Teratogenic interactions between methylmercury and mitomycin-C in mice

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.