The mutagenic effectiveness of fast neutrons in male and female mice

Abstract

Previous work has shown that protracted doses of fast neutrons induce high frequencies of specific locus mutations and of reciprocal translocations in mouse spermatogonia. However, they are mutagenically very ineffective when the dictyate oocyte is the stage at risk. The mutagenic response of similar germ-cell stages in the 2 sexes, namely the mitotically dividing primordial spermatogonia and oogonia with their precursors, has now been compared following irradiation for 1 week before the 12th day of embryonic life with a mean dose of 108.5 rad fast neutrons +20.5 R γ-contamination. The large clusters of specific locus mutations found in both series show conclusively t that mutations can be readily induced in female early embryonic germ cells as well as in male. Cluster size was used to estimate the mean number of germ cell at risk, from which mutation frequencies were calculated. These were 5.3·10 −5 per locus in males and 6.4·10 −5 per locus in females, from which induced mutation rates of 42·10 −8 and 58.10 −8 per rad respectively can be calculated. If dose attenuation is allowed for, higher figures are obtained. Those given are somewhat lower than the rate after protracted fast neutron irradiation of spermatogonia in the adult (109·10 −8 per rad) but higher than the mutation rates after low linear-energy transfer irradiation of spermatogonia and much higher than frequencies after protracted irradiation of dictyate oocytes. Air-dried preparations from testicular cell suspensions of 20 males irradiated as embryos were scored for presence of multivalent configurations indicating translocations. 2 had high and 2 had low frequencies of translocations; in addition, 1 mouse proved to be XYY and another had a clone of XO cells. The overall translocation frequency was 1.2%, which is lower than would be expected with irradiation of adult spermatogonia. It is concluded that the intrinsic radiosensitivity of male and female genetic material is similar in mice and that in the male these early embryonic stages are not much less sensitive than spermatogonia in the adult. It seems likely that the immature dictyate oocyte is the only germ-cell stage in the female from which mutations cannot be recovered.