STUDIES ON CHEMICALLY-INDUCED DOMINANT LETHALITY .2. CYTOGENETIC STUDIES OF MMS-INDUCED DOMINANT LETHALITY IN MATURING DICTYATE MOUSE OOCYTES

Young adult female mice were injected i.v. with either 50- or 100-mg/kg doses of methyl methanesulfonate [MMS]. The females were superovulated and mated to untreated males at intervals ranging from 0.5-14.5 days after treatment. The fertilized ova were collected and cultured to the 1st cleavage mitosis, at which time the female chromosome complement was analyzed for structural chromosomal damage. Chromatid-type aberrations were observed, but at a much lower frequency than previously reported for treatment of post-meiotic male germ cells. The time after treatment at which chromosomal damage was observed and the frequency of affected cells agree, qualitatively, with existing dominant-lethal data derived from treatment of maturing oocytes. Parallel experiments in which metaphase I oocytes were analyzed indicate a lack of MMS-induced chromosomal damage in the meiotic stages. An intervening round of DNA synthesis may be necessary for MMS-induced lesions to be translated into chromosomal damage. The low yield of chromosomal damage is consistent with the idea that maturing oocytes, unlike late spermatids and spermatozoa, are capable of performing macromolecular repair of premutational lesions.