Effects of 2,2′-Dibromobiphenyl and 2,2′,3,4,4′,5,5′-heptabromobiphenyl on liver microsomal drug metabolizing enzymes

Abstract

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 (HBB 6 ), 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 (HBB 7 ), a major (27%) congener, and were sacrificed 1–22 days later. Eleven tissues were examined microscopically: Only HBB 7 caused lesions which were confined to hepatocyte swelling and vacuolation. DBB had little if any effect on any parameter examined. In contrast, HBB 7 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. HBB 7 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 HBB 7 , like HBB 6 , 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.