Adverse Reproductive Outcomes in Families of Atomic Veterans The Feasibility of Epidemiologic Studies (1995) / Chapter Skim
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6. CURRENT KNOWLEDGE AND ESTIMATION OF GENETIC RISK
6. CURRENT KNOWLEDGE AND ESTIMATION OF GENETIC RISK
Pages 29-41
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From page 29... ...
In what follows it is important to understand three points: 1. The health effects resulting from mutations induced by ionizing radiation are indistinguishable from those resulting from other agents or that arise spontaneously.
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From page 30... ...
of genetic effects due to radiation, often called the induced burden, S is the number of cases (per generation) normally present in a population not exposed to additional radiation, the spontaneous burden, DD is the doubling dose (see below)
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From page 31... ...
If the dose-response curve is not linear but concave upward, this use of the doubling dose in Equation 1 will tend to overestimate risk if the data from which doubling dose is estimated are obtained from high doses. The doubling dose has traditionally been estimated from experimental animal data, mostly the mouse, although an estimate is also provided by the extensive studies of the children of atomic bomb survivors from Hiroshima and Nagasaki.
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From page 32... ...
For example, the dominant cataract mutation frequency in the mouse was estimated to be 0.15-0.18 x 10-6 mutations per 0.01 Gy per gamete for low dose rate data. It was also estimated that approximately 2.7% of all serious dominant mutations are cataract causing mutations, i.e., M = 36.8.
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From page 33... ...
The mouse is the only mammal for which substantial data on the mutagenic effects of ionizing radiation are available. These effects have been shown to depend on dose, dose rate, fractionation pattern, LET, cell stage, sex, age at exposure, and the test stock and gene loci used.
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From page 34... ...
The major studies that have provided estimates of the spontaneous burden for a number of genetic categories are provided elsewhere (Stevenson, 1959; Trimble and Doughty, 1974; Jacobs, 1975; Carr and Gedeon, 1977; Carter, 1977; Hook and Hamerton, 1977; Childs, 1981; Czeizel and Sankaranarayanan, 1984~. A summary of findings is provided in Table 1 (Table 2-5 of BEIR [NRC, 1990]
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From page 35... ...
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From page 36... ...
Estimating the Effect of Ionizing Radiation The cohort of atomic bomb survivors and their children from Hiroshima and Nagasaki is the main body of humans capable of providing estimates of the effects of ionizing radiation on the incidence of genetic disorders. In November 1946, a presidential directive was issued at the request of the Secretary of the Navy, James T
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From page 37... ...
Overall, the studies of health outcomes in the Hiroshima-Nagasaki atomic bomb survivors and their children have revealed a small but statistically nonsignificant difference in health outcomes between the children of the atomic bomb survivors conceived subsequent to the bombing and the children of nonexposed
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From page 38... ...
ionizing radiation for a number of different endpoints. The ranges in parentheses were obtained by the BEIR V committee by multiplying acute doubling dose estimates by a correction factor range of 5-10.
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From page 39... ...
Genetic Endpoint and Sex Doubling Dose (rads) a Dominant lethal mutations, Both sexes Recessive lethal mutations, Both sexes Dominant visible mutations Male Skeletal Cataract Other Female Recessive visible mutations Postgonial, male Postgonial, female Gonial, male Reciprocal translocations Male Mouse Rhesus monkey Heritable translocations Male Female Congenital malformations Female, postgonial Male, postgonial Male, genial Aneuploidy (hyperhaploids)
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From page 40... ...
have recently attempted to resolve this difference by suggesting that, overall, the mouse estimates of doubling doses are actually higher than those suggested in Table 2. In sum, the general scientific consensus is that the overall doubling dose of mutation induction for low-LET, low-dose ionizing radiation is on the order of 100 rem, and it may, in fact, be larger.
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From page 41... ...
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