladder cancer, 147, 148, 149, 269 defined, 92 doubling dose method, 8, 12, 93-101, 102, Gamma rays experimental data, 112-113 111, 115, 117, 118, 119, 252 bystander effects, 54-55 frequency, 105 endpoints, 118, 130, 131 cancer risk estimates, 276 inborn errors of metabolisms, 113 equilibrium effects, 94, 117 carcinogenesis, 24-26, 28 marker, 125 extrapolation of animal data to humans, 96- cobalt-60, 19 n.1, 21, 22, 24 Mendelian, 92-93, 94-95, 96, 98, 105, 111, 97, 109-111, 114 damage mechanisms, 26-27 112, 113, 115, 119 first postradiation generation, 94, 116, 117, DDREF, 61 MIM maps, 125 118 defined, 374 minisatellite polymorphisms and, 113, 114 framework, 92 dose-rate effect, 28 multifactorial, 8, 93, 95, 96, 101, 112, 115, germ cell stages and, 92 dosimetry for atomic bomb survivors, 6, 142 117, 119 goal, 92 environmental exposures, 212 multisystem developmental abnormalities, indirect method, 8, 93-94 extrapolation to X-ray exposures, 24 12, 112 methods, 91, 92 high-energy, 24 mutation component, 98, 101-105, 117 mouse data, 92, 96-97, 98-101, 109-111, mutations in mice from, 126 potential phenotypes, 111-113 112-113, 114, 115-116, 252 occupational exposures, 204 PRCF estimates, 110-111 mutation component, 12, 81, 94, 101-113, photon energies, 19, 20, 21, 22, 24, 276 prevalence, 80, 96, 98, 110 115, 116, 117, 119, 252 RBE, 21, 22, 24, 25, 28, 126, 276 “radiation-inducible,” 92 overlap in estimates, 119-120 signal transduction study, 56 risk estimation by class of, 94, 115, 116 potential recoverability correction factor, 12, terrestrial, 30 spontaneous mutation rates, 97-98, 109 109-110, 115, 119, 252 Gap junctions, 39, 54, 55 sporadic cases, 108 reconciliation of present and past estimates, Gastric ulcer, 153, 241 UNSCEAR estimates, 94-95, 96 117, 118 Gastrointestinal cancers, 218 X-linked, 92, 93, 94, 95, 96, 97, 98, 101, reproductive outcomes, 252 Gene amplification, 47, 49, 72 104-105, 110, 115, 116, 125 second-generation progeny, 116 Gene transcription, 55, 113 Genetic effects of radiation. See also sex differences, 119, 120 Gene-environment interactions, 12, 86, 87, 88 Chromosome aberrations; DNA damage; spontaneous mutations, 8, 96-101 Genes. See also specific genes Mutations UNSCEAR estimates, 92, 94, 95, 96, 109, antibody, 34 animal studies, 12, 68-70, 73, 82-83, 92 111, 112, 115, 118 autosomal recessive disorders, 80 background data from humans, 8 X-linked disorders, 94, 111, 115, 116, 117 basic concepts, 327 basic concepts, 328 Genetic susceptibility to cancer. See also breast cancer, 67, 79, 80, 82, 83, 84, 85-86, BEIR I estimates, 94 Radiosensitivity; Tumorigenesis, 243 cardiovascular disease, 95, 96 radiation induced caretaker, 67 in children, 8-9, 68, 114, 118, 161 age of onset in carriers, 81 checkpoint kinase, 86 detection, 8 alpha particles and, 53, 87 deletions, 11, 58, 61, 66, 67, 86, 109, 110, disease liability concept, 107, 120-121 animal studies, 68-70, 71, 73, 82-83, 87-88, 111, 112, 119, 124, 125 germ-cell mutations at ESTR loci and, 113- 89 DNA repair, 36, 37, 39, 40, 42, 71, 86, 87-88 114, 125-130 autosomal dominant disorders, 66, 79-81, 85

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INDEX 395 autosomal recessive disorders, 79, 80, 85 transgenerational, 127 defined, 375 breast cancer, 67, 79, 80, 82, 83, 84, 85-86, and tumorigenesis, 39, 46, 48-49, 65, 67, 69, dose units, xi, 2 87-88, 103, 243 70-73, 78, 251 dose-rate effects, xi and cancer risk assessment, 85-87, 88, 241, in zygotes, 127 epidemiological studies, 198-199 251 Genotype, and adaptive response, 53 mutation rates, 9, 126 cancer-prone human disorders, 79-81, 85 Germ cells. See also Genetic diseases; Genetic physics and dosimetry, 19, 198-199 cellular mechanisms, 79, 81-82 susceptibility to cancer RBE, 31, 126 children, 161 defined, 374 sources, 4 colonic and other neoplasms, 66, 67, 79, 80, ESTR loci, 113-114, 125-130 Hiroshima Tumor Registry, 268 86-87 minisatellite loci, 113-114, 128-129 Histones, 30, 31 DNA repair defects and, 71, 79-81, 87 mutations, 6, 8, 81, 97, 109, 113-114, 125- hMre11/hRad50/Nbs1 DNA-binding and genes of low penetrance and, 85-88 130 exonuclease complex, 35, 36, 39 heritable radiosensitivity and, 82-85 polymorphisms, 87 Hodgkin’s disease, 12, 130, 151, 158-159, 174, human data on, 83-87 stages and radiation conditions of relevance, 175, 176, 177, 242-243 leukemia, 80 92 Hormesis, 11 low-penetrance genes, 85-89 German Childhood Cancer Registry, 226 adaptive response, 333 lymphoma, 80 Gliomas, 55, 82, 166, 168 animal studies, 334 mutations, 66-67, 73, 81, 113 Glycosylases, 32, 34, 35, 42 cell studies, 333 population modeling, 85, 88 Goiter, 218, 226, 244 and epidemiology, 334-335 proto-oncogenes and, 79, 80, 81-82 Grave’s disease, 165, 166 life span data, 334 risk modeling, 81-82, 85, 86, 88, 120-122, Growth and development effects theoretical considerations, 332 251 animal studies, 115 tumor incidence data, 334 secondary cancer in radiotherapy patients, DNA repair defects, 34 Hormones 161 human studies, 8 and breast cancer, 76, 157-158, 159, 168, skin cancer, 79, 80 mental deficiency, 112 169, 241, 243 species variation in, 73 multisystem abnormalities, 112, 115 and thyroid cancer, 244 spontaneously arising human tumors, 66-67 Guardian-of-the-genome hypothesis, 48-49 and tumorigenesis, 75 strengths and weaknesses of current HPRT gene, 44-45, 47, 51, 53, 54, 58, 61 estimates, 118-120 hRad51 protein, 35, 36 thyroid cancer, 80, 81-82, 244, 246 H hRad52 protein, 35, 36 tumor suppressor genes and, 79, 80, 81 hRad54 protein, 35 H2AX histone protein, 31, 36, 50 twin studies, 88 HRAS1 gene, 113 to virally associated neoplasia, 79 Hamsters HSP70 proteins, 52-53 X-linked disorders, 79 Chinese hamster ovary (CHO) cells, 48, 55, HSP90 proteins, 52 58, 59, 61 Genomic instability, radiation-induced, 11, 43 HTLV-1, 244 alpha particles and, 70, 71 DNA repair rates in Chinese hamster V79 Human cell lines/systems apoptosis and, 48-49 cells, 52 chromosomal instability in diploid malignant transformation in embryo cells, 59, in bone marrow cells, 72 fibroblasts, 72 bystander effects, 54, 55, 70 61 fibroblasts, 51, 54, 55, 57, 58, 72 and cancer risk assessment, 251 mutation studies, 59 Hela hybrid system, 52, 59, 62 Hanford Site, 135, 190, 191, 192, 193, 197, 199, cell cycle effects, 49, 113 human-hamster hybrid, 51, 72 in CHO cells, 58 200, 213, 215, 230, 234, 235, 276 hypersensitivity to killing, 56 chromatid instability, 70-73 HAP1, 32 immortalized, 52, 58 Hardy-Weinberg equilibrium, 102 chromosomal aberrations and, 46, 47-48, 54, keratinocytes, 54-55 58, 59, 60-61, 70, 251 Health end point data, 76-77, 142 malignant transformation, 59, 62 defined, 47 Heart disease. See Cardiovascular disease MCF-7:W58 breast cancer, 56 Heat shock-related proteins, 52-53 delayed, in somatic cells, 127 mutagenesis in lymphoblastoid cells, 51, 59- DNA repair defects and, 48, 49, 72 Heavy metal exposures, 128, 242 60 dose-response relationship, 45, 46, 48, 49, Helicobacter pylori infection, 241-242, 302 myeloid tumor, 56 Hemangiosarcomas, 150 60-61 oocyte radiosensitivity, 99 frequencies, 47-48, 61 Hematopoietic cells, chromatid instability in, 70- TK6 lymphoblasts, 58, 59-60, 61 gene mutations and, 61, 66, 68, 70, 87, 88, 71 Human studies. See also Epidemiological studies Hemochromatosis, 93 113, 126-127 bone cancer, 84 guardian-of-the-genome hypothesis, 48-49 Hepatitis, 150, 153, 242, 302 genomic instability, 71 in hematopoietic cells, 70-71 Hepatoblastoma, 150 mutations at minisatellite loci, 113, 114, 128- Hepatocellular carcinomas, 150, 242 hypersensitivity to radiation and, 57, 71 130 manifestations, 47, 54, 55, 57, 58, 70 Heritable genetic effects in humans. See Genetic Hungarian congenital disease population, 95 at minisatellite and ESTR loci, 113, 126-127 diseases; Genetic effects of radiation; Huntington’s disease, 98, 125 Genetic risk assessment; Genetic modeling, 251 Hydrogen peroxide, 29, 30, 31, 40, 41, 42, 50, 53 in mouse mammary epithelial cells, 71-73 susceptibility to cancer 8-Hydroxyguanine, 31 in mouse melanocytes, 58 High-LET radiation. See also Alpha particles; Hydroxyl radical Neutrons persistent, 46 bystander effect and, 54 reactive oxygen species and, 48 bystander effects, 53-54 damage mechanisms, 29-30 RBE, 71 carcinogenesis, 49 production during energy transfer processes, chromosome aberrations, 45 target and lesions resulting in, 48 31 telomere-associated, 48, 71-73, 251 damage mechanisms, 2, 19, 36, 45 Hyperparathyroidism, 151, 153

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396 INDEX Hypersensitivity to radiation at low doses, 11, International Classification of Diseases, 95 L 32, 45, 47, 51, 55-57, 71, 82, 239 International Commission on Radiation Units Hypertension, 93, 95, 111, 153 and Measurements, 22, 375 Laboratory animals. See Animal studies; specific Hyperthyroidism, 165-166, 169, 182, 185, 226, International Commission on Radiological animals 234 Protection, 22, 81, 85, 103, 105, 109, Late Effects Study Group, 161, 162 Hypothyroidism, 226 124, 165, 197, 246, 274, 282, 283, 292- Latent health effects Hypoxanthine-guanine phosphoribosyl 293, 294, 297, 375 RBE of neutron doses and, 27 transferase (HGPT) mutation, 44-45 Intestinal carcinoma, 69, 70, 87, 88, 166 Lead, 200 Iodine deficiency, 244 LET. See Linear energy transfer Iodine-131 Leukemia I adaptive response to, 51 acute lymphatic, 144, 210, 218, 226 childhood exposure, 68, 169, 173, 215 acute myelogenous, 68-69, 144, 153, 164, IDDM2 gene, 113 diagnostic exposures, 171, 173, 234 227 Immune disorders, virally associated neoplasia, acute nonlymphocytic, 67, 162 dose-response relationship, 235, 276 79 environmental exposures, 68, 209, 214, 215, adult T-cell, 144, 244 Immune response, 66-67 233-235 age factors and, 144, 264, 288 Immunodeficiency, 34, 80 alpha particles and, 71 radiotherapy-related risks, 161, 165-166, 171, Immunoglobulin, 34, 66 182, 234 analysis of human data, 296, 307-308 Immunologic rearrangement, 35 and salivary gland tumors, 165 animal studies, 68-70, 71, 72, 73-74, 87 Immunophilins, 52 in ankylosing spondylitis cohort, 164, 165, thyroid cancer, 68, 161, 165, 171, 182, 214, In vitro assays. See also; Human cell lines/ 215-226, 233-235, 276 183, 289 systems; Lymphocytes; individual animal Iododeoxyuridine (125Idu), 48 in atomic bomb survivors, 68, 72, 142, 143, species 144, 153, 172, 244, 245, 269, 307-308 Ionizing radiation. See also Alpha particles; Beta adaptive response in mammalian cells, 51, particles; Exposure to ionizing radiation; BEIR V model, 246, 282, 283, 292 52, 62 Gamma rays; High-LET radiation; Low- breast cancer survivors, 159-160 bystander effect in, 53, 54-55 caretaker gene, 67 LET radiation; Natural background CHO cells, 48, 58, 61 radiation; Neutrons; X-rays in cervical cancer survivors, 157, 158, 183, chromatid instability in bone marrow cells, 71 background, 30-31 289 chromosome aberrations in human cells, 24, chemotherapy-related, 86, 160, 244 chemical aspects, 29-32 53, 58, 61, 72 damage mechanisms, 6, 26-27, 29-30, 40-42, Chernobyl accident and, 203-204, 216-222, defined, 375 239 225-227 extrapolation to in vivo transformation children, 84, 161, 168, 172, 209, 210, 211, defined, 1, 375 systems, 52, 57 detection, 2 212, 214, 216-222, 226-227, 233, 244 genomic instability, 58 direct effects, 19, 29-30, 31 chromosome aberrations and, 65, 68-69, 72, 74 of LET-related risks, 24 chronic lymphocytic, 157, 159-160, 162, 212, discovery, 1-2 M5S mouse embryonic skin cells, 52 indirect effects, 19, 29-30 244, 283, 307 malignant transformation, 51-52, 61-62 late effects, 11 chronic myelogenous, 144, 171 priming dose, 52 coherence of BEIR VII estimates with other low doses defined, 2 RBE, 24 photon spectral distributions, 20-22 studies, 288, 289, 294 somatic mutagenesis, 69 physical aspects, 19-29 deaths, 144 trypsinization and replating, 52, 62 diagnostic irradiation and, 170, 171, 172 sources, 3-6, 11 Inelastic scattering, 20 track structure, 21, 26-27, 29, 55, 62 dose fractionation and, 73 Infertility, hormonal, 164 types, xi, 2, 19-20; see also Gamma rays; X dose-response relationship, 71, 72, 73-74, 76, Institut Gustave Roussy, 160, 161, 169 77, 142, 144, 157, 158, 160, 161, 163- rays Institute for Energy and Environmental U.S. population exposure, 3-4 164, 165, 183, 184, 245, 264, 295 Research, issues raised by, 330-331 Iron-59, 200 environmental exposures and, 209, 210, 211, Institute of Haematology and Blood 212, 214, 216-222, 226-227, 228-229, I-SceI endonuclease, 48 Transfusology (Belarus), 203 Ischemic heart disease, 95, 153 233, 244 Internally deposited radionuclides. See also Israel Tinea Capitis Study, 68, 155, 156, 166- EPA model, 282 Iodine-131; other specific radionuclides etiology, 243 167, 181, 182, 183, 273, 292 alpha particles, 199-200 excess relative risk, 12, 295, 307-309 cancer risk estimates, 200, 276 frequencies, 77 Chernobyl accident and, 276 J genetic susceptibility, 80, 86, 87 dose estimates, 3, 4 human data, 72 dose-response relationships, 43, 276 Japanese nuclear workers, 198 ICRP model, 282 and lung cancer, 200 Jaslovske power plant, 197 in infants, 218-221, 226 measurement problems, 199-200 Juvenile osteocondrosis, 95 in utero exposures and, 172 naturally occurring, 30, 43 incidence, 244, 284 nuclear industry worker exposure, 190, 199- initiation mechanisms, 66-67, 68, 74 200 K internally deposited radionuclides and, 200 and prostate cancer, 200 latent, 68, 72 International Agency for Research on Cancer, Kerma doses, 144, 375 Kidney carcinoma, 66, 149, 161, 164, 166, 227, lymphocytic (nonacute), 67, 164 336 medical-exposure-related risks, 12, 289-290 International Cervical Cancer Survivor Study, 181 228, 269, 282, 293, 294 Ku-70, 35, 42, 56 misclassification of cause of death, 153 International Childhood Cancer Survivor Study, models, 144, 246, 264, 273-274, 307-308 Ku-80, 35, 42, 56 181 monocytic, 171

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INDEX 397 mortality, 189, 196, 197 Linear relative risk model, 137 RBE variation with dose rate, 21, 24 myeloid, 71, 72, 73-74, 76 applications, 138 sources, 1, 4 neutron RBE and, 29, 143 equation, 138 track structure, 21, 43-44, 55 NIH model, 295, 308 statistical inferences, 138-139 Lung cancer. See also Respiratory system cancer in nuclear industry workers, 14, 190, 191, Linear-quadratic model, 6 additive risk model, 150, 159, 242, 276 196, 197, 198, 199, 200, 201, 202-204, DDREF estimates, 246 adenocarcinomas, 50, 76 275, 288 defined, 375 age and, 147 nuclear weapons testing and, 214 dose-response relationship, 7, 24, 43-44, 47, age at exposure and, 150, 160 quantitative studies, 73-74 74, 201, 247-248, 250, 255, 257, 274, 280 alpha particle exposure and, 242 in radiologists and radiologic technologists, for leukemia, 14, 246, 292, 295 animal studies, 28, 50, 74, 76, 87 189, 204, 205 RBE derivation, 24, 28 in ankylosing spondylitis cohort, 164, 174 radiosensitivity of bone marrow, 173 Lineoleic acid 13-hydroperoxide, 40 in atomic bomb survivors, 68, 147, 148, 150, in radiotherapy recipients, 84, 157, 158, 160- Lipid peroxidation, 30, 34 242, 262, 269, 276 161, 162, 163-164, 165, 166, 168, 183- Liver cancer baseline lifetime risk estimates, 278 185 age at exposure and, 150 in benign breast disease cohort, 174 registry data, 142 alpha particles and, 68 in breast cancer survivors, 160, 174, 175 risk assessment, 143, 144, 245, 246, 273-274, atomic bomb survivors, 147, 148, 149, 150, in cervical cancer survivors, 157 285, 295, 296, 307-308 269, 298 chemotherapy and, 159 risk estimates, 173, 183-185, 277, 278, 280- baseline lifetime risk estimates, 278 childhood exposures and, 168, 175 282, 284, 289-290, 294, 307-308 death certificate data, 150 diagnostic irradiation and, 170, 174, 176 risk factors, 244 diagnostic irradiation and, 68 dose fractionation and, 176 sex differences, 73, 144, 284 dose-response relationship, 150, 201 dose-response relationship, 74, 76, 158, 160, in tinea capitis cohort, 166, 183 etiology, 242 163, 201, 255, 262 temporal distribution, 144 excess relative risk, 148, 301, 302 dosimetry, 159, 160 uncertainties in risk, 284, 285 hepatitis antigen status and, 150, 242 etiology, 242-243 UNSCEAR model, 282, 294 human studies, 68 excess relative risk, 12, 148, 150, 159 X-rays and, 71 incidence, 298, 303, 305 fluoroscopy and, 174, 175, 176, 288, 289 lex gene, 36, 37 metastatic, 150 genetic susceptibility, 86-87 Life expectancy, 153-154, 161 mortality, 298, 304, 306 in Hodgkin’s disease cohort, 158, 159, 174, Life shortening studies multiplicative model, 242 176, 242-243 in atomic bomb survivors, 153-154 risk factors, 241, 242 incidence, 174, 175, 242, 262, 278, 279, 284, and DDREF, 246 risk models and estimates, 242, 272, 278, 298, 303, 305 dose-response relationship, 76-77, 89, 153, 279, 280, 282, 284, 285, 294, 301, 303- internally deposited radionuclides and, 200 249, 255, 257, 258 306 latent, 159 as proxy for mortality, 28-29 Thorotrast exposure and, 150 medical-exposure-related risks, 174-176, 288 wasted radiation concept, 77 Liver disease and cirrhosis, 153, 242 mortality, 174, 175, 242, 278, 280, 282, 298, Life span, and paternal effect for mutations, 97 Los Alamos National Laboratory, 192, 197 304, 306 Life Span Study, 9, 12-13, 26, 141-154, 246-250, Low doses multiplicative effects, 158, 159, 176, 242 267-268, 285-308, 375. See also Atomic breast cancer risk, 86 in nuclear industry workers, 135, 190, 198 bomb survivors cumulative effects, 53, 155 in peptic ulcer cohort, 163, 174, 175, 288 Li-Fraumeni syndrome, 79, 80, 81, 82, 83, 84 defined, 2, 11 in radiologists and radiologic technologists, Linde facility, 190 DNA damage, 31 204, 205 Linear energy transfer (LET). See also High- dose-response relationships, 10, 43-45, 57- in radiotherapy-related risks, 157, 158-159, LET radiation; Low-LET radiation; 62, 73 160, 162, 163, 164, 166, 168, 174, 242, Restricted LET hyper-radiation sensitivity at, 55-57 288 and carcinogenesis, 24-26, 49 neutron RBE at, 28-29 repair kinetics, 76 and chromosome aberrations, 45 potential for beneficial effects, 10 risk models and assessment, 147, 148, 173, consistency with other studies, 57 probability of cell damage, 9-10 174-176, 242, 244-245, 272, 275, 278, defined, 19, 375 protracted exposure, 31 279, 280, 282, 284, 288, 294, 303-306 and DNA damage, 20, 26-27, 31, 245 solid tumors, 74 sex differences, 150, 176, 284 dose average, 19 n.1, 22, 23 Low-LET radiation. See also Gamma rays; in skin hemangioma cohorts, 174, 175, 176 and dose-response relationship, 9, 24, 43 X-rays smoking and, 87, 135, 138, 150, 158, 159, in vitro studies, 24 annual worldwide exposure from natural 174, 176, 198, 242, 276 microdosimetric analogue, 22, 23 sources, 2, 3, 4 uncertainties in risk assessments, 138 protons and electrons in water, 20 bystander effects for, 54-55 in uranium/underground miners, 138, 242 as quality-of-radiation measure, 22-24 carcinogenic effects, 245 Lymphocytes, 24, 34 radioepidemiologic studies, 24-26 cell lethality, 55-57 adaptive response in, 51, 53 RBE variation with, 21 damage mechanisms, 26-27 bystander effect, 53 track average, 19 n.1 defined, 375 chromosome aberrations, 45, 46, 51, 53, 57, Linear no-threshold (LNT) model, 9-10 dose units, xi 58, 59, 61, 86 basic assumption, 7 dose-response relationships, 45, 126, 158, dose-response relationship at low doses, 57, DDREF adjustment, 7 245 58, 60 defined, 375 epidemiological studies, 199 genomic instability, 49, 59 description, 6-8 in vitro studies, 22, 24 HPRT mutations, 60 dose-response relationship, 246 mutation rates, 9 immortalized, 57, 58 lifetime-risk example, 7-8 physics and dosimetry, 19, 21, 199 PHA-stimulated, 59, 61

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398 INDEX Lymphohematopoietic tumors, 67, 71 and breast cancer, 12, 26, 84, 86, 157, 160, biophysical, 45, 139, 246 Lymphoma 163, 176-180, 287 breast cancer, 148, 273 animal studies, 68, 73, 74, 76, 78 cancer risk estimates, 12, 26, 173-187, 240, bystander effects, 251 in atomic bomb survivors, 151, 153 241, 276, 286-290 data quality and completeness, 265 cell killing and, 74, 78 and circulatory diseases, 12, 185-187 defined, 375 in cervical cancer survivors, 157 coherence of BEIR VII model with other dose measurement and, 139, 266 Chernobyl accident and, 217, 227 studies, 286-290 dose-response relationship, 45, 73-75, 89, children, 209, 210 doses from, 30, 156 139, 245, 246, 249, 255, 256, 264-266 chromosome aberrations and, 65 epidemiological studies of exposure, 155-156 empirically based, 263-264 diagnostic irradiation and, 171 exposure limits, 43 evolutionary population genetic, 105, 106 dose-response relationship, 73, 74, 77, 78, 151 and leukemia, 12, 183-185, 289-290 excess absolute risk, 143, 285-286 environmental exposures and, 209, 217, 228- and lung cancer, 12, 174-176, 242 excess relative risk, 132, 143, 285-286 229 noncancer disease risk, 8, 12, 159, 160, 163, extrapolation from high dose to low dose, 9, etiology, 78 185-187 29 frequencies, 77 occupational exposures, 204-205 extrapolation from one population to another, genetic susceptibility, 80, 87 physician population as surrogate for dose, 329 88, 240-245, 253-254, 266 iodine-131 exposures, 171 and RBE, 276 finite-locus threshold, 105-108, 124 misclassification of cause of death, 153 risk modeling, 138, 146-147, 276 general mutagen model, 262 murine, 68-70, 73, 74, 78, 87 sources of, 4-5, 30 genetic susceptibility to cancer, 81-82, 85, initiation mechanisms, 66-67, 68, 69, 70, 73, and stomach cancer, 185 86, 88, 120-122, 251 74 and thyroid cancer, 180-182, 287 genomic instability, 251 and intestinal neoplasia, 88 Medulloblastoma, 69, 70, 80 heritable effects of radiation, 92, 120-122, mortality, 151 Melanoma, 67, 80, 151, 161, 162, 190 251 pathogenesis, 74 Menadione, 40 Interactive RadioEpidemiological Program, in radiologists and radiologic technologists, Mendelian diseases, 92-93, 94-95 295 204, 205 Meningiomas, 80, 166-167, 168 leukemia risk, 144, 246, 273-274 radiotherapy and, 164 Mental retardation, 1 linear no-threshold, 6-10, 375 sex differences, 74, 151 Mercury, 200 linear relative risk, 137, 138-139 target cells, 74 Metropathia hemorrhagica, 164 linear-quadratic, 6, 43, 246 thymic, 12, 68, 73, 74, 76, 78 Michael Reese Hospital, 169, 181, 182 mathematical, 92, 261-262 Microarray expression studies, 39, 53 medical-use-related risks, 138, 146-147 Microdeletion syndromes, 112 Moolgavkar-Knudson two-stage clonal M Microdosimetry, 22, 23 expansion model, 241, 253-254, 262 Microencephaly, 80 multifactorial threshold model of disease Macrophage oxidative bursts, 29 Micronuclei, 47, 51, 54, 55 liability, 93, 105, 107, 120-121, 252 Mallinckrodt facility, 200 Minisatellite loci, 113-114, 128-130 multiplicative, 148, 163, 240, 241, 242, 243, Malondialdehyde, 34 Mitochondrial electron transport, 49 254, 297 Mammary cancer. See also Breast cancer, female Mitogen-activated protein kinase (MAPK), 55 multivariate, 138, 265 adenocarcinomas, 50, 74 MLH1 gene, 67, 80 NCRP review of, 293 bystander effects, 55 MLH2 gene, 80 parameter estimation, 264, 285-286 chromatid instability and, 71-73 Model fitting parametric, 143, 296, 299 hormones and, 28 AMFIT program, 143, 269, 296 polygenic computational, 86 in mice, 69, 71-73 EPICURE software, 138, 143, 269, 296 population, 85, 88, 286 neutrons and, 28, 50 to epidemiological data, 138, 269 postirradiation cancer mechanisms and in rats, 28 leukemia data, 144 choice of, 241 Mammography, 4, 20, 21, 22, 24 maximum likelihood estimates, 138, 139, 296 preferred (BEIR VII) model, 6-8, 138, 244, Man-made radiation preferred risk models, 296-308 264, 269-278, 310-312 sources, 3-4 for site-specific cancers, 303-307 probability, 260, 265 U.S. population exposure, 3-4 for solid cancers, 298-302 projections of cancer risk over time, 239-240 MAPK, 39 summing solid cancers, 279-280, 296 relative risk, 25, 26, 137, 138-139, 148, 149, Marfan syndrome, 92, 98 Wald method, 138 159, 164, 175, 240, 242, 243, 244, 253 Massachusetts General Hospital, 165 Models/modeling. See also Cancer risk solid cancers (all), 143, 269-271 Mastitis patients, radiotherapy-related cancer, 26, assessment; Genetic risk assessment; threshold, 12, 74-75, 105-108, 120-121, 124 163, 177, 180, 243, 287, 292, 293 Uncertainties thyroid cancer, 273 Mathematical models. See Models/modeling absolute risk, 242, 244, 245, 253-254 Moolgavkar-Knudson two-stage clonal Mayak plutonium production complex, 57, 190, adaptive response, 250-251 expansion model, 241, 253-254, 262 201-202, 212, 213, 214, 215, 235, 275, 276 additive risk, 148, 150, 159, 240, 241, 242, Mortality Mayo Clinic, 165 244-245, 254 ankylosing spondylitis cohort, 164, 165 Maximum likelihood principle, 138, 139 age-at-exposure effects, 143, 264, 297-298 atomic bomb survivors, 130, 131, 141, 142, MCF-7:W58 cell lines, 56 applications of, 264-265 143, 144, 145, 147, 151, 152-153, 298- Medical uses of radiation. See also Diagnostic Armitage-Doll, 262 307 radiation; Radiotherapy studies atomic bomb survivor data, 143-144, 262, cancer, 2, 4-5, 28-29, 68, 76-77, 142, 144, adaptive response to, 51 263, 296-308 145, 151, 165, 170, 172, 174, 175, 176, age at exposure, 297 BEIR III, 138 177, 181, 189, 191, 194-198, 200, 201, atomic bomb survivor data combined with, BEIR V, 246 202, 203, 204, 205, 209-212, 242, 243, 146-147 biologically based, 147, 262-263 298-307

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INDEX 399 dose-response relationships, 145 telomere-deficient strains, 48 Mutation component of genetic diseases healthy worker effect, 136 Trp53-deficient, 78 application, 102 life shortening as proxy for, 28-29 tumorigenesis, 68-70, 71-75, 82-83 autosomal dominant diseases, 102, 103-105, lymphoma, 151 MRE11, 37 111, 115, 116, 119 nonneoplastic disease in atomic bomb Mre11/Rad50/Nbs1, 38 autosomal recessive diseases, 104, 105, 110- survivors scans, 141, 152-153 MSH2 gene, 67 111, 115 premature, 8 Mucoepidermoid carcinoma, 150 BEIR V estimates, 94, 106, 115 solid cancers, 144, 145 Multifactorial diseases, 8 chronic multifactorial disease, 105-113, 119 Mound Facility, 191, 192, 197 baseline frequencies, 95-96 concept, 94 Mouse/murine studies BEIR V estimates, 95, 96, 115, 117 congenital abnormalities, 105-106, 111, 116 adaptive response, 51, 52, 53, 55, 78 BEIR VII estimates, 96 defined, 94, 101-102, 111 AKR strain, 78 cancer as, 81 dose-response relationship, 108, 245 Apc-deficient genotype, 69, 70, 87 chronic, 95, 96, 105-113, 115, 117, 119, 124 for early postradiation generations, 106, 116 Atm-deficient, 82-83 congenital, 93, 95, 96, 112, 117 at equilibrium, 94, 106 BALB/c, 71, 74, 76, 127 defined, 93 estimation, 103-113 BRCA-deficient, 82-83 doubling dose, 94, 95-96, 101, 115 finite-locus threshold model, 105-107, 108, cataracts, 115 estimates of risk, 115, 117 111, 124 C3H 10T1/2 cells, 50, 52, 55, 59, 61-62 examples, 93 first-generation increase in mutation rate and, C3H/HeN strain, 126 familial aggregation studies, 122 103, 104, 105, 106-108, 109, 119 C57BL/6 strain, 71, 127 genetic basis, 93, 95-96, 124 gene-gene interactions (epistasis) and, 108 CBA strains, 71, 73-74, 78, 127 models, 93, 95, 105-106, 120-122, 124 Hardy-Weinberg equilibrium, 102 chemotherapy studies, 130 multisystem developmental abnormalities, heritability of liability concept, 105, 106, chromatid instability, 71-73 112-113 107, 111, 121-122, 124 chromosome aberrations, 48, 57, 58, 119 mutation component, 81, 94, 101, 105-113, ICRP hybrid model, 105, 109 congenital abnormalities, 115, 116, 131 117, 119, 124 multisystem developmental abnormalities, DNA repair, 34, 42 potential recoverability correction factor, 119 112 dose-rate reduction factor, 100 n.1 prevalence, 95 murine studies of induced mutations, 109- dose-response relationships at low doses, 58, risk estimates, 117, 119 111, 112-113, 116, 124-125 60, 73-75, 76, 78, 126 threshold model, 93, 94, 120-121, 124 mutation-selection balance, 94, 102, 103, doubling dose, 96-97, 98-101, 113 Multifactorial threshold model of disease 105, 106, 107, 109, 117 ESTR mutations, 113, 114, 125-127 liability, 93, 105, 107, 120-121 nonsporadic cases, 103 extrapolation of data to humans, 73, 96-98, Multiple dystrophy, 98 numerical estimates, 104-105 114, 115 Multiple endocrine neoplasia, 80 permanent increase in mutation rate and, 104, gene deletions in melanocytes, 58, 61 Multiple exotoses, 98, 125 105, 106-109 genetic effects of radiation, 92, 98-101, 109- Multiple myeloma, 151, 164, 171, 204, 205, 214 “phenotypes” of human diseases, 111-113 111, 112-113, 115-116, 119 Multiplicative effects, 148, 150, 163, 240, 241, population genetic concepts, 102 genetic models of tumorigenesis, 58, 61, 68- 242, 243, 254, 297, 376 potential recoverability correction factor, 70, 82-83, 87 Mutagenesis 109-110, 111, 125 genome sequencing, 119, 125 adaptive response, 51 rationale for, 101-102 genomic instability as gene deletions, 58, 61 alpha particles, 53, 54, 68 spontaneous mutations in humans, 109-111, Harderian gland tumors, 74 apoptosis and, 49 124-125 HPRT mutations, 44-45, 58, 60 bystander effects, 54 sporadic, 103-104, 108 human counterparts of genes, 98, 99 cell cycle phase and 49, 50, 81, 113 strengths and weaknesses of, 119 induced mutation rates, 92, 98-101 in cells hemizygous for autosomal APRT, 46 UNSCEAR, 109 intestinal tract cancers, 87 chromosome aberrations and, 47 X-linked diseases, 104, 105, 111, 115, 116, leukemia, 68-70, 72, 73-74 DDREF, 246 119 lung cancer, 28, 50, 74, 76, 87 DNA damage and repair processes and, 47, Mutation rates lymphoid neoplasms, 68-70, 73-74, 78 65, 246 age and, 97 malignant transformation, 59, 61-62 dose fractionation and, 57 animal studies extrapolated to humans, 96-98 mammary tumors, 50, 71-73, 74, 88 dose-rate effects, 50 in atomic bomb survivors, 6, 114, 129, 130- minisatellites, 125-126 dose-response relationship, 47, 50, 57, 59-60, 131 ms5S embryonic skin cells, 51, 52 61, 113 calculating rates in mice, 99-100, 119 multisystem developmental abnormalities, at ESTR loci in mice, 113-114 in children of atomic bomb survivors, 114 112-113 genetic context, 46 in children of Chernobyl inhabitants/cleanup mutation studies, 8, 44-45, 47, 50, 56-57, 58, germline, 47, 65, 114 workers, 114, 128, 129-130 60, 92, 98-101, 109-111, 112-113, 126- at HPRT gene, 47, 51, 53, 58, 59-60, 61 dominant disorders, 98, 100 127, 130 hypersensitivity to radiation and, 56-57 dose fractionation and, 99 oocyte killing, 24, 75, 98-99, 130 mechanisms, 27, 46-47, 126 in early postradiation generations, 106 ovarian tumors, 50, 74, 75, 76 at minisatellite loci in humans, 113-114 effects at equilibrium following permanent quantitative studies, 73-75 radiation quality and, 47 increase, 106-109 radiosensitivity, 42, 56-57 RBE variation with LET, 24, 47 at ESTRs, 126-127 RFM strain, 28, 29, 73-74, 75 in somatic cells, 46-47, 113, 246 family size and, 97 skeletal abnormalities, 115 in spermatogonia, 60 in first generation, 105, 106, 108, 129 skin cancer, 75, 87 target genes, 47 and fitness of a population, 102 solid tumors, 74-75 in TK6 human lymphoblastoid cells, 59-60, and genetic disease risk in humans, 109-111 spermatogonia mutations, 50, 98 61 in human genes, 97-98

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400 INDEX mice, 92, 96-101, 109-111, 114, 126 Myelodysplastic syndrome, 153 fission-spectrum, 20, 28, 50 at minisatellite loci, 114, 128-130 MYH gene, 67 high-energy, 19 parental birth year and, 129 Myocardial infarction, 153 leukemia, 71 in progeny, 70, 97 Myotonic dystrophy, 92 linear dose coefficient, 28 sex differences, 96-97, 119, 128 and lymphoma, 68 spermatogonial stage, 100, 113 mutations in mice, 68, 126, 127 spontaneous, 97-101 N occupational exposures, 199, 204 X-linked diseases, 98 physics, 19 Mutations. See also Chromosome aberrations; Nagasaki Tumor Registry, 268 RBE, 20, 27-29, 126, 142, 143, 146, 297 DNA damage; Genetic effects of National Council on Radiation Protection and weighting factor for absorbed dose, 296-297 Measurements, 43, 293, 376 radiation; Spontaneous mutations Nevoid basal cell carcinoma syndrome, 80, 82, animal tumors, 68-70, 96-98 National Institutes of Health 83, 84 in atomic bomb survivors, 6 cancer risk model, 138, 268, 269, 273, 277- New York State Postpartum Mastitis Study, 26 278, 293 autosomal dominant, 98 NF1 gene, 66, 80, 81 basic concepts, 327-328 radioepidemiological tables, 294-296, 299 NF2 gene, 80 biochemical (null enzyme), 98, 99, 131 National Radiological Protection Board, 82, 85, NF-kappaB transcription factor, 51, 53 293 broad-sense and narrow-sense heritability Nijmegen breakage syndrome (NBS), 79, 80, 81, and, 121-122 National Registry of Radiation Workers (UK), 83 and cell death, 47 14, 190, 193, 195, 196, 197, 198, 200, 4-Nitroquinoline-N-oxide (4NQO), 75, 76 230, 290 Chernobyl accident and, 128-129 Non-Hodgkin’s lymphoma, 151, 157, 158, 162, complex, 51 National Research Council 164, 171, 209, 227, 229, 231 congenital abnormalities, 131 Committee on Atomic Casualties, 91 Nuclear Electric, 190 Committee on the Biological Effects of defined, 327 Nuclear facilities. See also Nuclear industry deletions, 36, 40, 47, 54, 65, 109 Atomic Radiation, 91 workers; individual facilities detection, 127, 129-130 Committee on the Biological Effects of accidents, 208, 209, 211, see Chernobyl Radiation, 91; see also BEIR entries dominant negative, 125 accidents dose-response relationship, 47, 57, 59-60, 73, Natural background radiation commercial power plants, 3, 190 113, 114, 246 annual effective dose per person worldwide, dosimetry in population exposures, 209-211, 2, 3, 4, 30, 43 in Drosophila melanogaster, 8 212, 213, 214, 229-232 electrophoretic, 131 cancer risk, 7-8, 228 fuel processing plants, 190, 199-200, 209, first generation, 130-131 chemical aspects, 30-31 212, 213, 215, 229, 234 defined, 373 frequencies, 46-47, 94, 105 and leukemia, 190, 213 gain-of-function, 66, 81, 125 DNA damage, 30-31 occupational exposures, 190 germline, 6, 8, 81, 103, 109; see also Genetic dosimetry, 228 population exposures in proximity to, 208- ecologic studies, 228 susceptibility to cancer 215 high-penetrance, 81, 85 in Great Britain, 228 U.S. population exposure to radiation from, HPRT, 44-45, 47, 53, 58, 60 high-dose exposures, 4 3, 5 in Kerala, India, 228 human minisatellite loci, 128-129 Nuclear Industry Family Study, 233 human tumors, 66-67 low-dose exposures, 4, 8, 31, 43 Nuclear industry workers. See also Occupational indirect, 127 occupational exposures, 204 radiation exposure; individual facilities sources, 2, 3, 30, 43 intragenic, 109 and sites lethal, 47 uncertainty in estimates, 3, 7 age associations, 200 loss-of-function, 66, 67, 81, 125 U.S. population exposure, 3 assessment of exposure, 193-194 in Yangjiang County, Guangdong Province, low-penetrance, 85-88 atomic bomb survivors compared, 201, 203 at minisatellite loci in humans, 113, 114, China, 228 bone cancer, 201 128-129 NBS gene, 80 cancer incidence and mortality estimates, Nbs1, 36 missense or nonsense, 125 191, 194-198, 200, 201, 202, 203 mouse studies, 8, 44-45, 47, 50, 56-57, 58, NBS1, 37 cesium-127 exposure, 202 60, 92, 98-101, 109-111, 112-113, 125- Nephroblastoma, 66, 80 Chernobyl liquidators, 57, 58, 60, 114, 129, Nervous system 126 202-204, 226, 227 multilocus, 46 benign tumors, 152 childhood cancers following parental multisite DNA fingerprinting, 129 cancer of, 148, 149, 151, 152, 171 preconception exposures, 229, 230-232, Neural tube defects, 93 point, 46, 66, 125, 131 233 potentially recoverable, 109-111, 112 Neurofibromas, 66, 80 chromosome aberrations, 57, 58 radiation-induced tumors, 67-68, 239 Neurofibromatosis, 80, 84, 92, 98 cohort characteristics, 191-193 Neutrons recoverability of genes in live births, 109- commercial nuclear power facilities, 190 111, 124, 125 animal studies, 28-29, 68, 126 confounding factors, 136, 198, 199-200 relative risk, 6 atomic bomb survivors, 20, 27, 142, 143, 146 defined, 190, 191 carcinogenesis, 50 reversion, 47 design of studies, 138-139, 198 single-gene, 46 cell cycle effects, 50 dosimetry, 60, 138-139, 190, 191, 192, 193, somatic, 103, 113 cell killing, 28 198-199, 201, 202, 203, 231, 233, 290 chromosome aberrations from, 27-28 specific-locus, 60, 100 epidemiological studies, 138-139, 189, 190- spontaneously arising tumors, 66-67, 239 damage mechanisms in tissues, 19, 27 193, 233 trinucleotide repeat expansions, 125 dose-effect relationship, 28 follow-up studies, 190, 192, 193, 202-203 DS02 dosimetry, 27 Tradescantia, 24 Hanford workers, 135, 190, 191, 192, 195, and tumor susceptibility, 66-67, 242 DS86 dosimetry, 27, 142 196, 198-199

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INDEX 401 healthy worker effect, 194 Occupational radiation exposure. See also Pantex, 190 heavy metal exposures, 200 Nuclear industry workers; Radiation Paracrine growth factors, 86 internally deposited radionuclides, 190, 193, workers; specific occupations and Paracrine proapoptotic or antiapoptotic factors, 194, 199-200, 201 cohorts 54 leukemia, 14, 190, 191, 196, 197, 198, 199, adaptive response, 51, 53 Parathyroid cancer, 80 200, 201, 202-204 airline and aerospace employers, 204 Parkinson’s disease, 153 liver cancer, 201 BEIR V report, 190 Parotid gland, tumors of, 171 lung cancer, 135, 190, 198, 200, 201 and cardiovascular disease, 199 PCNA (proliferating cell nuclear antigen) at Mayak plutonium production complex, 13- confounding in, 136, 189, 194, 198, 199-200, protein, 32, 33, 39, 53 14, 57, 190, 201-202 205 Peptic ulcer, 163, 174, 175, 185, 242, 287, 288 modifiers of radiation risk, 200-201 dose limits, 5, 43 Peroxyl radicals, 31 monitoring exposure, 189, 201 dose-response relationship, 189 Phenylketonuria, 93 multiple myeloma, 197 epidemiological studies, 189-190 Phosphatidyl-3-inosityl enzymes, 36 mutations, 60 healthy worker effect, 189, 194, 205 Phosphorylation plutonium exposure, 190, 194, 199, 200, 201- medical and dental personnel, 189, 204-205, of histone protein, 36 202 266; see also Radiologists and radiologicl of kinases, 37 pooled analyses of studies, 14, 191-193, 194- technicians Photo effect, 22 195, 198, 200 monitoring, 189 Photoelectric process, 20 prostate cancer, 197-198, 200 Portsmouth Shipyard Study, 135, 136 Photons protracted exposures, 200-202 and reproductive health, 5, 233 absorption and scattering, 20-21 reproductive health, 233 risk estimates, 280 annihilation events, 21 risk estimates, 194-198, 203-204, 290 sensitivity of studies, 5-6, 189 defined, 376 risk modeling, 138, 262, 268, 275, 290 skin cancer, 2 energy transfer, 19, 20-21 Sellafield Nuclear Facility, 57, 58, 190, 192, types of, 189 linear dose coefficient, 28 194, 195, 196, 197, 229, 230, 231 uncertainty in, 14 penetration depth, 21 sensitivity of studies, 5-6 of U.S. population, 3, 5 spectral distributions, 20-22 skin cancer, 190 Ocular albinism, 93 Photosensitivity, 80 smokers/smoking, 194, 198, 199 Oncogenes. See also Proto-oncogenes; Physical aspects of ionizing radiation socioeconomic status, 199 Tumorigenesis, radiation induced epidemiological studies, 24-26 solid cancers, 201 activation, 65 experimental observations, 28-29 thyroid cancer, 203-204 defined, 376 genetic damage mechanisms, 26-27 uncertainties in data, 14, 194, 198 Oncovin, 130 in vivo studies, 24 Nuclear medicine, U.S. population exposure Oocytes LET, 22-24 from, 3, 5 chemotherapy effects, 130 neutron interaction with tissue elements, Nuclear membrane damage, 29, 49 primordial, 92 27-29 Nuclear Regulatory Commission (U.S.), 2 sensitivity to cell killing, 75, 98-99, 119 photon spectral distributions, 20-22 93 Oropharyngeal cancers, 148, 149 RBE, 22-29 Nuclear weapons testing Osteogenesis imperfecta, 98, 103, 125 track structure, 10, 21 Bikini test site, 234 Osteopetrosis, 98 types of radiation, 19-20 British tests, 212, 213, 214, 235 Osteosarcoma, 69, 78, 87. See also Bone cancer PI-3 kinase, 67 Castle BRAVO, 214 Otosclerosis, 98 Pituitary tumors, 74, 152 dosimetry, 212, 213, 214 Ovarian carcinoma Plutonium-239, 20, 190, 194, 199, 200, 201 and leukemia, 212, 213 in atomic bomb survivors, 147, 148, 149, 269 PMS1 and PMS2 genes, 60 multiple myeloma, 214 dose-response relationship, 12, 50 Poly-ADP-ribose synthetase, 32, 33, 34 mutation rates, 114, 128-129 genetic susceptibility, 67, 69, 74, 75, 76 Polycystic kidney disease, 98 Nevada Test Site, 234 incidence, 298 Polymerase β (POL β), 32, 33, 34, 35 Operation HARDTACK, 213 mortality, 298 Polymerase δ (POL δ), 32 Operation UPSHOT-KNOTHOLE, 6 radiotherapy-related, 80, 84, 160, 164 Polymerase chain reaction, 127, 130 participant exposures, 6, 212, 213, 214 risk models and estimates, 272, 278, 279, Polynucleotide kinase (PNK), 32, 33 population exposures, 3, 5, 6, 114, 212-215, 280, 282, 285, 294, 303-306 Polyposis of intestine, 98 234, 276 Oxford Survey of Childhood Cancer, 10, 172-173 Porphyria, 98 Semipalatinsk test site, 114, 128-129 Oxidative stress Portsmouth Naval Shipyard Study, 135, 136, and thyroid cancer, 212, 215, 234, 276 adaptive response to, 50 191, 192, 197, 200 U.S. tests, 6, 213, 234 DNA damage, 19, 30-32, 34, 40-42, 50 Postradiation generation progeny Nucleotide pools, alterations in, 48 DNA repair, 31-32, 40-42, 48 first, 116 Oxygen, and radiation resistance, 50 genetic disease risk, 116 oxyR transcription factor, 50 mutations in, 70 O second, 116 Potential recoverability correction factor Oak Ridge National Laboratory, 190, 191, 192, P (PRCF), 119 193, 194, 195, 196, 198, 200 for autosomal dominant diseases, 110, 115, 119 Oak Ridge X-10 Plant, 191, 192, 195 p21 protein, 37, 39, 53, 54 for autosomal recessive diseases, 110-111, 115 Oak Ridge Y-12 plant, 190, 191, 192, 195, p53, 35, 36, 37, 39, 48, 49, 53, 54 BEIR V methods compared, 115 200 Pair-production process, 20-21 for chronic multifactorial diseases, 111, 115, Observational studies, defined, 133 Pancreatic cancer, 147, 148, 149, 163, 164, 168, 119 204 for congenital abnormalities, 111

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402 INDEX estimates, 110 Radiation protection benign breast disease cohorts, 163, 174, 177, multisystem developmental abnormalities, control measures, 193, 276 180, 185 115 dose units, xi for benign diseases in adults, 155, 162-166 and revision of risk estimates, 109-110 genetic susceptibility implications for, 85 benign diseases in children, 155, 166-167, strengths and weaknesses, 111, 119 photon energy considerations, 24 181 weighted, 115 protracted exposures and, 189 benign gynecological diseases, 163-164 for X-linked diseases, 110, 115, 119 quality factor, 22 bladder cancer in recipients, 157, 158, 162, pRb, 39 RBE and, 276 163, 164 Prednizone, 130 Radiation quality. See also Quality factor bone cancer in recipients, 157, 161, 162, 164, Pregnancy outcomes, adverse, 8, 131 LET as a measure of, 22-24 167 Primary basilar impression, 98 and mutation frequency, 47 brachytherapy recipients, 162 Premature chromosome condensation techniques, weighting factor, xi, 24 breast cancer patients, 26, 84, 86, 135, 157, 46 Radiation resistance, 30, 32, 40-42 159-160, 164-165, 167, 168, 169, 174, Prkdc gene, 71 as adaptive response, 37, 51 175, 176-180, 186-187, 205, 243 Procarbazine, 130 DNA repair, 49 cardiovascular disease mortality, 159, 160, Prolactin, 76 priming dose and, 51 185-187 Prostate cancer, 147, 148, 149, 164, 200, 204, 269, Radiation weighting factor, xi, 24 cell killing, 155 272, 278, 279, 280, 282, 298, 303-306 Radiation workers. See Nuclear industry cervical cancer survivors, 26, 135, 157-158, Prostate hyperplasia, 153 workers; Occupational radiation 174, 176, 177, 185 Protein kinases, 35-39, 51, 55 exposure children, 9, 84, 156, 161-162, 166-170 Protein-8 (XIP8), 56 Radical scavengers, 29, 30 chromosomal aberrations, 53 Protracted exposure Radioisotopes. See also specific radioisotopes dose-response relationship for secondary and bone cancer, 75 diagnostic exposures, 156 cancer, 157-170 and breast cancer, 176, 180, 243 natural in human body, 30, 43 dosimetry, 155, 156-157, 159, 161, 176-177, and cancer risk assessment, 241, 243 Radiologists and radiologic technicians 183, 184, 186, 187 and DNA damage, 31 breast cancer, 205 extrapolation to other populations, 155 dose-rate effects distinguished from, 77 colon cancer, 205 genetic effects, 9 genetic risk assessment, 92 leukemia, 189, 204, 205 Hodgkin’s disease patients, 130, 158-159, and life span, 76, 77 lung cancer, 204, 205 174, 176, 177, 242-243 occupational, 189, 200-202 lymphoma, 204, 205 for hormonal infertility, 164 radiation protection implications, 189 mortality rate, 2, 189, 204, 205 hyperthyroidism studies, 165-166, 169, 181, reduction in risk for, 246 multiple myeloma, 204, 205 185, 234 thyroid cancer, 182 pancreatic cancer, 204 for malignant diseases, 9, 130, 155, 156, 157- and tumorigenesis, 75 prostate cancer, 204 162 Protons skin cancer, 2, 204, 205 and minisatellite mutations, 114, 130 dose-effect relationships, 28 Radionuclides. See also Internally deposited mouse studies, 130 energy transfer, 19, 20 radionuclides; specific radionuclides non-Hodgkin’s lymphoma patients, 162 recoil, 27, 28 in utero exposures, 330 occupational exposures, 205 Proto-oncogenes, 66, 68, 80, 81-82 organically bound, 330 ovarian cancer patients, 160 PTC gene, 80 in work environment, 199-200 in peptic ulcer patients, 163, 174, 175, 185 Ptch gene, 66, 68, 69, 82, 83 Radiosensitivity postpartum mastitis cohorts, 26, 163, 177, 5´,8-Purine cyclodeoxynucleosides, 34 age and, 68 180 Pyloric stenosis, 120 animal studies, 34, 69, 71, 82-83 and radiosensitivity, 82, 83-87, 155 Pyrimidopurinone, 34 of bone marrow, 173 registries, 155 of breast tissue, 56, 86, 173 secondary tumors, 84-85, 86, 88, 135, 155, cardiovascular system, 185-186 157-162, 173-187 Q cell cycle phase and, 45, 49-50, 55, 82, 83, site-specific cancer risk estimates, 173-187 86, 113 and skin cancer, 68 Quality factor (Q) and cell killing/lethality, 55-57 skin hemangioma cohorts, 168-169, 174, basis for, 22 chromosomal, 82, 86 175, 176, 177, 180, 181, 183, 185 defined, 376 DNA repair defects and, 32, 34, 37, 40, 56, testicular cancer patients, 160-161 Quantitative studies 69, 71, 80, 82, 83, 87, 239 thymus gland enlargement, 156, 167-168, in experimental tumorigenesis, 73-79 dose fractionation, 55 176, 177, 180, 181, 182 gene polymorphisms, 87 thyroid cancer patients, 161 heritable, 82-85, 87 thyroid diseases (benign), 165-166, 169 R human data, 82, 83-85 tinea capitis cohort, 68, 155, 156, 166-167, RAD50, 37 hypersensitivity to low doses, 11, 32, 45, 47, 181, 182, 183 Rad51, 38, 53, 82, 83 51, 55-57, 71, 82, 239 tonsil enlargement cohort, 155, 169, 181 RAD52, 38 mutational, 47, 98-99 uterine cancer patients, 162 RAD54, 38 of oocytes, 75, 98-99, 119 Radium-224, 2, 269 Radiation Effects Research Foundation, 91, 140, sex differences, 119 Radium-226, 163, 164, 168, 169, 183, 185, 209 141, 142, 152, 267, 269, 270, 271, 285, thyroid gland, 173, 234 Radon, 30, 262. See also Uranium miners 286, 296, 297, 298, 301, 302, 307. See and tumorigenesis, 82-85, 87 and lung cancer, 242 also Atomic bomb survivors; Life Span Radiotherapy studies sources, 3, 43, 68 Study ankylosing spondylitis cohort, 164-165, 174, Randomized intervention trials, 133-134 176, 177, 185 Rare diseases (early onset), 98

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INDEX 403 RAS gene, 68 Respiratory system cancer. See also Lung cancer Sellafield Nuclear Facility workers, 57, 58, 190, Rats atomic bomb survivors, 149, 292 191, 192, 195, 196, 197, 198, 199, 200, Eker strain, 82, 83 Chernobyl accident and, 218 229, 230, 231, 233 mammary cancer, 28, 74, 76 model, 292 Seminoma, 130 renal carcinoma in Tsc-2-deficient genotype, Restricted LET Semipalatinsk nuclear test site, human 69 defined, 19 n.1 minisatellite loci mutations, 114, 128-129 skin cancer, 75, 76 dose averages, 22, 23, 24 Signal transduction pathways Sprague-Dawley strain, 28, 74 Retinal tumors, 80 adaptive response, 51, 53 tumor-suppressor-gene-deficient, 82, 83 Retinoblastoma, 80, 84, 98, 103, 125, 161 bystander effects, 53-54, 251 RB1 and RB2 genes, 80, 125 ret/PTC genes, 68, 81-82, 246 DNA repair, 32, 34, 36-39, 48, 49, 54, 80 Reactive oxygen species, 31-32, 40-42, 48 Rhesus monkeys, oocyte radiosensitivity, and dose-response relationships, 62 adaptive response to, 50 99 and genomic instability, 78 bystander effect, 54 Risk assessment. See also Cancer risk hypersensitivity to radiation and, 56 Rectal cancer assessment; Genetic risk assessment; Sister-chromatid in atomic bomb survivors, 147, 148, 149, Models/modeling exchanges, 36, 53, 54 151 absolute risk, 260-261 fusion, 48, 71 radiotherapy-related risks, 157, 158 BEIR I approach, 138 replication, 49, 245 Relative biological effectiveness (RBE) Committee approach, 6-9 Skeletal disorders, 80, 112, 115, 116. See also alpha particles, 71 confidence intervals, 133, 136, 137-139, Bone cancer animal studies, 28-29 176 Skin cancer and cancer risk assessment, 276 defined, 377 age dependency, 298 cell cycle phase and, 50 definition of risk, 260 animal studies, 74, 75, 76, 87 and chromosome aberrations, 24, 27-28, 276 direct estimates, 261, 290 in atomic bomb survivors, 148, 149, 150- defined, 376 excess risks, 132, 137-138, 260-261 151, 269, 295 dose-rate effects on, 21, 24, 28 incidence rates and, 259, 260-261 beta particles and, 75 experimental observations, 28-29 incomplete covariate information and, 265 caretaker gene, 67 gamma rays, 21, 22-24, 126, 276 lifetime risk projections, 137, 240, 264-265 children, 161, 167 and gene mutations, 47 mathematical models, 261-262 dose-response relationship, 74, 76, 151, 245 and genomic instability, 71 measures of risk, 132 excess relative risk, 148 LET of radiations and, 21, 24, 31, 47 methodology, 137-138, 259-261 fluoroscopy and, 2 neutrons, 20, 27-29, 126, 143, 146, 297 pooling data from multiple studies, 169, 172 gatekeeper gene, 66 protracted exposure and, 75, 176, 180, 243 probability models, 260, 265 genetic susceptibility to, 80, 84, 87 uncertainty in, 29, 286 RBE in, 28 latent damage, 76, 167 X-rays, 22-24, 276, 286 relative risk, 261 in mice, 69, 76 Relative risk, defined, 132, 376 risk models, 138-139, 261-266 in radiologists, 2 Renal carcinoma, 69, 70, 80, 222 sample sizes, 297 radiotherapy-related risks, 84, 162, 167 Research recommendations validity of estimates, 266 risk estimates, 245, 270-271, 282, 294, 295 adaptive response, 53, 314 Rochester Thymus Study, 26, 180, 181, 292 in tinea capitis radiotherapy patients, 68, 167 atomic bomb survivor studies, 18, 317-319 Rocketdyne/Atomics International, 191, 192, UV-induced, 75, 151 baseline frequencies of Mendelian diseases, 194, 197, 200 xeroderma pigmentosum and, 79 316-317 Rocky Flats, 190, 191, 192, 193, 195, 196, 197, Skin hemangioma cohort, 26, 168-169, 172, 174, biological phenomena at low doses, 9, 16-17, 199 175, 176, 177, 178, 180, 181, 183, 185, 314-315 Roentgen, Wilhelm Conrad, 1-2, 156 287 bystander effects, 314 RPA, 38 Smoke detectors, 3 Chernobyl cleanup workers, 204 Russell, William, 100 n.1 Smokers/smoking doubling dose calculations, 316 Ruthenium-106, 212, 213, 214 and carcinogenesis, 242 environmental radiation studies, 17-18, 321 confounding in radiation studies, 57, 138, epidemiological studies, 18, 317-321 150, 198, 199, 242, 245 genetic effects of radiation, 17, 316-317 S and liver cancer, 242 genetic susceptibility to cancer, 17, 315 and lung cancer, 87, 135, 138, 150, 174, 176, genomic instability, 49, 53, 315 Saccharomyces cerevisiae, DNA repair in, 30, 198, 242, 245 hormesis, 17, 315 36, 40-42 radiation exposure in tobacco, 3, 4 Sahlgrenska University Hospital, 168 hyperradiosensitivity for low doses, 314 synergistic effects, 242 integration of biology and epidemiology, Salivary gland tumors, 149-150, 161, 165, 167, Socioeconomic status, confounding in radiation 321-322 269 studies, 199 Sarcomas, 67, 69. See also Osteosarcoma; Soft lifetime risk models, 322-323 Soft tissue sarcoma, 80, 84, 161 medical radiation studies, 5, 17, 319-320 tissue sarcoma Solid cancers, 6 molecular and cellular responses to ionizing Sasakawa Foundation, 225 age dependencies, 297-298 Savannah River Site, 190, 192 radiation, 15-16, 313-314 in atomic bomb survivors, 142, 143, 144- multisystem developmental abnormalities, Scaffold proteins, 32, 33, 34 147, 245, 297-307 317 Schwannomas, 152 baseline risks, 241 Scoliosis, 155, 172, 176, 177, 187 occupational radiation studies, 17, 320-321 Chernobyl accident and, 227-228 potential recoverability correction factor, 317 Searle, Tony, 100 n.1 defined, 377 radiation-sensitive subpopulations, 314 SEER (Surveillance, Epidemiology, and End dose-response relationship, 74-75, 142, 144, Results) registry, 242 tumorigenic mechanisms, 17, 315-316 145-146, 201, 245, 298 whole-body CT scan cohorts, 5 Segmental aneusomy syndromes, 112 incidence, 144, 279, 298-307

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404 INDEX medical-use-related risks, 161, 172, 287-289 radiotherapy-related, 12, 157, 159, 160, 163, iodine-131 exposure and, 12, 68, 161, 165, mortality data, 144, 280, 298-307 164, 166, 168, 185, 186, 287, 288, 289 171, 182, 213, 215-226, 233-235, 276 murine studies, 74-75 risk factors, 241-242, 302 latent phase, 215 risk assessment models, 143, 144-145, 241, risk models and estimates, 12, 173, 185, 186, medical-exposure-related risks, 12, 161, 180- 269-271, 279, 284, 287-289, 297-307 215, 269, 272, 275, 278, 279, 280, 282, 182, 234, 287 sex differences, 145, 298 284, 285, 294, 301, 303-306 medullary, 86, 244 spontaneously occurring, 65, 66-67 risk transport model, 241-242 model, 273 sum-of-sites estimates, 279-280, 296 Strontium-90, 212, 213, 214, 269, 276 mortality, 165, 181 vasculature, 66 Superoxide radical, 30, 50 multiplicative model, 244 Somatic cells Swedish benign breast disease study, 26 nuclear facility proximity and, 213, 215, 234, defined, 377 Swedish Cancer Registry, 166 276 DNA repair in, 36 Swedish Family Cancer Database, 88 nuclear weapons tests and, 212, 234, 276 mutagenesis in, 46-47, 66, 113, 127 Swedish infant skin hemangioma patients, 26 papillary, 68 tumorigenesis, 66 Synchrotron radiation, 24 pooled analyses or risks, 181, 268, 287, 295 soxR gene, 36, 37 radiosensitivity of thyroid gland, 173 soxRS transcription factor, 50 radiotherapy-related risks, 157, 159, 161, Specific locus tests T 162, 166, 167, 168, 169, 181-182, 234 dominant mutations in mice, 100-101 relative risk, 244 Spherocytosis, 98 Tcr gene, 68 risk assessment, 181, 244, 268, 270-271, 272, TEC facility, 200 Spondylosis, 165 273, 275, 282, 286, 287 Spontaneous mutations, 91 Televisions, 3 risk estimates, 173, 180-182, 282, 294 clusters, 97 Telomere-like repeat sequence arrays, 69 risk factors, 244 Telomeres, 34, 48, 71-73 dominant disorders, 97-98 sex differences, 161, 167, 181, 244 doubling dose calculations, 8, 96-101, 119 Terrestrial radiation, 43 Thyroid diseases estimation of rates, 97-98 Testicular cancer, 160-161 benign tumors, 225, 244 12-O-Tetradecanolyphorbol-13-acetate (TPA), 75 extrapolation from mice to humans, 96-97 dose-response relationship, 153 frequencies, 47, 94, 102 Tetrapeptide repeats (TPRs), 52 radiotherapy-related risks, 165-166, 169 in genetic risk assessment, 96, 102, 109-111, Therapeutic irradiation. See Medical uses of Thyroid stimulating hormone, 244 radiation; Radiotherapystudies 124-125 Thyrotoxicosis, 166 germinal mosaics, 97 Thorium, 3 Tinea capitis cohorts in human genes, 96-98, 109-111, 124-125 Thorotrast, 68, 150 pooled data for risk assessment, 273 Three Mile Island, 208, 209, 211 mechanisms, 124-125 radiotherapy-related risks, 68, 155, 156, 166- in mice, 96-97, 126 Three-Country Study, 14 167, 181, 182, 183 and natural selection, 94, 102 Thymine glycols, 52 skin cancer, 68 Thymus gland enlargement, radiotherapy risks, paternal age effects, 97 thyroid cancer, 181, 182 point, 47 26, 167-168, 176, 177, 180, 181, 182, Tobacco, 3. See also Smokers/smoking radiation-induced damage compared, 30, 243, 273, 287, 292 Tonsil enlargement, 169 Thyroid cancer 124-125 Topoisomerase, 34 recoverability in live births, 109-111, 124, age and, 167-168, 180-181 TP53 gene, 67-68, 79, 80, 81, 82, 83 125 age at exposure and, 74, 76, 86, 149, 167, Tradescantia, 24 181-182 sex differences, 96-97 Traits, heritability of, 106 Springfields nuclear workers, 191, 192, 195, 196 in atomic bomb survivors, 148, 149, 181, Transcription factors, 51, 53, 66, 67 Squamous cell carcinoma, 67, 80, 151 244, 269, 295 Transforming growth factor-α (TGF-α), 55 BEIR V model, 291-292, 294 Stanford University Medical Center, 159 Translocations State Chernobyl Registries, 203 benign thyroid nodules, 168, 244 cell cycle phase and, 45 Statistical methods in cervical cancer survivors, 181 dose-response relationships, 57, 58, 60, 61 Chernobyl accident and, 68, 72, 203-204, atomic bomb survivors, 143-144 in mice, 57, 58 inference tools, 137-138 215-226, 234-235, 246, 276 nonreciprocal, 48 Statistical power of studies, 136 childhood exposure and, 68, 72, 149, 161, segmental jumping, 72 162, 166, 167, 168, 169, 181, 182, 214, Stem cell spermatogonia, 92, 98, 113, 119, 126, telomeric sequences at, 72 127 215-226, 234, 244, 246, 287 Trichothiodystrophy, 80 Steroid hormone receptor genes, 86 chromosomal aberrations and, 67, 246 Triliated thymidine (3HTdR), 53, 55 coherence of BEIR VII model with other Steroid sulfatase deficiency, 93 Tritium, 200 Stomach cancer. See also Digestive system studies, 287 Trp53 gene, 69, 70 cancer diagnostic irradiation and, 171, 234 TSC1 gene, 80 dose-response relationships, 149, 160, 162, in atomic bomb survivors, 147, 148, 149, Tsc-2 gene, 69, 80 150, 151, 215, 240, 242, 269, 288 167, 168, 169, 182, 215, 224, 225, 276 Tuberculosis patients. See Fluoroscopy baseline lifetime risk estimates, 278 ethnic origin and, 167 Tuberous sclerosis, 80, 82, 83, 98 etiology, 244 in cervical cancer survivors, 158, 185, 288 Tumor progression, 49 childhood exposures and, 168, 185 excess relative risk, 12 Tumor promotion, 240, 241 etiology, 241-242 familial medullary, 80 action of, 241 genetic susceptibility, 80, 81-82, 86, 244, 246 excess relative risk, 12, 287, 288, 289, 301- and dose-response relationships, 75, 76 302 hormones and, 244 environmental/lifestyle factors, 242, 244, 254 incidence, 173-174, 185, 278, 284, 298, 303, in utero exposure and, 224, 225 genes, 66, 68, 80, 81-82 incidence, 180-181, 244 305, 304, 306 hormonal factors, 243, 244 mortality, 278, 282, 298 iodine deficiency and, 225, 244 stomach cancer, 241-242

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INDEX 405 Tumor registries, 141, 142, 147-148, 150, 151, Ultraviolet light Uranium, 2, 3, 20, 269 152 DNA damage, 40 Uranium miners, 190 Tumor suppressor skin cancer, 75, 151 lung cancer, 68, 138, 242 disorders, 80, 84 tumorigenesis, 67-68, 75 risk modeling, 262 genes, 39, 65, 66, 67-68, 69, 80, 80, 81, 82- Uncertainties. See also Bias; Confounding Urinary tract cancer. See also Bladder cancer 83 factors ankylosing spondylitis cohort, 164 Tumorigenesis, radiation induced from age-related effects, 297 atomic bomb survivors, 148, 149 adaptive responses, 12, 51, 52, 62, 78-79, in atomic bomb survivor data, 130, 131, 141, cervical cancer survivors, 157, 158 250-251 147, 172, 285-286 Chernobyl accident and, 223, 227-228 aggressive, 72 cancer risk estimates, 25-26, 147, 174, 251, U.S. Department of Energy, nuclear facilities, alpha particles and, 70 268, 272-273, 275, 276, 278, 279, 280, 190, 198 animals studies, 11, 12, 67, 68-70, 73-79, 82- 284-286, 297, 308-310 U.S. Environmental Protection Agency (EPA), 83, 89, 240 in Chernobyl data, 128, 129, 202-203 274, 275, 282, 283, 293, 294 cell killing and, 12, 74, 75, 76, 82 chromosomal radiosensitivity, 82 U.S. Food and Drug Administration, 5 chromatid instability and, 70-73 combining sources of, 309-310 U.S. Scoliosis Cohort Study, 172 chromosome aberrations and, 24, 46, 66, 68- in cross-population transport, 279, 284, 285, Uterine bleeding disorders (benign), 163-164, 69, 70, 72-73, 74, 82, 86 286, 296 183, 287, 288 confounding stress factors, 71 in DDREF, 279, 284, 285, 286, 295, 296, Uterine cancer DDREF, 77-79, 246-250 310 in atomic bomb survivors, 147, 148, 149, diet and, 242 defined, 377 269, 298, 303-306 DNA damage response and, 6, 11, 65, 68, 69, in diagnostic radiation risk estimates, 286 radiotherapy-related, 157, 158, 159, 162, 70, 73, 82, 83, 239, 227-228, 239, 246 in dose-response relationships, 246 163, 287 dose-response relationships, 12, 45, 50, 55, in dosimetry, 3, 14, 128, 129, 139, 142, 169, risk models and estimates, 272, 278, 279, 59, 60, 61-62, 68, 70, 73-77, 84, 89, 140, 198-200, 233, 241, 266, 285 280, 282, 303-306 245-246 in doubling dose estimates, 98-99, 130, 131 Uterine fibroma, 86 epidemiologic studies, 68 EPA assessment of, 284 Uterine myoma, 151-152, 153 etiology at different histologic sites, 241-245 in epidemiological studies, 133, 284 fractionation kinetics, 73, 75-76, 78-79, 182 in error correction, 296 genetic susceptibility, 12, 65-66, 79-90 in exposure estimates, 114, 174 V genomic instability and, 11-12, 39, 49, 65, in genetic risk estimates, 98-99, 114 66, 67, 69, 70-73 joint analysis, 295 Vaginal cancer, 157 Varicose veins, 95 in hematopoietic cells, 70-71 LAR analysis, 278, 279, 284, 308-310 human data, 68, 71, 83-85 in lifetime cancer risk, 278, 279, 284-286 VHL gene, 66, 80, 81 latency, 65, 68, 78 Monte Carlo analysis, 293, 295 Vinblastine, 130 Vincristine, 130 life-span shortening, 76-77 NCRP assessment of, 284 lymphoma and leukemia, 68-70, 71, 73-74 NIH assessment of, 284, 295 Von Hippel-Lindau syndrome, 80, 125 malignant transformation, 51-52, 62, 78-79 occupational exposures, 14, 194, 198 mammary epithelial cells, 71-73 in population effects, 286 mechanisms, 11-12, 27, 65, 66-70, 74, 75, procedures for addressing, 308-310 W 76, 81-82, 89, 245 quantitative evaluation, 278, 284-285 Warthin’s tumor, 150 monoclonal origins, 11, 245, 253-254 in radiation exposure data, 3, 169 Water, electron ionization, 21, 29-32 mouse models, 68-69, 70, 71 in RBE, 29, 286 World Health Organization, 128 mutations and, 11, 65, 66-70 in risk estimates, 29, 284, 286 WT-1 gene, 66, 80 persistence of initiated cells postirradiation, from sampling variability, 278, 279, 280, 76 284, 285, 296, 308-309 phases and process, 11, 66, 240 sources, 133, 285, 295-296 X in progeny, 70 statistical, 29 quantitative studies, 73-79, 89 time since exposure, 275 Xenon, 209 RBE for, 24, 28, 29 Underground miners. See Uranium miners Xeroderma pigmentosum, 79, 80, 81 solid tumors, 74-75 United Nations Scientific Committee on the X-linked disorders, 79 spontaneous mechanisms compared, 11, 12, Effects of Atomic Radiation XP-A to XP-G gene, 67, 68, 80 66-67, 70, 239 (UNSCEAR), 91, 93 XPV gene, 80 target for, 54 cancer risk model, 138, 240, 268, 272, 274, X-rays. See also Radiotherapy studies telomere sequence instability and, 12, 71-73 275, 277-278, 282-283, 293-294, 297- animal studies, 68, 69, 100-101 temporal projections of risk, 239-240 298, 307 atomic bomb explosion, 22 UV radiation and, 67-68 congenital abnormality frequencies, 112 bystander effects, 54 Twin studies DDREF, 131, 246, 249 cancer risk estimates, 171, 276 of genetic susceptibility to cancer, 88 defined, 377 childhood exposures, 211 of multifactorial diseases, 93 genetic risk calculations, 92, 94, 95, 96, 109, chromosome aberrations, 48, 86 111, 112, 118, 131 correction to gamma rays, 24 lifetime cancer risk estimates, 294 defined, 378 U mutation rate estimation, 109, 111 diagnostic, 3, 4, 5, 6, 21, 22, 156, 171; see occupational exposure studies, 190 also Mammography Ulcer patients United Nuclear Corporation, 190 discovery and early studies, 2 dose-response relationship, 153 DNA damage, 30, 32, 33, 36 Units of dose, xi, 2 radiotherapy-related cancer risk, 163 Uracil, 30 dose-response relationships, 49, 56, 61, 62

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406 INDEX electron tracks, 62 RBE, 22-26, 276, 286 XRCC3 protein, 35, 36 luggage inspection scanners, 3 resistance to, 30, 32, 40, 42 XRCC4 protein, 35 mutations, 68, 91, 99, 100-101 soft, 20, 22, 55, 286 from photoelectric process, 20, 22 spikes, 20 photon energies, 20-22, 23 tumorigenesis, 24-26, 49, 68, 69, 75 Z physical aspects, 19-29 ultrasoft, 22 priming dose, 55, 78 U.S. population exposure, 3, 5 Zinc-65, 200 Zirconium-95, 212, 213, 214 XRCC1 protein, 32, 33, 34 XRCC2 protein, 35, 36