Strain differences in susceptibility to the embryotoxic effects of aminopyrine in mice

Embryotoxic effects induced by aminopyrine were studied in two inbred strains of mice, C57BL/6N and DBA/2N. Aminopyrine was given by subcutaneous injection at a dose of 200 mg/kg on day 7, 8 and 9 of gestation. In both strains, aminopyrine-induced malformations such as omphalocele, club foot and kinky tail were observed, but the incidence of malformations was significantly higher in C57BL/6N than in DBA/2N. Maternal plasma levels of aminopyrine and its metabolites were significantly higher in C57BL/6N, compared to DBA/2N. Further, reciprocal crosses between these two strains were used to clarify whether the maternal or fetal genotype is more important in aminopyrine-induced embryotoxicity. F1 hybrid embryos developing in C57BL/6N or DBA/2N mothers were as resistant as inbred DBA/2N. These results suggest that strain differences in susceptibility to aminopyrine may depend on fetal genotype rather than maternal factors.