Interaction of polycyclic aromatic hydrocarbons with human cytochrome P450 1B1 in inhibiting catalytic activity.

摘要: Eleven polycyclic aromatic hydrocarbons (PAHs) and 14 acetylenic PAHs biphenyls were used to analyze interactions with cytochrome P450 (P450) 1B1 in inhibiting catalytic activity, using 7-ethoxyresorufin O-deethylation (EROD) as a model reaction. Most of the chemicals examined direct inhibitors except for 4-(1-propynyl)biphenyl, mechanism-based inhibitor. In case inhibition EROD activity {15 24 chemicals, e.g., benzo[a]pyrene, 1-(1-propynyl)pyrene, 3-(1-propynyl)phenanthrene}, restoration occurred increasing incubation time, kinetic analysis showed that Km values higher these at initial stages but became lower time. With other nine 1B1-mediated increased during incubations. Acetylenic inhibitors, not 11 PAHs, induced reverse type I spectral changes 1B1, low dissociation constants (Ks) suggest...