Polyhalogenated biphenyls and phenobarbital: Evaluation as inducers of drug metabolizing enzymes in the sheepshead, Archosargus probatocephalus

Abstract

Several doses of Aroclor 1254 (polychlorinated biphenyl (PCB) mixture), Firemaster FF1 (polybrominated biphenyl (PBB) mixture), 2,2′,4,4′,5,5′-hexabromobiphenyl (HBB), 3,3′,4,4′,5,5′-hexachlorobiphenyl (HCB) and phenobarbital (PB) were administered to the marine fish sheepshead ( Archosargus probatocephalus). The PCB and PBB mixtures caused induction of hepatic microsomal benzo[ a]pyrene hydroxylase (AHH), 7-ethoxycoumarin O-deethylase (7-EC) and 7-ethoxyresorufin O-deethylase (ERF) activities, but not benzphetamine N-demethylase (BND), epoxide hydrolase (EH) or glutathione S-transferase (GSH-T) activities. This induction pattern is typical of that caused by polycyclic aromatic hydrocarbons (PAH) in fish and mammals or by tetrachlorodibenzo- p-dioxin (TCDD) in mammals. The extent of induction of AHH-activity and cytochrome P-450 content was higher when experiments were carried out in summer (water temperature 25 ± 4°C) than in winter (water temperature 11 ± 3°C). Firemaster FF1 (15 mg/kg) induced fish for at least 56 days in both summer and winter at which time the liver concentrations of PBB were in the ppm range. PCB concentrations in the ppm range have been found in fish from polluted lakes and seas, thus we may expect that environmental exposure to PCB is sufficient to induce hepatic mixed function oxidase (MFO) activities. The PCB isomer 3,3′,4,4′,5,5′-HCB, which induces the same spectrum of hepatic drug-metabolizing activities as TCDD and PAH in rats, had a broadly similar effect in the sheepshead. Another purified isomer, 2,2′,4,4′,5,5′-HBB, which induces the same enzymes as PB in rats, had no effect on drug-metabolizing activities in sheepshead. PB was also without effect on sheepshead hepatic drug-metabolizing enzymes, although a typical narcotic effect was produced in PB-treated sheepshead. Our studies provide further evidence that drug-metabolizing activities in fish liver are readily induced by chemicals like TCDD or PAH, but we fail to demonstrate induction after treatment of sheepshead with inducers of the PB type.