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Teratogenic interactions between methylmercury and mitomycin-C in mice
1National Institute for Minamata Disease, Kumamoto, Japan.
Abstract:
Pregnant mice were given p.o. various nonteratogenic doses (0, 2.5, 5 and 10 mg/kg) of methylmercuric chloride on day 9 of pregnancy, and then injected i.p. with a teratogenic dose (4 mg/kg) of mitomycin-C on day 10. Major malformations produced by mitomycin-C alone were cervical rib and vertebral anomaly, polydactyly of the hindlimb and tail anomaly. Combined treatment significantly increased the incidence of these malformations, showing the dose-effect relationship of methylmercury, whereas methylmercury alone is known not to produce such malformations. When mitomycin-C treatment alone was performed on day 9.5 of pregnancy, only vertebral anomalies increased in incidence. Therefore, mitomycin-C teratogenicity in terms of the manifestation of cervical rib, polydactyly and tail anomaly, but not vertebral anomaly, was suggested to be enhanced by methylmercury. A considerable number of foetuses showed cleft palate involvement following combined treatments, but not by either chemical alone. Cleft palate is known to be a major malformation in mice that is caused by methylmercury, and mitomycin-C also induces cleft palate. Therefore, the two chemicals might have affected foetuses additively and thereby induced cleft palate.
Insights
Methylmercuric chloride exposure during pregnancy enhanced mitomycin-C
Area of Science:
- Toxicology
- Developmental Biology
- Teratology
Background:
- Methylmercury is a known teratogen, causing major malformations in developing fetuses.
- Mitomycin-C is a chemotherapeutic agent with teratogenic potential.
- Understanding combined exposure effects is crucial for risk assessment.
Purpose of the Study:
- To investigate the combined teratogenic effects of methylmercuric chloride and mitomycin-C in pregnant mice.
- To determine if methylmercury enhances mitomycin-C-induced malformations.
- To assess the additive effects on cleft palate formation.
Main Methods:
- Pregnant mice were administered varying doses of methylmercuric chloride orally on day 9 of gestation.
- A teratogenic dose of mitomycin-C was administered intraperitoneally on day 10.
- Fetal examination for major malformations, including cervical rib, vertebral anomalies, polydactyly, tail anomalies, and cleft palate.
Main Results:
- Combined treatment significantly increased the incidence of cervical rib, hindlimb polydactyly, and tail anomalies compared to mitomycin-C alone.
- Methylmercury demonstrated a dose-dependent enhancement of these specific mitomycin-C-induced malformations.
- A notable increase in cleft palate was observed with combined exposure, suggesting additive effects.
Conclusions:
- Methylmercury exposure potentiates mitomycin-C teratogenicity for specific malformations (cervical rib, polydactyly, tail anomaly) but not vertebral anomalies.
- The combined exposure of methylmercury and mitomycin-C leads to an additive effect in inducing cleft palate in mouse fetuses.
- These findings highlight the complex interactions between environmental toxins and chemotherapeutic agents during pregnancy.