Health Effects of Exposure to Low Levels of Ionizing Radiation BEIR V (1990) / Chapter Skim
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Index A A-bomb survivors age and cancer risks, 5 bone cancer in, 307, 310 brain and nervous system tumors in, 311-312 breast cancer in, 183, 207-212, 222, 223, 253, 255, 257, 266 cancer mortality, 165, 183 cancer risk assessment, 5, 16~165 cataracts in, 363 chromosome nondisjunction in, 84 cohort source and exposure, 162-164, 182-183 colon cancer in, 183, 301-303 Committee's analysis of data, 19~206 confounding in studies of, 46 control group, 162 cytogenetic study of children of exposed parents, 95 data used in this study, 198-200 deaths from cancer, 162, 163 digestive system cancer in, 165, 170, 171 dose-response relationships, 5, 165 dosimetry changes for, 2, 05, 30, 55, 164, 165, 175, 182-183, 19~195, 198, 242, 254, 269, 278 doubling dose for, 69, 72, 75-76, 95-96, 98, 99, 125 esophageal cancer in, 183, 299 excess cancer risk in, 50 extrapolation to low dose rates, 76 extrapolation to other populations, 3, 218 first-generation mortality sample, 9~95 follow-up, 183, 208, 223, 268 genetic risk assessment in, 4, 69, 75-76, 94-97 infant and childhood mortality, 95 intellligence test scores of, 359-360 leukemia in, 22, 165, 183, 24~248 Life Span Study, 163-164, 170, 171, 174, 175, 18~184, 19~191, 194, 196, 207, 219, 229, 242-248, 254, 255, 257, 266, 268, 269, 273, 301, 307, 31~319 liver cancer in, 304 lung cancer in, 15~153, 183, 26~269, 271, 273 malignant lymphoma in, 329 mental retardation in, 7, 355-359 model selection for this study, 200 203 multiple myeloma in, 183, 328 nasal cancer in, 324 neutron RBE for, 165, 19~194 noncancer deaths, 184 organ-specific transmission factors, 19~195 ovarian cancer in, 183, 313 pancreatic cancer in, 333-334 prostate cancer in, 316-317 rare electrophoretic variants in children of exposed parents, 95 401
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402 rectal cancer in, 302, 303 salivary gland tumors in, 331 school performance by, 36~362 sex ratio distortions among, 94 smoking effects in, 272 somatic and fetal effects in, 3, 353, 355-362 stomach eaneer in, 183, 278, 279, 280 strengths and limitations of studies of, 183-184 testicular eaneer in, 315 thyroid cancer in, 281, 286 uncertainties in data from, 162, 163, 165, 183, 222 urinary tract eaneer in, 183, 318-319 uterine eaneer in, 314 Absorbed dose and biological effcet, 24 defined, 11, 12, 24 determination of, 12 measurement of, 11-12 Aetinide radionuelides, 41, 305, 306 Adenoearcinomas, 263, 30~302 Adenomas, 276, 297, 321-323 S-Adenosylmethionine, 36 Alopecia, 42 Alpha particles and bone eaneer, 307-310 and earcinogenesis, 144-145 chromosome aberrations from, 116, 117 dosimetry uncertainties, 20 LET value, 11 and liver eaneer, 305 and lung eaneer, 270-272 mutation rates from, 105, 111 from nonelastic scattering processes, 16 RBE, 105, 111, 116, 144, 145, 309 5-Aminobenzamide, 145 Angiosareomas, 303 Animal studies of bone eaneer, 308 310 extrapolation to humans, 2, 4, 8, 41, 4~44, 67~8 of genetic effects of radiation, 69, 81-82, 97-125 of growth and development effcets, 354-355 on internally deposited radionudides, 41, 42 life-shortening effects of radiation in, 363-364 INDEX liver eaneer, 305 lung eaneer, 275-278 mammary eaneer, 263 prostate cancer, 318 small-intestine eaneer, 300, 301 species differences in particle clearance, 41 Thorotrast toxicity, 304 see also specific animals Ankylosing spondylitis patients bone cancer in, 306 brain and nervous system tumors in' 311-312 breast cancer in, 171 cancer deaths, 184 colon eaneer, 166, 185, 301-302 dosimetry, 165, 184 esophageal eaneer in, 299 follow-up, 184-185, 269 laryngeal eaneer in, 330 leukemia in, 242, 243, 245, 247-248, 249 liver cancer in, 300305 lung cancer in, 171, 268, 269-270 malignant lymphoma in, 329 modeling cancer risk in, 165-166, 169, 17~171 multiple myeloma in, 329 nasal cancer in, 324 ovarian cancer in, 313 pancreatic eaneer in, 333 prostate cancer in, 317 respiratory eaneer in, 169 source of cohort and exposure, 184-185 stomach eaneer in, 280 strengths and limitations of, 185 temporal variations in risk, 162 testicular eaneer in, 315 urinary tract cancer in, 319-320 uterine eaneer in, 314 Antiinflammatory steroidal agents, 138 Antioxidants, 138 Antipain, 24, 145, 147 Ataxia telangieetasia, 35, 37, 151 Auger electrons, 9 Autoerine growth factors, 139 Autopsy data, on internally deposited radionuelides, 41 B Background radiation, see Natural background radiation
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INDEX BEAR Committee, 65 doubling dose method for humans, 7~74, 74 genetic death eoneept, 73-74 BEIR I Committee dominant disorder risks, 77 doubling dose method for humans, 74-75 genetic effects estimation, 68 principles of risk estimation, 67 transloeation risks, 81 BEIR III Committee bone eaneer dosimetry, 307-308 eaneer risk models, 6, 53, 175-176, 200, 201 chromosome nondisjunction risks, 83 comparison with risk estimates in this report, 6, 174-175, 176 dominant disorders in first generation, 77 dose-response model in, 52, 175 doubling dose method for humans, 75-76 DREF estimates, 23, 174 equilibrium excess of irregularly inherited disorders, 85 86 excess cancers from low-LET radiation, 49 extrapolation modeling for animal data, 119 genetic effects estimation, 68, 81 lifetime excess eaneer risk method, 174 liver cancer risk values, 303 lung cancer risk values, 271, 272 mutation rate estimation, 112 neutron RBE, 192 NUREG/CR-4214 results compared with, 82-83 RBE for leukemia, 55 transloeation risks, 81~2 BEIR IV Committee liver eaneer risk estimates, 304, 305 lung eaneer risk assessments, 270-275, 277 osteosareoma risks from, 308 Benign uterine bleeding, urinary tract eaneer in radiotherapy recipients, 320 Bergonie, J., 42 Beta panicles bone eaneer from, 307-309 colon carcinoma from, 302 and liver cancer, 305 lung eaneer studies in animals, 27~277 nasal cancer from, 32~325 4133 thyroid eaneer from, 287 Bile duet carcinomas, 303, 305 Biological damage critical sites for, 13 process during energy transfer, 1~15 RBE, 309 see also Chromosomal aberrations; DNA damage; Genetic effects Bladder eaneer, 183; see also Urinary tract eaneer Bleomyein, 14 Bloom's syndrome, 35, 37, 151 Bone eaneer animal studies of, 308 310 high-LET radiation and, 307-308 human data on, 306 308 latency, 306-307 low-LET radiation and, 30~307 from nuclear weapons tests, 374 temporal distribution of, 52 Brain tumors, 31~313, 374 Breast eaneer in A-bomb survivors, 165, 183, 207-210, 222, 253, 255, 257, 266 additive risk, 208 age-specific rates of, 152, 169-170, 207, 210, 216, 225-226, 258-260, 267 age at exposure and, 169, 21~214, 219, 253, 256-258, 260, 261 animal studies of, see Mammary cancer; and specific animals in ankylosing spondylitis patients, 171 background rates, 207-209, 254, 257 cohort descriptions, 207, 223 cohort effects in risk assessment, 20~212 diet and, 266 dose-response relationships, 211, 212-213, 261-263, 267 in fluorosoopy recipients, 187, 207-209, 211, 212, 253, 254, 255, 262 hormones and, 152, 253, 261, 262, 264-267, 267 incidence and mortality, parallel analyses of, 253-255 latency, 169, 214-216, 224, 226, 257, 260, 261, 267 in mastitis treatment group, 187, 207, 255, 256, 267 menarehe and, 265, 266 menopause and, 265
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404 modeling, 16~170, 20~218, 254, 255-260 mortality, 21~211, 213-214, 256 from nuclear weapons tests, 374 pregnancy and, 265-266, 267 relative risk, 208-217 susceptibility to, 152 type of exposure and, 253, 255, 262, 267 uncertainties in risk models for, 224 Burkitt's lymphoma, 35 C Calcium-45, 308 Canadian fluoroscope study, 186-187, 207-209, 211, 212, 254, 255, 257, 262 Canadian National Mortality Data Base, 187 Cancer acute exposure and, 174, 175 age and incidence of, 135, 152 age at exposure and, 6, 174, 175 categories for this study, 198-199 in childhood following in utero exposure, 352-354 genes, 36; see also Oncogenes inherited predisposition for, 2, 149 latency period, 135, 137, 168 lifetime risks of, 6, 172-173, 174 misclassification of disease status, 45, 48, 50 mortality, 161, 177, 180 around nuclear installations, 37~379 from nuclear reactor accidents, 377 from nuclear weapons testing, 373-377 recessively inherited conditions and, 35, 38 rates, temporal distribution of, 52 sex and, 153, 177, 180 site-specific risks, 174, 175; see also specific sites stages, 135 see also Carcinogenesis; lLmorigenesis Cancer cells chromosome aberrations in, 33, 35 killing with alkylating agents, 38 methyl transferase in, 38 see also Cell cultures; In vitro transformation assays Cancer risk assessment absolute risk model, 53, 200 201 INDEX additive model, 152, 162, 163, 166, 201, 202, 248, 254, 285 age-specific, 166, 201, 219, 248 all sites, 161-238 alternative models, 6, 203-206 baseline mortality data, 171, 219 for bone cancer, 52 cohort effects in, 20~212, 24~241, 284-285 cross-over dose in, 234 data used for, 198-200 diagnostic examination of models, 197, 227-234 dose-rate effectiveness factor in, 22, 23, 220, 23~238 exclusion of high doses in, 199-200 extrapolation of animal data to humans, 43 extrapolation of high dose rates to low dose rates, 171, 174 human data for, 2; see also Epidemiological studies; Human studies for leukemia, 22, 52, 200 lifetime risk, point estimates, 6, 50, 162, 163, 165, 171-181 model selection for this study, 20~203 probability of causation in, 224 227 probability tables for, 50 relative risk model, 5-6, 53, 152, 162, 168, 197, 200 203, 208 212, 248, 254-260, 285 sex adjustments in, 201, 219 stratified-background relative risk model, 201-202 temporal variations in risk, 162, 219 uncertainty in, 162, 17~181, 217-224 see also A-bomb survivors; Model fitting; Models/modeling; Risk assessment; and specific cancer sites Capture reactions, 1~17 Carcinogenesis age and, 135, 15~153 alpha particles and, 144-145 benign growths converted to malignancies, 139 chromosome aberrations and, 21, 35 dose fractionation and, 141-142 dose incidence ratios, 43 dose protractions and RBE in, 28 and dose-rate effects, 22, 141-142
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INDEX dose response, 21, 136, 140-141 genetic polymorphism for metabolism of carcinogens, 151 and gene expression, 136, 138, 239 genetics of, 136, 145-152 and hereditary fragile sites, 151-152 hormones and, 139 initiation, promotion, and progression in, 13~139, 152 irreversibility of, 136 LET of radiation and, 21, 142-144 mechanisms of radiation induction of, 7, 136-145 modifiers of, 24, 139, 145, 15~153, 161, 183 mortality rates, 135 multistep process, 135 mutational steps in, 135, 136, 137-138, 145, 147 protooncogenes, 147-149 radiobiological factors affecting oncogenic transformation, 139-140 RBE variation with LET for, 21, 29, 31 recessive breakage and repair disorders, 151 sex and, 15~153 smoking and, 15~153 somatic mutation theory of, 136 thyroid cancer phases, 295-297 tissue irritation and, 138 tumor progression, 137 tumor-suppressor genes, 149-150 Carcinogens genetic polymorphism for metabolism of, 151 Cataracts, 78, 103, 124, 363 Cell cultures chromosome breaks in irradiated lymphocytes, 33 see also In vitro transformation assays Cell killing/lethality by alpha panicles, 144 and cell cycle phase, 22 chemical modification of radiation effects, 23-24 dose-rate effects on, 22, 110 dose-response relationships, 20-21, 51 oocyte sensitivity to, 98, 112, 113 by neutrons, 144 RBE variation with LET for, 21, 27-28, 29, 31, 143 405 target for, 20 Cerium-144, 42, 302, 305 Cervical cancer patients bone cancer in, 306 colon cancer in, 301 esophageal cancer in, 298-299 leukemia in, 245-246, 249 liver cancer in, 305 lung cancer in, 270 malignant lymphoma in, 329 ovarian cancer in, 313 pancreatic cancer in, 333 radiotherapy cohort, 185-186, 245-246, 270, 279, 298-299, 32~321 rectal carcinoma in, 302 small-intestine cancer in, 300 stomach cancer in, 279 and urinary tract cancer, 320-321 uterine cancer and, 314 Cervical tubercular adenitis, 321-322 Cesium-137, 42, 110, 261, 262, 305 Chemical effects of radiation, 12-15 Childhood/children brain and central nervous system tumors in, 31~311, 312 breast cancer in women exposed during, 261 cancer risks in, 6, 352-354 cancer risk estimated for, 201-203, 219 in utero radiation exposure, 8, 247, 310-311 leukemia in, 203, 247, 373-375, 376 respiratory tract cancer in, 169 thvmus eland radiography in infancy, 326 thyroid cancer in, 281, 283-286, 298 Cholangiocarcinomas, 303 Chromatid aberrations, 33, 82, 105, 114, 117, 118 Chromosome aberrations age and, 83, 118, 122 aneuploidy, 84, 124, 139 balanced, 106 breaks, 33, 35, 37, 119, 151 and cancer, 33, 35 and cell stage in spermatogenesis, 117 deletions, 33, 34, 35, 98, 117-119, 122-123, 149-150 bicentric, 21, 33, 34, 119 and dose of radiation, 33, 34, 84, 116-117, 118 double minute chromosomes, 35, 149
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406 fragments, 118, 119 heritable fragile sites, 34 35, 151-152 homogeneous staining regions, 35 interchanges, 118 inversions, 108 linear-quadratic formulations from, 21 in mammals other than mice, 118-120 during meiotie stage in gametogenesis, 119-120 in mice, 114-118 monosomy, 35 from natural background radiation, 384, 385 nondisjunction, 83~4, 122, 150 oncogene activation, 21, 148 RBE for, 26 rearrangements, 3~35, 117, 118, 120, 148, 151 screening for, 114-115, 117-118 somatic, 35 spontaneous frequencies of, 91, 92, 118 trisomy, 32-33, 83 84 from tumor promoters, 139 W-induced, 35 see also liansloeations Cigarette smoke, see Smokers/smoking Cobalt-60 LET value for electrons, 11 RBE of, 26 spermatogonial mutation rates from, 103, 110 Colon cancer, 166, 183, 185, 301-302 Compton scattering, 9, 10, 11 Congenital disorders doubling dose for, 99 in mice, 103, 120-121 rates of induction, 120-121, 123 risk estimates for, 86~8 spontaneous frequencies of, 91, 92 Consumer products radiation, U.S. population exposure to, 17, 19 Cosmic radiation, 19 Cyclobutane pyrimidine dimer, 36 D Death certificates lung cancer mortality data, 273 reliability of data from, 45, 165, 19~199, 218, 304, 316, 319 INDEX Dental radiography, meningiomas from, 312 Dermatitis, 42 Development, see Growth and development effects Diagnostic radiography adult-onset myeloid leukemia from, 247, 371-373 brain and central nervous system tumors from, 310-311 in utero, 247, 310-311 salivary gland tumors from, 331 and thyroid cancer, 287, 288 289 see also Medical uses of radiation Diet, and heart disease, 90 Digestive system cancer in A-bomb survivors, 165, 170, 171, 194, 280 281 age and, 170, 224, 280-281 deaths from, 282 risk model for, 224, 231-234, 280-281 sex and, 280-282 uncertainty in risk models, 224, 231-234 see also Colon cancer; Esophageal cancer; Rectal cancer; Stomach cancer DNA damage adenine deamination, 36, 37 approximation of, 13-14 apyrimidinie site, 37 assessments of, 1~15 base removal, destruction, or mutation, 36-37 chain breakage, 37 eytosine deamination, 36, 37 deo~yribose residue destruction, 37 from free radicals, 139 guanine methylation, 36 individual moieties, 14 intracellular, causes, 14 ligase deficiency, 37 local energy deposition in, 15 locally multiply damaged sites (LMDS)
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7 organ, 191-192, 194, 199 protracted, see Protracted exposure and RBE, 31 summing doses of different-quality radiations, 25 temporal patterns of distribution, 3~39 uncertainties in estimates of, 222 see also Absorbed dose; Effective dose equivalent; [issue dose; Total dose Dose fractionation and bone cancer, 306 and breast cancer risk, 255-256, 262, 267 and carcinogenesis, 6, 7, 141-142, 187 and chromosome aberrations, 116-117, 121 and damage repair, 118 and leukemia risk, 245, 251 and mutation rates in spermatogonia, 111 and radiation injury, 23 RBE variation with, 28, 3~31, 144 and skeletal abnormalities in mice, 103 Dose rate and mammary cancer, 262 and carcinogenesis, 141-142 and cell lethality, 22 and chromosome aberrations, 34, 117, 118 and dose-rate effectiveness factor, 23, 25 extrapolation of low doses from high doses, 76, 161-162 and mutation rate, 105-107, 110, 124-125 and RBE, 26, 31 sex differences in effects, 98 Dose-rate effectiveness factor (DREF) from animal data, 23 bias and variance of sample estimate of, 230237 extrapolation of acute exposures to low dose rates, 171, 174, 220 factom affecting, 23 for leukemia, 22, 234 237 measure of, 234 sex differences in, 113 Dose-response relationships for A-bomb survivors, 5, 165 for breast cancer, 211, 212-213, 262, 264, 267 for carcinogenesis, 21, 14~141, 146, 165 and chromosome aberrations, 33, 119
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408 for congenital abnormalities, 120 for DNA chain breaks, 37 in exposure-time-response models, 51 for internally deposited radionuclides, 38-39 in laboratory animals, 5 for leukemia, 200, 234-237, 242-243 and LET of radiations, 5, 20-21 linear, 72, 175, 243 linear-quadratic formulations, 20-21, 75, 262 mutations, 44 noncancer deaths, 184 and RBE, 21, 24, 29 single-track effects with repair factor, 21 temporal relationships in, 5, 211 for thyroid cancer, 284 286 and tumor promoters, 24 Dosimeters, biological, 33-34 Dosimet~y of ionizing radiation for A-bomb survivors, 4-5, 20, 164, 175, 182-183, 190-195, 198 for ankylosing spondylitis cohort, 184 cervical cancer treatment cohort, 185 DS86 system, 96, 164-165, 175, 190-195, 198, 211, 222, 242, 243, 254, 269, 304, 315, 316-318, 319 fluoroscope studies, 186, 188 Monte Carlo simulations, 184, 186, 188 neutron component, 164 postpartum mastitis study, 187 T65D, 96, 175, 190 194, 198, 268, 272, 299, 3W, 316, 318-319 uncertainties in, 222, 224, 270 see also Microdosimetry; Physics of ionizing radiation Doubling dose from A-bomb survivor data, 69, 72, 75-76, 95-96, 98, 99, 125 acute, 95 basis for, 71-73 BEAR Committee estimates, 74 BEIR I Committee estimates, 74-75 BEIR III Committee estimates, 75-76 confidence limits of, 95-96 for congenital malformations, 99 definition, 72 dose rate and, 125 extrapolation from mice to humans, 4, 7S first-generation mortality and, 76 gametic, 72, 73, 95 INDEX for increase in mutation rates, 71-72 for mice, 72, 75, 95, 98-99, 102, 125 minimum, 97 point estimate, 75 pregnancy outcome and, 76 sex-specific, 72 uncertainties in, 76 zygotic, 72, 73 Down syndrome, 3~33, 34, 83-84, 384, 385 Drosophila melanogaste'; 42, 81, 97, 122 E Effective dose equivalent calculation, 17-18 for partial body irradiation, 18 by source of radiation, 18-19 uncertainties in, 1~20 Elastic scattering, 16, 17 Electrons binding energy, 10 hydrated, 12 spectral distributions and LET, 11 Energy absorption chemical effects following, 12-15 see also Absorbed dose Energy transfer processes of low-LET radiation, 9-12 biological damage process during, 13-15 of high-LET radiation, 15-17 direct effects of, 13, 20 indirect effects of, 13, 20 Epidemiological studies adult-onset myeloid leukemia, 371-373 ankylosing spondylitis, 184-185 breast cancer, 207 Canadian fluoroscope study, 18~187 cancer in childhood following in utero exposure, 35~354 case-control, 4708, 49 cervical cancer treatment cohort, 185-186 confounding in, 46, 48, 50 control group, 48 ecological, 47 48 extrapolation of risks from, 46, 47, 50 fallout from nuclear weapons testing, 373-377 high-dose studies, 44-46
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population, 17-20 see also Protracted exposure F Fallout, see Nuclear weapons testing Familial polyposis coli, 149 Faneoni's anemia, 35, 151 Fertility, 364-366 409 Fetal effects of radiation, see Somatic and fetal effects of radiation Fibroadenomas, 262, 263 Fluoroseopy and breast cancer, 253, 255, 257, 262 Canadian epidemiologieal study, 186-187, 207, 211, 212, 254, 255, 257, 262 Massachusetts epidemiological study, 188, 212 Folate deficiency, 35 Free radicals DNA damage from, 139 production during energy transfer processes, 13, 20 tumor promoter induction of, 139 G Gamma rays action producing biological damage, 20 from capture reactions, 17 eareinogenesis, 141, 143 chromosome aberrations induced by, 118, 119-120 cataracts in mice from, 103 cobalt-60, 11, 26 deexeitation, 16 dose-rate effcet, 17, 106, 141 dosimetIy for A-bomb survivors, 5, 191-193 extrapolation to x-ray exposures, 218 kerma, 191, 194 high-energy, 31 mutations in mice from, 77-78, 103, 105, 106 photon energies, 10 RBE of, 26, 30, 55, 82, 220 spatial rate of energy loss, 11 Gene expression, and carcinogenesis, 136, 138, 139 Genes Characteristics, 32 protooneogenes, 147-149 tumor-suppressor, 149-150 Genetic effects of radiation age of onset, 88 animal studies of, 67, 97-125 background data from humans, 9~97 detection of, 66-67 difficulties in measuring, 66 estimates of, 68, 7~71 multifactorial disorders, 3, 8, 92
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. Julnea pigs INDEX chromosome aberrations in, 118 mammary cancer in, 253 particle clearance from pulmonary regions, 41 sex differences in mutation rates, 105 H Hamsters carcinogenic effects of alpha radiation in, 138 chromosome aberrations in, 118 sex differences in mutation rates, 105 Heart disease, mutational component of, 90 He ma ng iosarcom as, 303 , 305 Hepatic cell carcinomas, 303, 305 High-LET radiation and bone cancer, 307-308 carcinogenesis, 143 damage mechanisms, 51 dose-rate effects, 22, 28 dose-response curse for, 25, 26 epidemiological studies, 44-46 mutation rates from, 105 physics and dosimet~y of, 15-17 protracted exposure, 57 RBE for, 105, 121 see also Alpha particles; Neutrons HLA histocompatibility complex, 88-89 Hormones, 24 and breast cancer, 253, 262, 264 267 and carcinogenesis, 139, 145 and thyroid cancer, 282, 287, 29~298 Human genome, 31-32, 38 Human studies of bone cancer, 306 308 of growth and development effects, 355-362 inadequacies for risk assessment, 43 intelligence test scores, 359-360 of internally deposited radionuclides, 41 liver cancer, 30~305 of leukemia, 24~247 of mental retardation, 355-359 school performance, 36(}362 sources of, 2 see also Epidemiological studies Hydrogen peroxide, 14 Hydroxyl radical
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INDEX production during energy transfer processes, 12-13 damage mechanisms of, 13 Hydroxyurea, 137 Hyperthyroidism, 318, 321-323 Hypopharyngeal cancer, 33~331 Hypothyroidism, 282, 288, 295, 296 In vitro transformation assays advantages of, 13~140 of alpha particles, 144-145 application to whole organisms, 141 BALB/3T3 cells, 144 C3HlOT1t2 cells, 141, 143, 144-145 classes of, 140 dose protractions in, 28 dose-response relationships in, 141, 143, 145-146 focal assays, 140 of neutrons, 143-144 NIH/3T3 cell transfection system, 148 oncogene activation in, 149 rat thyroid and mammary cells, 14~141 RBE in, 28, 31, 143 short-term, 140 suppression of, 138, 147 see also Cell cultures Inelastic scattering, 16, 17 Internally deposited radionuclides animal studies of, 277 dose-modifying factors, 38, 4~41 dose rates, 38 dose-response relationships, 38, 40 effective dose equivalent from, 19 liver cancer from, 305, 306 metabolic and dosimetric data, 40 response modifying factors, 41-42 routes of intake, 40 thyroid cancer from, 287-294 International Commission on Radiological Protection, 21, 40, 271 Iodine-131, 41, 42 and prostate cancer, 318 and parathyroid neoplasia, 323 and salivary gland tumom, 331 and thyroid cancer, 287-294, 298 and urinary tract cancer, 321 Ionizing radiation chemical effects following energy absorption, 12-15 411 direct effects of, 13, 14 effieienc~r of cell killing, 14 electromagnetic, 9; see also Gamma rays; X rays fractionation pattern, see Dose fractionation genetic effects of, 2, 31-38 indirect effects of, 13, 14 late effects of, 1 particulate, 9 physics and dosimet~y of, ~17 sensitivity to, species differences in, 68, 76 sensitization to, 35 sources, 1, 17 U.S. population exposure, 17-20 Israel Tinea Capitis Study, 28~286, 298, 362 K Kerma defined, 12 determination of, 12 FIA, 190, 191 neutron, 16~165, 191 Klinefelter syndrome, 34 L Laboratoly animals see also Animal studies; and specific animals Lanthanide radionuclides, 41 Laryngeal cancer, 330 331 LET, see Linear energy transfer Leukemia in A-bomb survivors, 22, 165, 183, 242-248 acute lymphatic, 311 acute myeloid, 243, 245 adult-onset myeloid, 247, 371-373 age and, 167, 203, 224, 246, 248-249, 253 analysis of human data on, 247-250 animal studies of, 25~252 BEIR III risk estimates, 175, 176 chromosome aberrations and, 35 chronic granulocytic, 247 chronic lymphatic, 245 chronic lymphopytie, 243 chronic myelopytie, 35 cross-over dose, 23~238
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412 deaths, 178-180, 242-244 developmental effects of radiation treatment of, 362 diagnostic irradiation and, 24~247 dose-rate effectiveness factor, 22, 171, 223, 234-238, 248 dose response, 200, 234-237, 248, 250, 251 from global fallout, 376 granulocyte precursors, 251 human data, 242-247 latency period, 167, 219, 224, 248, 249, 252 model, 167-168, 171, 247-249 myeloid, 246, 250-252 myelomonocytic, 151 monocytic, 247 from nuclear reprocessing plants, 377-378 from nuclear weapons tests, 37~375 in radiologists, 247 RBE for, 55 risk assessment for, 22, 52, 167-168, 171, 178-180, 234-237, 247-249 risks of, 242-253 sex differences in, 17~180, 219, 243 T-cell, 250 temporal distribution of, 52 uncertainties in risk assessment, 224, 231-238 x-ray treatments for benign gynecologic disorders and, 246 Life expectancy, 363-364 Linear energy transfer (LET) and carcinogenesis, 142-144 and cell lethality, 2~21 defined, 11 as a measure of radiation quality, 26-27 microdomimetric analogue to, 11 for quantitative predictions, 26 variation of RBE with, 27-28 see also High-LET radiation; Low-LET radiation Linear-quadratic models with cell lethality as endpoint, 20-21 for dose-rate effectiveness factor estimates, 22-23, 171 for oocyte response to x rays, 112 origins, 21 RBE derivation, 26 Liver cancer INDEX animal studies of, 305 death certificate data for, 199 human studies of, 303-305 latency period, 303-304 Long-acting thyroid-stimulating protein, 287, 295 Low-LET radiation age at exposure and cancer risk, 53-54 and bone cancer, 306-307 carcinogenic effects, 141 damage mechanisms, 51 dose-response curve for, 25, 26, 30 dose-response relationships for cell lethality, 2~21 dose-response relationships for lesions, 51 epidemiological studies, 4~49 human risk estimates for, 30, 42, 4~47, 49 mutation rates from, 98, 100, 105, 106, 110 protracted exposure, 5~57 RBE variation with dose rate, 22 sources of, 47 see also Gamma rays; X rays Lung cancer, 50 in A-bomb survivors, 15~153, 183, 26~269, 271 additive risk model, 152-153, 271 age and, 239, 240, 269, 274 age at exposure and, 269, 274 and alpha particle exposure, 152 animal studies of, 275-278 in ankylosing spondylitis patients, 171, 268, 269-270 in cervical cancer patients, 270 chromosome aberrations and, 35 comparison of risk estimates by other groups, 271 deaths, 268, 269, 271 dosimetIy, 269-270, 276 lifetime risks of, 240, 271-272 from polonium-210 in tobacco, 19 pulmonary adenomas in mice, 124 from radon, 53, 239-241 risk estimates, 267-278 sex and, 153, 274-275 small-cell carcinoma, 35, 149 smoking and, 45, 53, 152-153, 272-275 uncertainties in risk assessments, 24~241
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INDEX in underground miners, 196, 239, 270-272 see also Respiratory tract cancer Lymphoid neoplasia, 151 Lymphoma malignant, 329-330 murine, 147, 149 Mammary cancer M dose and, 261, 262, 267 hormones and, 261, 263 latency, 263, 267 neutrons and, 263-264 oncogene, 149 in rats, 261-262 see also Breast cancer; and specific animals Mammary tumor virus, 149 Marmoset translocation rates in, 119, 124 x ray effects in, 81-82, 83 Massachusetts fluoroseopy study, 188, 207-209, 212, 254, 255 Mastitis patients breast Cancer in, 255, 256, 267 epidemiologieal study, 187-188, 207-209, 213, 254 Maternal radiation, effects of, 84 Mathematical models, see Models/modeling Maximum likelihood principle, 54, 166, 168, 221-222, 237-238 Medical uses of radiation biological effects in patients, 41, 281 and bone sarcoma, 306 brain and central nervous system tumors from, 310-312 and chromosomal breaks, 33 doses from, 66, 222 epidemiologieal studies of exposure, 45, 46, 371-373 ovarian irradiation, 300, 301 parathyroid cancer from, 321-323 prostate cancer from, 318 rectal Cancer from, 302 salivary gland tumors from, 331 sources of, 19, 65 small-intestine cancer from, 300 thymus gland enlargement, 326 413 and thyroid cancer, 281, 287, 288, 298 U.S. population exposure to, 17, 18, 19, 47 see also Diagnostic radiography Meningiomas, 35, 311, 312 Mental retardation, 3, 7, 8 dose-response models, 35~358 dosimetry, 355 gestational age, 355-356 Methyl transferase, 37-38 Metropathie hemorrhagiea, 301, 320 Mice age-related responses to radiations, 113-114 BALB/e, 114, 262, 263-264 Cataracts in, 78, 103, 124 chromosome aberrations in, 114-118, 121-123 chromosome nondisjunction from, 84, 122 colon carcinoma in, 302 complex traits, 120-125 congenital abnormalities in, 103, 120-121 DBA12, 114 dominant lethal mutations in, 104-107 dominant mutations in, 101, 103-104 doubling dose for, 4, 72, 73, 75, 95, 9~99, 102, 125 extrapolation of data to humans, 2, 4, 75, 95-96 females, mutation studies in, 104, 112-113, 117-118 genetic effects of radiation in, 101, 10~118 hepatie turnover of actinide and lanthanide radionuclides, 41 heritable transloeations ins 121-122 induced mutation rates in, 97 leukemia in, 250-251 lung Cancer in, 276 lymphoid neoplasms in, 329-330 males, mutation studies in, 103, 11~111, 115-117 mammary cancer in, 253, 262, 26.~264 multiloeus deletions in, 122~123 oneogenes, 149 ooeyte sensitivity to cell killing, 98 ovarian tumors in, 313 particle Clearance from pulmonary regions, 41 pulmonary adenomas in, 124
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414 recessive autosomal lethal mutations in, 107-108 recessive visible mutations in, 108-113 rectal carcinoma in, 30~303 sensitivity to mutations, 69 sex-linked lethal/detrimental mutations in, 108 skeletal abnormalities, 73, 77-78, 101, 103, 124 small-intestine carcinomas, 300, 301 teratogenesis in, 4~43 tester stocks for speeifie-loeus tests, 78, 109, 111, 114 traits influenced by new mutations, but not analyzable for risk, 123-124 Microdosimet~y principles, 11-12 and radiation quality, 27 Midonidazole, 303 Model fitting AMFIT program, 54, 166, 196-197, 254, 283 breast cancer data, 169-170 deviance and, 22~230 digestive cancer data, 170 to epidemiologic data, 54-55 Freeman key residual, 228-235 leukemia data, 167-168, 248 maximum likelihood estimates, 54, 166, 196, 221-222, 236, 237-238 methods, 163-166 Newton-Raphson algorithm, 196 nonleukemia cancers, summing of, 170-171 other-cancers group, 170 Pearson ehi-squared residual, 22~230 Poisson regression methods, 54, 166, 196, 227-228 preferred risk models, 167-171 respiratory cancer data, 168-169 statistical methods, 166 167 test of fit, 167, 227-232 uncertainties from, 176, 22~224 Models/modeling A-bomb survivor data, 163-165, 20~206 additive risk, 152, 162, 163, 166, 176, 211, 248 age-at-exposure effects, 169, 213-216, 223 background rates of cancer, 167, 207-208 breast cancer, 169-170, 206 217, 255-260 INDEX cell killing terms in, 251 cigarette smoking effects, 27~273 cohort effects under relative risk and additive risks, 208-212 confidence limits, 167 eonstruetion, approaches, 51-54 diagnostics, 55, 197, 227-234 digestive cancer, 170 dose-response, 50, 51-52, 21~213 exposure-time-response, 5, 51, 56, 166, 180 extrapolation from high dose to low dose, 44, 171 extrapolation from one population to another, 3, 46, 186, 188, 218, 222 extrapolation of animal data to humans, 119 leukemia risk, 167-168 logistic, for probability of disease, 51 multivariate, 50-51 need for, in risk assessment, 4~51 nested alternative models, 167 preferred risk models, 167-171 probabilities of causation, 22~227 proportional hazards, 51, 272, 277, 309-310 see also Cancer risk assessment; Genetic risk assessment; Uncertainties in risk assessment Monte Carlo analysis extrapolation of individual organ doses, 184, 186, 188, 269-270, 317 of radiation field within Japanese houses, 190 of uncertainty in cancer risk, 57, 168, 177-180 Multiple dystrophy, 32 Muller, H J., 42 Multiple myeloma, 183, 327-329 Mutagenesis at apyrimidinic site, 37 and cell cycle phase, 22 of chronic irradiation, 98 dose protractions and RBE in, 28 and dose-rate effects, 22, 98 mechanisms in, 36 RBE variation with LET for, 21, 28, 29, 31 Mutation rates age and, 105-106, 11~114 and cell stage, 105, 122
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population exposure to, 17, 1~19, 47 in Yanjing County, Guangdong Province, People's Republic of China, 38~385 Nervous system, cancer of, 31~313 Neuroblastoma, 35 chromosome aberrations and, 35 oncogene activation, 149 Neurospora species, 122
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From page 416... ...
population radiation exposure from, 19 Nuclear membrane damage, 13 Nuclear workers epidemiological studies of, 379-383 multiple myeloma in, 329 prostate cancer in, 317 Nuclear weapons testing, 47, 65 British tests, 375 Canadian studies, 375-376 cancer among participants in, 375-376 cancer among residents downwind of test site, 373-375 global fallout, cancer from, 291-292, 376 and thyroid cancer, 281, 287, 289-292 U.S. tests, 375 NUREG/CR-4214 dominant disorders in first generation, 7~79 genetic risk estimates in, 82-83 o Occupational radiation exposure bone cancer from, 307 and chromosomal breaks, 33 effective dose equivalent of U.S.
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From page 417... ...
population, 1~19 and lung eaneer, 53, 275 response-modifying factors, 41-42 sources of, 1, 19 uncertainties in exposure estimates, 1~20 see also Underground minem Radon-220, 270 Radon-222, 41, 270 Radon-224, 41, 307-308 Radon-226, 41, 42, 307-309, 324-325 Radon-228, 307-308, 324 Rats ACI strain, 262, 263 Ce-144 in, 42
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From page 418... ...
of alpha particles, 105, 111, 116, 144, 145, 276-277, 309 of beta particles, 276-277, 309 and biological system or endpoint, 29 and cell cycle phase, 22 and compensatory cellular proliferation 22 correction from x rays to gamma rays, 82 and dose rate and fractionation, 28, 30-31 dose-rate effects on, 22, 31 dose-response relationship, 24 factors affecting, 26-29 and LET of radiations, 11, 18, 21, 24-28, 143; see also High-LET radiation; Low-LET radiation limiting value of, 31 maximum at minimal doses, 26 need for concept of, 29-31 for neutrons, 31, 33, 55, 103, 105-107, 111, 113, 116, 121, 125, 142, 14~144, 164-165, 191, 192, 194, 199, 250, 254, 263 for oncogenic transformation, 143 problem with standard for, 26 and protracted exposure, 31, 116 and repair of sublethal damage, 22 variation in relative risk models, 199 Rectal cancer, 302-303 INDEX Renal carcinoma, chromosome aberrations and, 35 Research recommendations carcinogenesis mechanisms, 7 carcinogenicity of low doses and high doses, 8, 307 complex genetic disorders, 8, 71 effectiveness of dose fractionation or protraction, 7 extrapolation of animal data to humans for genetic risk assessment, 8 mental retardation, 8 neutron effectiveness, 7-8 Respiratory cancer age and, 273, 274 age at exposure and, 219, 224, 273-274 dose and, 268 latency, 273 model, 168 169, 273 mortality in A-bomb survivors, 165 sex and, 169 uncertainty in risk models, 224, 231-234 see also Lung cancer Reticulum cell neoplasms, 251-252 Retinoblastoma, 32, 35, 136 chromosome aberrations in, 149-150 gene clone, 150 and osteosarcoma of the orbit, 150 Retinoids, 138 Rhesus monkeys, translocation rates in, 119 Risk assessment animal studies applied to, 43, 55 confidence intervals, 54-55 goodness~f-fit test, 54, 57 internally deposited radionuclides, 38 39 lifetable analyses, 6, 56, 57, 171, 180 lifetime risk projections, 5~57 methodology, 49-57 models, need for, 49 overestimates in, 41 pooling data from multiple studies, 55 RBE in, 55-56 sample sizes for, 49-50 uncertainty of estimates, 57 underestimates in, 45 validity of estimates, 46 see also Cancer risk assessment; Genetic risk assessment; Models/modeling Rochester Thymus Study, 28~286
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From page 419... ...
INDEX S Salivary glands, cancer of, 331-333 Sarcomas, in rats, 42 Selenium, 145 Sinuses, eaneer of, 324-325 Sister chromatic exchanges, 35, 139, 151 Skeleton, see Bone eaneer Skin eaneer, 325-327 in radiologists, 42 xeroderma pigmentosum and, 35, 36 UV-induced, 146 Small intestine, eaneer of, 300 301 Smokerslsmoking bias in epidemiologieal studies from, 45 and carcinogenesis, 138, 152-153 confounding in radiation studies, 46, 270, 299 and heart disease, 90 and lung eaneer, 45, 53, 272-275 radiation exposure in tobacco, 19 synergistic effects of, 53 Somatic and fetal effects of radiation animal studies of, 354-355 eaneer in childhood from in utero exposure, 352-354 cataracts of eye lens, 363 epidemiologieal studies, 8, 352-354 fertility and sterility, 364-365 growth and development, 354-362 human studies of, 355-362 intelligence test scores, 359-360 life shortening, 36~364 mental retardation, 88, 355-359 Spallation process, 17 Spatial energy distribution, 11; see also Linear energr transfer Specific energy, defined, 11 Specific locus test, 97, 98 on female mice, 112-113 on male mice, 11~111 for multiloeus deletions, 122 for recessive visible mutations, 108 113 for spontaneous mutations, 125 tester stock, 109 value of, 109-110 Spontaneous mutations for dominant disorders, 79, 103 and doubling dose, 72 estimation of rates of, 75, 79, 92-94, 98, 99, 112, 125 in female mice, 112 419 genetic burden, 91~92 in humans, 66, 75, 90 92 intragenie, 122 recessive lethal, 81 for seven-locus tester stock, 110 Sterility, 3~366 Stomach eaneer, 183, 27~281; see also Digestive system cancers Strontium-90, 42, 308 310 Suicide enzymes, 37-38 Sulthydryl compounds, 24 Swine, leukemia in, 251 T Teratogenesis, 42 Terrestrial radiation, 19 Testicular eaneer, 315-316 12-O-Tetradeeanoyl phorbol acetate, 145, 146, 147 Therapeutical irradiation, see Medical uses of radiation; and specific cohorts Thorium-228, 42 Thorotrast, 41, 247, 30~305, 324 Thyroid eaneer acute phase, 295-296 additive versus relative risk models, 285 age and, 281, 298 age at exposure and, 285 animal expenments, 293 background rates, 283, 288, 291 benign thyroid nodules and, 282, 290 cohort effects in risk assessment, 284-285 dose-response relationships, 284-286, 293 ethnic origin and, 286 from external radiation, 281, 28~286, 298 histopathology, 282, 297 hormones and, 282, 287, 294-298 human studies of, 287-293 from internally deposited radionuclides, 287-294, 298 latent phase, 285-286, 288, 296-297 model, 286 NCRP Specific Risk Estimates, 293 from nuclear weapons tests, 374 physiology of, 29~295 sex and, 281, 285, 298 tumor growth phase, 297 Thyroid hormones, 145, 287, 294, 296 Thyrotoxieosis, 287, 288
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420 Tinea eapitis cohorts brain and central nervous system tumors in, 311 salivary gland tumors from, 331 skin cancer in, 325-326 somatic and fetal effects in, 362 thyroid cancer in, 283-286, 298 Tissue dose, capture of low-energy neutrons and, 16-17 Total dose, nonelastic scattering and, 16 Traits complex, 120 irregularly inherited, 84-90 liability, heritability of, 86-88 with quantifiable rates of induction, 120-123 liansloeations age and, 116 balanced, 82, 106, 107, 115, 121 eaneer-associated, 15100152 disorders caused By, 35, 115 dose and, 33, 110, 111, 115-117, 121 first-generation and equilibrium effects of, 81-82, 83 heritable, 115, 121-122, 123 kinetics of induction, 115 in mammals other than mice, 118-119 methods for estimating rates of, 68 in mice, 115-116, 125 oncogene activation, 21, 148 and prenatal losses, 115 rates of induction, 68, 115, 117, 121, 124 reciprocal, 23, 35, 68, 118, 121 Robertsonian, 83 spontaneous rates of, 115, 116, 121 in stem cell stage, 106, 107 tumor-specific, 35 llibondeau, lo, 42 Tuberculosis patients, see Fluoroscopy studies Humor promoters action of, 137, 139 defined, 24 and dose-response relationships, 24, 145, 146 and RBE of neutrons, 31 sex differences in exposure to, 153 lUmorigenesis chromosome aberrations and, 35 dose-rate effectiveness factor for, 23 malignancy over time, 136-137 INDEX mutations and, 123-124 in small mammals, 23 RBE for, 26, 29 uniform versus nonuniform x-irradiation, 276 lbrner syndrome, 34 loin studies, of irregularly inherited disorders, 87-89 U Ulcer patients, stomach cancer following radiotherapy, 279 Ulcerative colitis, 302 Ultraviolet light albino sensitivity to, 151 ehromosomal aberrations from, 35 DNA damage from, 36 skin Cancer from, 146 Uncertainties in risk assessment from A-bomb survivor data, 162, 165, 183, 218 from age-related effects, 213, 219, 223-225 in cause of death, 45, 165, 198-199, 218, 304, 316 credibility interval, 220-221, 222, 226 in cross-over dose, 234-238 in dose-rate effectiveness factor, 234-238 in dose-rate reduction factor, 82 and dose-response curve shape, 220 in dosimet~y system, 222, 224 in doubling dose estimates, 76 external to parametric model, 180, 222-223 in genetic risk estimates, 4, 69 as geometric standard deviation, 220, 224, 226, 227 in irregularly inherited disorders, 85-86 from latency, 219, 22~225 and lognormally distributed error, 221 for low doses and dose rates, 6, 181 in lung cancer risk estimates, 24~241, 270 model misspeeifieation, 165, 180, 223, 224 Monte Carlo analysis, 57, 168, 180 in mental retardation risks, 358 in neutron kerma, 222 non-model, 224 in point estimates of lifetime risk, 176-181
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From page 421... ...
INDEX in population effects, 218, 222, 223, 225, 241 procedures for addressing, 220-222 in radiation exposure data, 18, 19-20 in risk estimates, 57 from sampling variation, 6, 177-180, 217-218, 222 from sex differences, 219, 224-225 sources of, 3, 6, 57, 162 standard errors, 222, 237-238 statistical, 178-180 Underground miners, lung cancer in, 196, 239-241, 270-272 United Nations Scientific Committee on the Effects of Atomic Radiation (UNSCEAR) , 22, 65 calculation of genetic risk estimates in, 83 cancer risk model, 201 chromosome aberration risks, 83-84, 121-122 congenital abnormality frequencies, 92 extrapolation of animal data to humans, 67~8, 119 lifetime cancer risk estimates, 163, 174 lung cancer risk values, 271 measure of dominant lethals, 106-107 mutation rate estimation, 112 Uranium-234, 41 Uranium-235, 41 Uranium-238, 41 Uranium miners radionuclide effects in, 41, 272 skin cancer in, 326 Uranium workers carcinogenesis in, 138 radionuclide effects in, 41 Urinary tract cancer in A-bomb survivors, 318-319 in ankylosing spondylitis cohort, 319-320 in benign uterine bleeding cohort, 320 in cervical cancer patients, 320-321 in iodine-131 radiotherapy patients, 321 Uterine cancer, 314-315, 327-328 V Vitamins, 138 Von Hippel-Lindau syndrome, 92 421 W Water radiolysis, 1~15 Whelms' tumor, 35, 149 X X rays action producing biological damage, 20 animal studies of, 42, 81-82, 293, 294, 296, 298 chromosome aberrations from, 81-82, 84, 119-120, 121 correction to gamma rays, 82-83, 218 diagnostic, 19, 47 discovery and early studies of, 4~43 DNA chain breaks from, 37 dose-response relationships, 29, 37 microdosimetric spectra, 31 mutations in mice from, 101, 103, 104, 106 108, 110, 112, 114 from photoelectric process, 9 photon energies, 10 RBE of, 26, 29, 30, 82 soft, 21 spatial rate of energy loss, 11 Xeroderma pigmentosum, 35, 36, 37, 151 y Yeast, recombinational events in, 138 Yttrium-90, 42, 277 Yttrium-91, 42
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Key Terms
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