Metabolism of 3,5,3',5'-tetrachlorobiphenyl by rat liver microsomes and purified P4501A1.
1. The metabolism of 3,5,3',5'-tetrachlorobiphenyl (TCB) was investigated with liver microsomes and purified P450 from the male Wistar rat. 2. One novel metabolite was produced after incubation with liver microsomes derived from the 3-methylcholanthrene (MC)- and 3,4,5,3',4'-pentachlorobiphenyl-pretreated rat, but not after incubation with those from the untreated or phenobarbital (PB)-pretreated rat. These results suggest that P450 isozyme(s) induced by MC-type inducers is involved in 3,5,3',5'-TCB metabolism. 3. The chemical structure of this metabolite was identified to be 4-hydroxy-3,5,3',5'-TCB by comparison of its retention time in glc and the ms with those of a synthetic sample. 4. Purified rat P4501A1, a major MC-inducible P450 isozyme, catalyzed the 4-hydroxylation of 3,5,3',5'-TCB, but P4502B1, a major PB-inducible isozyme, was inactive. 5. Reduced glutathione completely inhibited the formation of the hydroxylated metabolite, suggesting that 4-hydroxylation of 3,5,3',5'-TCB proceeded via the 3,4-epoxide.
Department of Food and Nutrition, Nakamura Gakuen University, Fukuoka, Japan.
N
N
Koga
N
N
Nishimura
H
H
Kuroki
Y
Y
Masuda
H
H
Yoshimura
D000818:Animals; D001711:Biotransformation; D002849:Chromatography, Gas; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D005978:Glutathione / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D013058:Mass Spectrometry; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism*; D011078:Polychlorinated Biphenyls / Q000493:pharmacokinetics*; D051381:Rats; D017208:Rats, Wistar; D012710:Serum Albumin, Bovine / Q000494:pharmacology
D012710:Serum Albumin, Bovine; D003577:Cytochrome P-450 Enzyme System; D011078:Polychlorinated Biphenyls; D005978:Glutathione; C029860:3,5,3',5'-tetrachlorobiphenyl