Hamster liver cytochrome P450 (CYP2A8) as a 4-hydroxylase for 2,5,2',5'-tetrachlorobiphenyl.
Metabolism of 2,5,2',5'-tetrachlorobiphenyl (TCB) was studied using liver microsomes of hamsters and two hamster P450 isoforms, CYP1A2 and 2A8. CYP2A8 catalyzed selectively 4-hydroxylation of 2,5,2',5-TCB at a rate of 21.7 pmol/min/nmol P450. In contrast, CYP1A2 showed no activity for hydroxylation of 2,5,2',5'-TCB. Immunological study revealed that rabbit antiserum against CYP2A8 almost completely inhibited the microsomal 4-hydroxylation but that against CYP1A2 did not. It was also shown that the induction pattern of CYP2A8 protein by P450 inducer was similar to that of the 4-hydroxylase activity in hamster liver microsomes. These results suggest that CYP2A8 plays a major role in the 4-hydroxylation of 2,5,2',5'-TCB in hamster liver.
Koga
N
N
Department of Food and Nutrition, Nakamura Gakuen University, Fukuoka, Japan.
Kikuichi
N
N
Kanamaru
T
T
Ariyoshi
N
N
Oguri
K
K
Yoshimura
H
H
D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases; D015153:Blotting, Western; D002384:Catalysis; D006224:Cricetinae; D000072467:Cytochrome P450 Family 2; D007700:Kinetics; D008297:Male; D008647:Mesocricetus; D008862:Microsomes, Liver / Q000201:enzymology*; D006899:Mixed Function Oxygenases / Q000378:metabolism*; D011078:Polychlorinated Biphenyls / Q000378:metabolism*
C009407:2,5,2',5'-tetrachlorobiphenyl; D011078:Polychlorinated Biphenyls; D006899:Mixed Function Oxygenases; D001189:Aryl Hydrocarbon Hydroxylases; C101150:CYP2A8 protein, Mesocricetus auratus; D000072467:Cytochrome P450 Family 2