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Micronucleus induction in mouse and rat fetuses treated transplacentally during histogenesis with mitomycin C and
1Institute for Drugs, Federal Health Office, Berlin, Federal Republic of Germany.
Abstract:
During histogenesis, mouse and rat fetuses were treated transplacentally with mitomycin C (MMC) and 7,12-dimethylbenz(a)anthracene (DMBA). The micronucleus (MN)-inducing effects of MMC were analysed in mouse fetal blood and liver; the effects of DMBA were analysed in mouse fetal and rat fetal blood and in maternal bone marrow of both species. Both test substances were clearly clastogenic during the period of development in which the embryos were analysed--i.e., MMC from gestational day 14 until day 18 in mice and DMBA on days 14 and 17 in mice and days 16 and 19 in rats. In mouse fetal liver and blood the MMC-induced MN frequencies did not vary significantly during the whole period. MMC was more effective in fetal blood than in fetal liver. DMBA-induced MN frequencies in maternal bone marrow were slightly higher in rats than in mice. Compared to maternal bone marrow, fetal MN frequencies were about four to five times higher in rats but less than two times higher in mice. Thus, rat fetuses were far more susceptible to the clastogenic action of DMBA than mouse fetuses. These results are discussed with respect to fetal development and maternal/fetal metabolism.
Insights
Rat fetuses showed higher susceptibility to the clastogenic effects of 7,12-dimethylbenz(a)anthracene (DMBA) than mouse fetuses. Mitomycin C (MMC) was more effective in fetal blood than liver in mice.
Area of Science:
- Developmental toxicology
- Genotoxicity testing
- Comparative toxicology
Background:
- Transplacental exposure during histogenesis is critical for fetal development.
- Mitomycin C (MMC) and 7,12-dimethylbenz(a)anthracene (DMBA) are known clastogens.
- Assessing fetal susceptibility to genotoxic agents is crucial for risk evaluation.
Purpose of the Study:
- To compare the clastogenic effects of MMC and DMBA in mouse and rat fetuses during histogenesis.
- To evaluate the influence of maternal and fetal metabolism on genotoxicity.
- To determine species-specific susceptibility to transplacentally administered genotoxic agents.
Main Methods:
- Transplacental administration of MMC and DMBA to pregnant mice and rats during critical developmental periods.
- Micronucleus (MN) assay in fetal blood, fetal liver, and maternal bone marrow.
- Analysis of MN frequencies to assess clastogenic activity.
Main Results:
- Both MMC and DMBA demonstrated clear clastogenic effects during embryonic development.
- MMC was more effective in inducing micronuclei in mouse fetal blood compared to fetal liver.
- Rat fetuses exhibited significantly higher susceptibility to DMBA-induced clastogenicity than mouse fetuses, with MN frequencies 4-5 times higher in fetal blood compared to maternal bone marrow.
Conclusions:
- Fetal susceptibility to DMBA's clastogenic action varies significantly between rats and mice.
- Maternal and fetal metabolism likely play a role in differential susceptibility to genotoxic agents.
- The study highlights the importance of species-specific risk assessment for developmental exposure to genotoxins.