Effects of Antimutagens on the Teratogenicity of N-Methyl-N'-Nitro-N-Nitrosoguanidine in Mice.

We examined whether vanillin (VA) and CoCl ∙6H O(CoCl ), antimutagens, which have mutation suppressing effect, i.e., promotion of cellular repair function in vitro, can modify the teratogenicity in mice caused by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), a direct-acting monofunctional alkylating agent. ICR mice were treated with MNNG alone (single IP dose of 40 or 60 mg/kg) or in combination with the antimutagen on day 11 of gestation. Embryotoxicity and teratogenicity were examined at term. The incidence of MNNG-induced syndactyly in the fore- and hindlimbs was significantly decreased by VA (50 mg/kg, IP) or CoCl (10 mg/kg, IV) and a tendency to decrease in the incidence of oligodactyly was noted as well. On the other hand, the incidence of MNNG-induced brachydactyly was increased by VA or CoCl . Though the mechanism of the modifying effects of both VA and CoCl on MNNG-induced malformations could not be delineated in the present study, the results indicate that the antimutagens which stimulate DNA recombination repair in vitro modify the manifestation of malformations caused by teratogens that attack the fetal DNA in the initial teratogenic mechanism.