Clastogenic effects of benzo[a]pyrene in postimplantation embryos with different genetic background.

Abstract

Certain strains of mice vary in their enzyme inducibility by polycyclic hydrocarbons, i.e., the strain C57 shows high and the strain DBA shows low inducibility of aryl hydrocarbon hydroxylase (AHH) by benzo[a]pyrene (BaP). The effect of this genetically determined difference on the clastogenic response to BaP was studied in 11 day old embryos after transplacental treatment. The four possible crosses, C57 and DBA inter se, C57 X DBA and DBA X C57, were used to determine the influence of the genetic background on the aberration yields in the embryos. Constitutive and induced AHH levels were measured in liver, bone marrow, and placenta of the pregnant females and in their embryos. Enzyme inducibility was high in tissues of C57 dams and in their homozygous or heterozygous embryos. In contrast, induction of AHH activity was low in tissues of DBA females and their homozygous embryos. The high BaP-induced AHH activity found in heterozygous embryos of DBA dams is in agreement with the dominant mode of inheritance for high AHH inducibility. The cytogenetic results showed that the clastogenic response was lowest in homozygous C57 embryos and highest in hybrid embryos independent of the genetic constitution of the dams. Homozygous DBA embryos showed an intermediate aberration yield. The AHH inducibility by BaP did not correlate quantitatively with the induced aberration rates. However, the data suggest that BaP activation in embryonic tissue on day 11 of pregnancy is sufficient to account for the clastogenicity in the fetuses. It is concluded that the genetic endpoint chromosomal breakage is not only determined by the formation of active BaP metabolites but also by genetically controlled detoxification of BaP, repair process, and the rate of transformation of primary DNA lesions into true DNA discontinuities.