Sterile period, translocation and specific locus mutation in the mouse following fractionated x-ray treatments with different fractionation intervals

Abstract

The genetic response of the mouse spermatogonial stem cell to high doses of X-rays given in two fractions is dependent upon the fractionation interval. When 800 R was administered in two fractions, 500 plus 300 R, separated by intervals varying from 24 h to 12 days, the recovered translocation yield was consistent with addivity. However, with intervals of 3 to 12 days, the response was less than additive and was closer to that of the single 800 R dose. When 1000 R was administered in two fractions of 500 R separated by intervals of 4 days and 7 days, the recovered yield of specific locus mutations approximated the additive levels. There was no enhancement of the response, as obtained with 24-h fractionation. In neither experiment was there an indication of any kind of correlation with stem cell killing, as indicated by length of sterile period. It is proposed that the results could be interpreted on the assumption of a spermatogonial stem cell having a long cell cycle (several days) such that in the first two days following one radiation exposure the surviving cells are particularly sensitive to the induction of both gene mutations and translocations by a second treatment. It is further suggested that the relative response of gene mutation and translocation to fractionated treatments is essentially the same but approximately half of those cells carrying translocations are eliminated by selection.