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.