Stimulation of hepatic microsomal metabolism in mice by a mixture of polybrominated biphenyls

Abstract

The pattern of stimulation of hepatic microsomal mixed function oxidases has been studied in female NMRI mice following a single ip injection of 150 mg/kg polybrominated biphenyls (PBBs) and compared to the patterns produced by phenobarbital (PB), 3 × 100 mg/kg; 3‐methylcholanthrene (MC), 3 × 20 mg/kg; and these two agents administered together at these doses. Cytochrome P450, ethylmorphine N‐demethylase, and epoxide hydratase reached maximums of 200, 200, and 350% of control values, respectively, at 48 hr after treatment with PBBs. Ethoxycoumarin O‐deethylase and arylhydrocarbon hydroxylase were maximally increased to 400 and 180% of control values, respectively, 96 hr after PBBs. The reduced cytochrome P450 ethylisocyanide difference spectra and the inhibition of ethoxycoumarin O‐deethylase and arylhydrocarbon hydroxylase activity by metyrapone and α‐naphthoflavone indicated that the characteristics of the cytochrome P450 and the cytochrome P450‐dependent enzymes changed with time after administration of PBBs. These results indicate that the enzyme‐stimulating properties of PBBs alter, changing from PB‐like to MC‐like, with time after administration. These findings provide an explanation for the effects of PBBs on the toxicity of bromobenzene, indicating that PBBs represent a new and previously unrecognized class of toxicity‐modifying agents sharing properties of both PB and MC.