Reappraisal of studies concerning the genetic effects of the radiation of humans, mice, and Drosophila.

INTRODUCTION effort between U.S. and Japanese scientists have been summarized on a number of different occasions [cf. esp. Because of a number of recent developments, this Neel and Schull, 1991; Neel et al., 1997, in press] and I seems a propitious time to reassess the relative sensitivipropose to be extremely brief. Over the years, a cohort ties of humans, mice, and Drosophila to the genetic effects of 31,150 children born to parents receiving significant of ionizing radiation. As a population geneticist who is amounts of radiation (i.e., within 2 km of the bomb’s interested in the comparative sensitivity of various species hypocenter) and a somewhat larger control cohort to the genetic effects of ionizing radiation, I find these (41,066) have been studied with respect to a variety of effects best expressed in terms of ‘‘doubling dose,’’ deindicators: first, in the early years, for congenital defect, fined as the amount of gonadal exposure to ionizing radiasex of child, physical development, and survival, then, in tion that produces the same amount of mutation as occurs the middle years, for cytogenetic abnormality and, more spontaneously each generation in the population under recently, for the occurrence of malignant disease and for study. The concept is simple—deceptively simple, for, electrophoretic or functional defects in a battery of some as Muller [1959] pointed out many years ago, there are 30 serum proteins or erythrocyte enzymes. None of these numerous pitfalls in deriving this estimate and employing indicators was significantly related to parental radiation it in cross-species comparison. Ideally, as a population exposure but the net regression was slightly positive, but parameter it requires evaluating the sensitivity to radiation still nonsignificant. On the assumption that this small reof the various germ cell stages throughout the prereprogression term was a radiation effect, and that we could ductive and reproductive portion of the organism’s life estimate the contribution that spontaneous mutation cycle. Unfortunately, the chief alternative to deriving a makes each generation to the previously mentioned indidoubling dose, namely, expressing effects simply as excators, our estimate of the zygotic doubling dose was in cess probability of mutations per locus per Gy for a chothe neighborhood of 2 Sv equivalents. There is a large sen battery of genes radiated at a specific time in the life but indeterminate error attached to this estimate, but we cycle, leaves one with little perspective in risk setting. suggested the lower (95%) boundary might be 1 Sv equivOtherwise stated, the rate per locus in a specific sex at a alent, whereas the upper boundary is indeterminate. We specific point in the life cycle is an interesting laboratory believe that in reaching this estimate our genetic assumpparameter but the doubling dose is an absolutely basic tions regarding the impact of mutation in the preceding parameter in evolutionary and population genetics, not to generation were quite conservative; in addition, we are mention risk setting, which, not surprisingly, is much keenly aware that the somewhat lower socioeconomic more difficult to evaluate. Although in most experimental status of the exposed parents in the decade following the studies the results are expressed in terms of gametic douwar could have contributed to the frequency of early death bling dose, in the studies in Japan we are concerned with in their children [Kato et al., 1966], and so biased downthe results of exposure of one or both parents, and risk is best expressed in terms of zygotic doubling dose.