Influence of chlordecone and mirex exposure on benzo[a]pyrene metabolism of rat-liver microsomes.
The metabolism of benzo[a]pyrene (BP) in hepatic microsomes isolated from rats exposed to chlordecone or mirex was compared to that of untreated rats and rats treated with 3-methylcholanthrene (3-MC) or phenobarbital (PB). Treatment with chlordecone resulted in a two- to three-fold increase in cytochrome P-450 content but the BP-hydroxylase activity per mg microsomal protein was unaffected. Addition of alpha-naphthoflavone (alpha-NF) or chlordecone caused changes in BP-hydroxylase activity indicating that chlordecone-induced cytochromes P-450 were similar to control. H.p.l.c. analyses of BP metabolites confirmed this similarity. Treatment with mirex caused a two-fold induction of cytochrome P-450, and BP-hydroxylase activity expressed per mg microsomal protein was increased 1.3-fold. Addition of chlordecone or alpha-NF caused changes in BP-hydroxylase activity, indicating differences between control and mirex-induced cytochromes P-450. H.p.l.c. analyses of BP metabolites confirmed this difference. Treatment with chlordecone or mirex increased microsomal epoxide hydrolase activity three-fold. Chlordecone accumulated in hepatic nuclei.
D000818:Animals; D001564:Benzo(a)pyrene / Q000378:metabolism*; D001571:Benzoflavones / Q000494:pharmacology; D001711:Biotransformation / Q000187:drug effects; D007631:Chlordecone / Q000494:pharmacology*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004851:Epoxide Hydrolases / Q000378:metabolism; D007306:Insecticides / Q000494:pharmacology*; D008099:Liver / Q000378:metabolism; D008748:Methylcholanthrene / Q000494:pharmacology; D008862:Microsomes, Liver / Q000378:metabolism*; D008917:Mirex / Q000494:pharmacology*; D010573:Pesticide Residues / Q000378:metabolism; D010634:Phenobarbital / Q000494:pharmacology; D051381:Rats; D013347:Subcellular Fractions / Q000378:metabolism
D001571:Benzoflavones; D007306:Insecticides; D010573:Pesticide Residues; D001564:Benzo(a)pyrene; D008748:Methylcholanthrene; C011512:alpha-naphthoflavone; D003577:Cytochrome P-450 Enzyme System; D004851:Epoxide Hydrolases; D007631:Chlordecone; D010634:Phenobarbital; D008917:Mirex