Expression of genetic damage induced by alkylating agents in germ cells of female mice.
The purpose of the present experiments was to analyse the frequencies of meiotic non-disjunction and structural aberrations by comparative cytogenetic investigations in unfertilized mII oocytes and first-cleavage metaphases after pre-ovulatory treatment of female mice with alkylating agents. We also present data on the expression of both types of aberration during embryogenesis in terms of dominant lethal effects. Trenimon (TR, 1 mg/kg) induced meiotic non-disjunction, but no structural aberrations were detected at metaphase II. On the contrary, at first-cleavage metaphase, TR revealed a strong clastogenic effect. A dose of 0.25 mg TR/kg increased the frequency of cells with structural aberrations to 51.79%. Mainly chromatid and a few isochromatid aberrations were found. These results support the observations previously made (see Brewen and Preston, 1979; Obe and Beek, 1979) that an intervening round of DNA replication is necessary for a TR-induced DNA lesion to be transformed into a structural aberration. The frequency of aberrant eggs in toto analysed at first cleavage (63.39%) can be quantitatively correlated to the rate of embryonic mortality (55.17%) as measured in the dominant lethal assay at the first day after treatment. We also present data on the effects of cyclophosphamide (CYC) on the first meiotic division. CYC (150 mg/kg) enhanced the incidence of meiotic non-disjunction only slightly, but induced a high frequency of dominant lethal effects (58.94%) at the first day after application.
D000477:Alkylating Agents / Q000494:pharmacology*; D000818:Animals; D002869:Chromosome Aberrations; D002875:Chromosomes / Q000187:drug effects*; D003520:Cyclophosphamide / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D005799:Genes, Dominant; D005804:Genes, Lethal; D008540:Meiosis / Q000187:drug effects; D051379:Mice; D009630:Nondisjunction, Genetic; D009865:Oocytes / Q000187:drug effects*; D010063:Ovum / Q000187:drug effects*; D010641:Phenotype
D000477:Alkylating Agents; D003520:Cyclophosphamide