First-generation litter-size reduction following irradiation of spermatogonial stem cells in mice and its use in risk estimation.

Litter-size reduction (LSR) is a useful measure of part of the overall F1 radiation-induced damage. Extensive LSR data were obtained as a by-product of specific-locus experiments. Fourteen such experiments involving 158,490 F1 litters have been analyzed for the extent of LSR induced by x- or gamma-irradiation of spermatogonia. Litter sizes were compared between experimental and control groups at about 3 weeks after birth. In order to reduce variability, comparisons were made only with concurrent controls and between groups of litters having mothers of approximately the same age. At the high dose rate of 90 R/min, the LSRs showed a humped dose-response curve. There was a pronounced dose-rate effect, the mutational responses being much less at dose rates of 0.009 R/min and 0.001 R/min. It is estimated that if men were exposed to 1 R of radiation delivered at low linear energy transfer (low LET) and low dose rate, the number of deaths caused by induced dominant mutations among their children before late childhood would be about 19 per million live-born. This can be added to the earlier estimate of an approximately equal number of viable disorders in all body systems as based on dominant skeletal mutations. This gives a total estimate of induced dominant damage, but much of this addition represents death in very early embryonic life that would not be recognized in humans. The LSR data also permit the conclusion that only an extremely small proportion of serious radiation-induced genetic disorders among live-born humans would be expected to result from segmental aneuploidy.