MOLECULAR PHARMACOLOGY, 37:990-995 Involvement of Cytochrome P-450c in a-Naphthoflavone Metabolism by Rat Liver Microsomes

Metabolism of a-naphthoflavone (ANF) is increased markedly in rat liver microsomes by 3-methyicholanthrene (3-MG) and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), two inducers of cy-tochromes P-450c and P-450d (P-450c and P-450d). Although several indirect lines of evidence in the literature suggest that ANF is metabolized by P-450c, Vyas et a!. [J. Biol. Chem. 258:5649-5659 (1 983)] reported that ANF metabolism by 3-MG-induced rat liver microsomes was only partially inhibited by antibodies against P-450c. Our laboratory has previously re-ported clastogenic effects of metabolites of ANF, and in the present study we reexamined the role of P-450c in ANF metab-olism by both uninduced and TGDD-induced rat liver micro-somes, using monospecific polyclonal antibodies to P-450c and P-450d. ANF metabolism was inhibited to different extents in TGDD-induced microsomes by different preparations of anti-P