FETAL TISSUES FROM VARIOUS STRAINS OF INDUCED MICE METABOLIZE BENZO(A)PYRENE TO MUTAGENIC METABOLITES

Since metabolic activation is known to mediate mutagenic and carcinogenic actions of certain chemicals, it is possible that embryopathic effects might also result from formation of reactive metabolites in fetal tissue. We evaluated this possibility by examining the activation of BaP 3 by fetal mouse liver homogenates ( + NADPH) to a mutagen(s) active in the “Salmonella‐microsome” assay. Three inbred mouse strains known to have high (B6), intermediate (C3H) and low (D2) inducibility of AHH and one random bred strain (CD1) were tested on gestational day 17, four days after an enzymeinducing dose of polychlorinated biphenyls. BaP induced TA1538 revertants in the presence of fetal liver homogenates from all strains with the order of activity being CD1 > B6 > C3H > D2. Although the number of revertants per mg fetal liver protein was only 5–10% of that found with maternal liver, it was linearly related to induced AHH activity measured by the fluorescence procedure. In contrast, the mutagenizing activity of placenta and whole fetus (minus liver) was lower than fetal liver and did not correlate with induced AHH activity. Activating potency did not correlate with either EH activity or the ratio of AHH/EH in maternal liver, fetal liver or placenta. These results support the postulated mechanism for embryopathic effects of chemicals that undergo metabolic activation to reactive metabolites and provide an explanation for genetically determined variation in response. Copyright © 1979 Wiley‐Liss, Inc., A Wiley Company