Induction of specific-locus and dominant lethal mutations in male mice in the low dose range by methyl methanesulfonate (MMS). 1990

U H Ehling, and A Neuhäuser-Klaus
GSF-Institut für Säugetiergenetik, Neuherberg, F.R.G.

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.

UI MeSH Term Description Entries
D008297 Male Males
D008741 Methyl Methanesulfonate An alkylating agent in cancer therapy that may also act as a mutagen by interfering with and causing damage to DNA. Methylmethane Sulfonate,Dimethylsulfonate,Mesilate, Methyl,Methyl Mesylate,Methyl Methylenesulfonate,Methylmesilate,Mesylate, Methyl,Methanesulfonate, Methyl,Methyl Mesilate
D009154 Mutation Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations. Mutations
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D005260 Female Females
D005799 Genes, Dominant Genes that influence the PHENOTYPE both in the homozygous and the heterozygous state. Conditions, Dominant Genetic,Dominant Genetic Conditions,Genetic Conditions, Dominant,Condition, Dominant Genetic,Dominant Gene,Dominant Genes,Dominant Genetic Condition,Gene, Dominant,Genetic Condition, Dominant
D005804 Genes, Lethal Genes whose loss of function or gain of function MUTATION leads to the death of the carrier prior to maturity. They may be essential genes (GENES, ESSENTIAL) required for viability, or genes which cause a block of function of an essential gene at a time when the essential gene function is required for viability. Alleles, Lethal,Allele, Lethal,Gene, Lethal,Lethal Allele,Lethal Alleles,Lethal Gene,Lethal Genes
D006720 Homozygote An individual in which both alleles at a given locus are identical. Homozygotes
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D013091 Spermatogenesis The process of germ cell development in the male from the primordial germ cells, through SPERMATOGONIA; SPERMATOCYTES; SPERMATIDS; to the mature haploid SPERMATOZOA. Spermatocytogenesis,Spermiogenesis

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