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RESEARCH PRODUCT

The induction of hepatic microsomal metabolism in rats following acute administration of a mixture of polybrominated biphenyls.

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Abstract Firemaster BP6, a mixture of polybrominated biphenyls (PBBs), was administered to female Sprague-Dawley rats (170–180 g) as a single ip injection at 25 and 150 mg/kg. Other animals received phenobarbital (PB), 3-methylcholanthrene (3MC), or PB and 3MC together. Animals were killed at intervals of 12, 24, 48, 192, and 336 hr after treatment with PBBs, or 24 hr after PB, MC, or PB-MC, and various hepatic microsomal parameters were measured. After 150 mg/kg of PBBs, cytochrome P450 concentrations reached a maximum by 48 hr (225% of control), then remained elevated through 336 hr. A similar pattern of induction was observed for epoxide hydratase and aniline hydroxylase activities. In contrast, ethylmorphine- N -demethylase and ethoxycoumarin- O -deethylase activities initially increased to 256 and 1379% of control, respectively, at 48 hr, then continued to increase to 583 and 3197% of control at 336 hr. Ethylmorphine- N -demethylase was induced by PB (579% of control) but not 3MC, and ethoxycoumarin- O -deethylase was more sensitive to 3MC (3852% of control) than PB (891% of control). Arylhydrocarbon hydroxylase activity was 1531% of control 192 hr after 150 mg/kg of PBBs which was similar to the activity induced by PB-3MC (1851% of control) but less than that induced by 3MC alone (3499% of control). No significant increases were observed in any parameters until 192 hr after treatment with 25 mg/kg of PBBs. The enzyme activities and the wavelength of maximum absorption for the cytochrome P450-CO complex from microsomes of animals treated with PBBs indicated that the PBBs produced a “mixed” type of hepatic microsomal enzyme induction with inducing properties of both PB and 3MC.