Add time:09/02/2019         Source:sciencedirect.com

Polybrominated biphenyls (PBBs) cause a mixed-type induction of liver microsomal drug-metabolizing enzymes. We have shown that 2,2′4,4′,5,5′-hexabromobiphenyl (HBB6), the major component (56%) of PBBs (Firemaster), is strictly a phenobarbital-type inducer, and are examining the effects of other purified PBB components on these hepatic enzymes Male rats were given one 90 mg/kg ip injection of either 2,2′-dibromobiphenyl (DBB) or of 2,2′,3,4,4′,5,5′-heptabromobiphenyl (HBB7), a major (27%) congener, and were sacrificed 1–22 days later. Eleven tissues were examined microscopically: Only HBB7 caused lesions which were confined to hepatocyte swelling and vacuolation. DBB had little if any effect on any parameter examined. In contrast, HBB7 increased liver weights and strongly induced microsomal protein, NADPH-cytochrome P-450 reductase, cytochrome P-450, aminopyrine demethylation, and epoxide hydratase. These effects were apparent within several days after treatment, and were still pronounced at Day 22. HBB7 caused only small increases in benzo[α]pyrene hydroxylation and p-nitrophenol-UDP-glucuronyltransferase and failed to shift the cytochrome P-450 spectral maximum from 450 nm. These results, and the results of sodium dodecylsulfatepolyacrylamide gel electrophoresis, indicate that HBB7, like HBB6, is strictly a phenobarbital-type inducer of hepatic microsomal drug-metabolizing enzymes, and that all brominated biphenyls are not inducers. Seventeen percent by weight of Firemaster remains uncharacterized; one or more of these components is responsible for the 3-methylcholanthrene-like aspects of the mixed-type induction caused by the PBB mixture.

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