Induction of specific-locus and dominant lethal mutations in male mice by 1-methyl-1-nitrosourea (MNU).

1-Methyl-1-nitrosourea (MNU) induced specific-locus mutations in mice in all spermatogenic stages except spermatozoa. After intraperitoneal injection of 70 mg/kg body weight of MNU a high yield of specific-locus mutations was observed in spermatids (21.8 x 10(-5) mutations per locus per gamete). The highest mutational yield was induced in differentiating spermatogonia. In 1594 offspring we observed 5 specific-locus mutants (44.8 x 10(-5) mutations per locus per gamete). In addition, 2 mosaics were recovered, which gave a combined mutation rate of 62.7 x 10(-5). In As spermatogonia the mutation rate was 3.9 x 10(-5). The same dose of 70 mg/kg of MNU induced dominant lethal mutations 5-48 days post treatment, mainly due to post-implantation loss in spermatids and spermatocytes. It is interesting to compare the induction pattern of mutations by MNU with methyl methanesulfonate (MMS), ethyl methanesulfonate (EMS) and ethylnitrosourea (ENU). Based on the different spermatogenic response of the induction of specific-locus mutations we can characterize the 4 mutagens in the following way: EMS = MMS not equal to MNU not equal to ENU.