Stimulation of hepatic microsomal metabolism in mice by a mixture of polybrominated biphenyls.
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 X 100 mg/kg; 3-methylcholanthrene (MC), 3 X 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 alpha-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 calss of toxicity-modifying agents sharing properties of both PB and MC.
D000818:Animals; D000963:Antimetabolites; D001713:Biphenyl Compounds / Q000494:pharmacology*; D001835:Body Weight / Q000187:drug effects; D003486:Cyanides; D005019:Ethyl Ethers / Q000494:pharmacology; D005260:Female; D051379:Mice; D008862:Microsomes, Liver / Q000201:enzymology / Q000378:metabolism*; D009929:Organ Size / Q000187:drug effects; D011075:Polybrominated Biphenyls / Q000494:pharmacology*; D013268:Stimulation, Chemical; D013997:Time Factors
D000963:Antimetabolites; D001713:Biphenyl Compounds; D003486:Cyanides; D005019:Ethyl Ethers; D011075:Polybrominated Biphenyls