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Studies on chemically induced dominant lethality. II. Cytogenetic studies of MMS-induced dominant lethality in
Abstract:
Young adult female mice were injected intravenously with either 50- or 100- mg/kg doses of methyl methanesulfonate. The females were superovulated and mated to untreated males at intervals ranging from 0.5 to 14.5 days after treatment. The fertilized ova were collected and cultured to the first 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. This observation is consistent with the suggestion that an intervening round of DNA synthesis is 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 later spermatids and spermatozoa, are capable of performing macromolecular repair of premutational lesions.
Insights
Methyl methanesulfonate (MMS) causes low levels of chromosomal damage in female mouse oocytes, unlike in male germ cells. This suggests oocytes can repair MMS-induced DNA lesions before they cause mutations.
Area of Science:
- Toxicology
- Genetics
- Reproductive Biology
Background:
- Methyl methanesulfonate (MMS) is a known mutagen.
- Understanding the genotoxic effects of MMS on female germ cells is crucial for reproductive health.
- Previous studies indicated significant chromosomal damage in male germ cells exposed to MMS.
Purpose of the Study:
- To investigate the structural chromosomal damage induced by MMS in female mouse oocytes.
- To compare the sensitivity of female oocytes to MMS-induced damage with male germ cells.
- To explore the role of DNA repair mechanisms in oocytes following MMS exposure.
Main Methods:
- Young adult female mice received intravenous injections of methyl methanesulfonate (MMS) at 50 or 100 mg/kg.
- Superovulated females were mated at various intervals post-treatment (0.5–14.5 days).
- Fertilized ova were collected, cultured to first cleavage mitosis, and analyzed for chromosomal aberrations; metaphase I oocytes were also analyzed.
Main Results:
- Chromatid-type aberrations were observed in female oocytes, but at a significantly lower frequency compared to male germ cells.
- The timing and frequency of observed chromosomal damage correlated with existing dominant-lethal data for maturing oocytes.
- No significant MMS-induced chromosomal damage was detected in meiotic stage oocytes (metaphase I).
Conclusions:
- Maturing female oocytes exhibit a low yield of MMS-induced chromosomal damage.
- The lack of damage in meiotic stages suggests DNA synthesis is required for MMS lesions to manifest as aberrations.
- Female oocytes appear capable of repairing premutagenic MMS lesions, unlike later male germ cell stages.