Mechanisms of mutation induction in germ cells of the mouse as assessed bythe specific locus test

Mouse germ cell specific locus mutagenesis data and a molecular characteriz ation of mutant alleles have been reviewed to arrive at an understanding of the mechanism of mutation induction in mammals. (a) The spermatogenic stag e specificity for the sensitivity to mutation induction by 20 chemical muta gens is considered. (b) The effects of a saturable repair process and its r ecovery over time are examined for the mutagenic efficiency of ethylnitroso urea. (c) The mutagenic events following methylnitrosourea and chlorambucil are shown to be mainly deletions. in contrast the mutations recovered afte r ethylnitrosourea treatment are almost exclusively base pair substitutions . (d) It is emphasized that to date very few specific locus experiments hav e been designed to test for mutagenic events outside the interval stem cell spermatogonia-mature spermatozoa. A specific locus mutation has recently b een shown to be due to loss of heterozygosity via mitotic recombination in an early zygote stage and suggests a broader range of possible mechanisms o f mutation when these stages are considered. (e) With the cloning of all 7 marker loci mutation analysis at the molecular level will allow a more dire ct assessment of the mutation process in future studies. (C) 1999 Elsevier Science B.V. All rights reserved.