Experimental model for evaluating the effects of genetic and exogenous factors on transplacental mutagenesis

Cyclophosphamide (CP)-induced micronuclei were evaluated in females of two strains of mice (C57BL and CD1), in F1 hybrid females and in fetuses (day 13 of gestation) obtained from different crosses. F1 adult hybrids from a cross between the strain with a high level of induced micronuclei (C57BL) and the strain with a low response (CD1) exhibited micronuclei values closer to the latter. CD1/CD1 fetuses showed a higher susceptibility than C57BL/C57BL ones. Heterozygous fetuses from reciprocal crosses, whatever the maternal genotype, showed the same sensitivity, which is very close to that of C57BL/C57BL fetuses. Phenobarbital (PB) pre-treatment modified the mutagenic response to CP depending on the genotype of the treated animal. These results demonstrate that the response to a pro-mutagen requiring metabolic activation depends to a large extent on the genetic background of the target animals, and that mother-fetus interactions in transplacental mutagenesis seem to depend more on the fetal than on the maternal genotype.