Induction of xenobiotic metabolism in rat liver by chlorinated biphenyl ether isomers.
Chlorinated diphenyl ether isomers were administered to rats at doses of 10 mumols/kg/day po for 3 days. Decachlorodiphenyl ether caused increases in EPN detoxification, NADPH cytochrome c reductase and cytochrome P-450 but did not alter aryl hydrocarbon hydroxylase (AHH). It caused a shift in P450 absorption to 448 nm. 2,4,5,2',4'-Pentachlorodiphenyl ether increased EPN detoxification and cytochrome P-450. 2,4,5,3',4'-Pentachlorodiphenyl ether increased AHH and cytochrome P-450 and caused a shift in the absorption maximum to 448 nm. 3,4,2',4'-Tetrachlorodiphenyl ether induced AHH. 2,4'-Dichlorodiphenyl ether, 4,4'-dichlorodiphenyl ether, 2,4,2'-trichlorodiphenyl ether, 2,4,4'-trichlorodiphenyl ether, 3,4,2'-trichlorodiphenyl ether and 3,4,2',4'-tetrachlorodiphenyl ether did not alter any of these parameters. The position and degree of chlorination are important in determining the extent of induction and pathways induced.
D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000378:metabolism; D002713:Chlorine; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D008658:Inactivation, Metabolic; D007536:Isomerism; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009251:NADPH-Ferrihemoprotein Reductase / Q000378:metabolism; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D010647:Phenyl Ethers / Q000494:pharmacology*; D004849:Phenylphosphonothioic Acid, 2-Ethyl 2-(4-Nitrophenyl) Ester / Q000378:metabolism; D051381:Rats
D004364:Pharmaceutical Preparations; D010647:Phenyl Ethers; D004849:Phenylphosphonothioic Acid, 2-Ethyl 2-(4-Nitrophenyl) Ester; D002713:Chlorine; D003577:Cytochrome P-450 Enzyme System; D001189:Aryl Hydrocarbon Hydroxylases; D009251:NADPH-Ferrihemoprotein Reductase