Interaction of bisphenol A with rat hepatic cytochrome P450 enzymes.
The effect of bisphenol A (BPA) on the kinetics of cytochrome P450 (P450)-dependent monooxygenases in rat liver microsomes was studied. Testosterone 16beta-hydroxylase (TS16BH) and testosterone 2alpha-hydroxylase (TS2AH) activities were extensively inhibited by BPA at 100 microM (69% and 74%, respectively). The inhibition type was mixed for both P450-dependent monooxyganases. The Ki of TS16BH and TS2AH from Lineweaver-Burk plots were 25.9 and 24.9 microM, respectively. The activities of acetanilide 4-hydroxylase (AA4H), 7-ethoxycoumarin O-deethylase (ECOD), bufuralol 1'-hydroxylase (BF1'H), chlorzoxazone 6-hydroxylase (CZ6H) and testosterone 6beta-hydroxylase (TS6BH) were also effectively inhibited by BPA at 100 microM (43-52%). The inhibition type of these P450-dependent monooxygenases was mixed or uncompetitive, and the K(i)s (50.5-88.5 microM) were higher than those of TS16BH and TS2AH. By contrast, the values of IC50 and Ki of testosterone 7alpha-hydroxylase (TS7AH) and lauric acid omega-hydroxylase (LAOH) for BPA were >1000 microM. These results suggest that BPA interacts with rat hepatic CYP1A2, CYP2A2, CYP2B2, CYP2C11, CYP2D1, CYP2E1 and CYP3A2 in vitro.
Hanioka
N
N
Division of Environmental Chemistry, National Institute of Health Sciences, Tokyo, Japan. hanioka@nihs.go.jp
Jinno
H
H
Tanaka-Kagawa
T
T
Nishimura
T
T
Ando
M
M
D000395:Air Pollutants, Occupational / Q000494:pharmacology*; D000818:Animals; D001559:Benzhydryl Compounds; D003577:Cytochrome P-450 Enzyme System / Q000187:drug effects / Q000378:metabolism*; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008297:Male; D008861:Microsomes / Q000187:drug effects / Q000201:enzymology; D010636:Phenols / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000098826:Bisphenol A Compounds
D000395:Air Pollutants, Occupational; D001559:Benzhydryl Compounds; D003577:Cytochrome P-450 Enzyme System; D010636:Phenols; C006780:bisphenol A; D000098826:Bisphenol A Compounds