Abstract
One of the major findings commonly observed in both A-bomb survivor studies and animal studies (and hence common underlying mechanisms are suspected to be involved) is higher risks of cancer when irradiated at younger ages. Several biologic mechanisms are possible; (1) Younger individuals may bear larger number of stem cells at risk (It suffices when we compare fetuses versus adults). (2) It may also be caused by larger number of stem cells that are actively cycling, which would cause higher rates of mutation induction (although it is not yet clearly known if non-dividing cells really show lower rate of mutation induction). (3) The number of target genes for mutagenesis may be larger in younger animals because only a few steps had passed and hence many genes can be candidates of mutagenesis, while adult or old individuals bear many mutations already and hence the number of candidate genes for mutagenesis would be limited. If we think of the mechanisms from epidemiologic stand point of view, somewhat different figures may be seen. Namely, (1) radiation exposure may add one step, only one step at most, toward carcinogenesis. Thus, a single exposure cannot induce a malignant transformation of normal cells. (2) The mean number of hits (mutations) accumulated in a target stem cell is quite small when young, and hence the same addition of one hit may give rise to larger effect when compared with the background rate (i.e., relative risk). (3) This idea leads us to a hypothesis that relative risk of cancer is expected to be lower for such people whose background rate is higher, which is in accord with the intuition that contribution of radiation would be smaller when contribution of genetic and environmental factors are larger. Vigorous tests of the hypothesis are needed.
