[Metabolism of 2,2',5,5'-tetrachlorobiphenyl (CB52) by rabbit liver microsomes].
Our preceding studies have reported that 2,2',5,5'-tetrachlorobiphenyl (tetraCB)(CB52) is mainly metabolized to 3-hydroxy (OH)-metabolite by phenobarbital (PB)-inducible cytochrome P450 (P450) isoforms such as CYP2B1 and CYP2B18. In this study, the metabolism of CB52 by liver microsomes of untreated and PB-treated rabbits was investigated. Rabbit liver microsomes produced mainly 3-OH- and 4-OH-metabolites (M-1 and M-2) at an equal extent and two other metabolites (M-3 and M-4) and also that phenobarbital (PB) treatment accelerated the formation of all these metabolites, M-3 was assumed to OH-tetraCB by GC-MS. Another metabolite, M-4, was determined to 3,4-diOH-CB52 by GC-MS and 1H-NMR. Addition of antiserum against CYP2B4, a constitutive and PB-inducible rabbit P450 isoform, to a microsomal incubation system resulted in almost complete inhibition of the formation of 3-OH-, 4-OH- and 3,4-diOH-metabolites. These results suggest that CYP2B4 plays an important role in CB52 metabolism in rabbit liver.
Ohta
Chiho
C
Faculty of Nutritional Sciences, Nakamura Gakuen University, 5-7-1, Befu, Johnan-ku, Fukuoka 814-0198.
Haraguchi
Koichi
K
Kato
Yoshihisa
Y
Endo
Tetsuya
T
Koga
Nobuyuki
N
D000818:Animals; D007106:Immune Sera; D066298:In Vitro Techniques; D008297:Male; D008862:Microsomes, Liver / Q000276:immunology / Q000378:metabolism*; D011078:Polychlorinated Biphenyls / Q000378:metabolism*; D011817:Rabbits
D007106:Immune Sera; C009407:2,5,2',5'-tetrachlorobiphenyl; D011078:Polychlorinated Biphenyls