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 hydrolyase activity three-fold. Chlordecone accumulated in hepatic nuclei.