title: Induction of specific-locus and dominant lethal mutations in male mice in the low dose range by methyl methanesulfonate (MMS).
abstract: Methyl methanesulfonate (MMS) induces specific-locus and dominant lethal mutations in spermatozoa and spermatids of mice. A dose of 15 mg/kg b.w. of MMS induces 9% dominant lethal mutations in the most sensitive germ-cell stages, corresponding to the mating intervals 5-8 and 9-12 days post treatment. A dose of 150 mg/kg b.w. of MMS in the same mating intervals induces 100% dominant lethal mutations. The sensitivity pattern for the induction of dominant lethal and specific-locus mutations is the same. In the mating interval 5-8 days a dose of 20 mg/kg b.w. of MMS induced 3.8 x 10(-5) mutations per locus per gamete. The yield of specific-locus and dominant lethal mutations in the low dose range increases proportionally with the dose. A dose given in 2, 4 or 5 fractions yields the same frequency of mutations as a single injection of the total dose. The additivity of small doses proves that the pre-mutational lesions are not or only partially repaired in these stages and that MMS is not or only partially detoxified. In addition, the frequency of dominant lethal and specific-locus mutations depends on the germ-cell stage.
authors.affiliation: GSF-Institut für Säugetiergenetik, Neuherberg, F.R.G.
authors.forename: U H
authors.initials: UH
authors.lastname: Ehling
authors.forename: A
authors.initials: A
authors.lastname: Neuhäuser-Klaus
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D005260:Female; D005799:Genes, Dominant; D005804:Genes, Lethal; D006720:Homozygote; D008297:Male; D008741:Methyl Methanesulfonate / Q000633:toxicity*; D051379:Mice; D009154:Mutation; D013091:Spermatogenesis; D013094:Spermatozoa / Q000187:drug effects*; D013997:Time Factors
chemical_list: D008741:Methyl Methanesulfonate