The great majority of data on the assessment of genetic or heritable effects in human populations following exposure to radiation has come from studies of the atomic bomb survivors. The following end points have been assessed: untoward pregnancy outcomes (major congenital malformation, stillbirth, neonatal death); sex of child; tumors with onset prior to the age of 20; death of liveborn infants through an average age of 26.2 years, exclusive of death from malignancy; growth and development of liveborn infants; cytogenetic abnormalities; and mutations altering the electrophoretic behavior or function of a selected battery of erythrocyte and blood plasma proteins. There were no significant increases in any of these indicators from a combined parental gonadal equivalent dose of 0.4 to 0.5 Sv.73
A recent study by Kodaira et al. examined variations in size of six minisatellite regions (see glossary) in the DNA of 64 children from 50 families in which one or both parents were exposed to the atomic bomb explosion and in 60 children from families in which neither parent was exposed.74 There was no difference in the frequency of change in the two groups. A similar result was reported by Satoh et al. for mutations detected by the denaturing gradient-gel electrophoretic method.75
UNSCEAR76 made estimates of the (unirradiated) background incidence of mutational effects per generation for the end points studied on the acutely exposed Japanese population. The values ranged from approximately 10-5 per locus for loci encoding proteins to 3 × 10-3 per locus for untoward pregnancy outcomes. UNSCEAR also estimated the acute dose that would, on average, double the background incidence—the doubling dose—as 1.7 to 2.2 Sv. Allowing for chronic exposure, a gonadal dose reduction factor was applied to give a minimal estimated doubling dose of 4 Sv for genetic effects. A complete description of the approach used may be found in UNSCEAR77 and in Neel and Schull.78 The present lifetime exposure limit for astronauts is < 4 Sv. Hence the actual increase above background in heritable effects per locus, depending on the particular locus, and the risk of heritable effects to individuals engaged in extended space travel will be low. In addition, because the number of individuals who might be exposed to ionizing radiation during long-range spaceflight will represent a very small fraction of the population, any genetic risk to the human gene pool would be negligible.
The rapid increase in knowledge of the mechanisms of tumor induction and heritable effects has led to a clear appreciation of the potential for a genetic predisposition to the induction of cancer by exogenous agents and endogenous processes and to induction of heritable changes. Such a predisposition might be specific for a single agent such as ionizing radiation (e.g., predisposition in ataxia telangiectasia heterozygotes) or it might involve sensitivity to a wide range of exogenous agents and endogenous processes (e.g., Li-Fraumeni syndrome (p53 heterozygosity)). Given that within the normal human population a range of risk exists for induction of cancer, it is difficult at this time to assign a value for increased risk owing to a single genetic susceptibility. In general, most of the genetic susceptibility or sensitivity factors that are common in the population tend to increase relative risk by small amounts. Those conferring high relative risk are present at a low frequency. The latter is particularly true for susceptibility for which background frequencies of cancer are high.
It has become increasingly apparent that the sensitivity of cells to radiation is controlled in part by the relationship of DNA repair kinetics to cell cycle progression. The quintessential example is the gene p53, which is involved in cell cycle control at the G1 checkpoint, the time point in the cell cycle at which DNA synthesis begins, and in the repair of DNA damage either directly or indirectly.79 A deficiency in p53 can both affect the efficiency of DNA repair and abrogate the G1 checkpoint, both of which can increase sensitivity to the induction of mutations and chromosomal aberrations. At G2, which is the time between the end of DNA synthesis and mitosis (the G2/M checkpoint), p53 appears to function in the direct repair of DNA damage, and not in control at the G2/M checkpoint.80 Mice that are homozygous or heterozygous for a knockout of the p53 gene are more susceptible to both spontaneous tumor formation, and tumor formation following exposure to a range of chemicals.81