Strain-dependent differences in the metabolism of 3-methylcholanthrene by maternal, placental, and fetal tissues of C57BL/6J and DBA/2J mice.
C57BL/6J (B6) and DBA/2J (D2) mice have different susceptibilities to developmental toxicity and transplacental carcinogenesis induced by in utero exposure to polycyclic aromatic hydrocarbons, which has been associated with polycyclic aromatic hydrocarbon metabolism and inducibility at the Ah locus. The distribution of total 3-methylcholanthrene (3-MC)-associated radioactivity in maternal, placental, and fetal tissues of beta-naphthoflavone-pretreated pregnant B6 and D2 mice was determined up to 12 h after p.o. exposure to [6-14C]-3-MC (63 mg/kg, 20 mu Ci) on gestational day 17. 3-MC-associated radioactivity in maternal plasma was not significantly different in the two strains. However, D2 tissue homogenates had consistently higher levels of 3-MC-associated radioactivity, which included both bound and free parent compound and metabolites. Increased metabolism of 3-MC by B6 maternal liver was suggested by the induced levels of aryl hydrocarbon hydroxylase activity in that tissue and by the observation that levels of total radioactivity decreased more rapidly in B6 tissues than in D2 tissues. The D2 fetal lung, the target tissue for 3-MC-induced transplacental carcinogenesis, appeared to accumulate 3-MC-associated radioactivity for a longer period of time than either the D2 fetal liver or the B6 fetal tissues. This study suggests that the genetic differences in fetal susceptibility to the developmental toxicity and transplacental carcinogenesis of 3-MC may be related to the presystemic elimination of the compound from both maternal and fetal tissues.
D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000378:metabolism; D001571:Benzoflavones / Q000494:pharmacology; D004790:Enzyme Induction / Q000187:drug effects; D005260:Female; D005333:Fetus / Q000378:metabolism*; D008099:Liver / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D008748:Methylcholanthrene / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL / Q000378:metabolism*; D008811:Mice, Inbred DBA / Q000378:metabolism*; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy; D013045:Species Specificity; D019324:beta-Naphthoflavone
D001571:Benzoflavones; D008748:Methylcholanthrene; D019324:beta-Naphthoflavone; D001189:Aryl Hydrocarbon Hydroxylases