TY - JOUR T1 - The Role of Cytochrome P-450 in <em>N</em>-Hydroxylaiton of 2-Acetylaminofluorene JF - Molecular Pharmacology JO - Mol Pharmacol SP - 398 LP - 404 VL - 9 IS - 3 AU - SNORRI S. THORGEIRSSON AU - DAVID J. JOLLOW AU - HENRY A. SASAME AU - IRA GREEN AU - JERRY R. MITCHELL Y1 - 1973/05/01 UR - http://molpharm.aspetjournals.org/content/9/3/398.abstract N2 - The role of cytochrome P-450 mixed-function oxidases in the N-oxidation of 2-acetylaminofluorene has been studied. N-Hydroxylation of 2-acetylaminofluorene in liver microsomes from mice or hamsters was inhibited by a carbon monoxide-oxygen (90:10) atmosphere. Prior treatment of mice with cobaltous chloride for 3 days decreased both the amount of cytochrome P-450 and the rate of N-hydroxylation of 2-acetylaminofluorene in liver microsomes by 55-60%. Immune serum and partially purified immunne γ-globulin against microsomal NADPH-cytochrome c reductase markedly inhibited both the N-hydroxylation of 2-acetylaminofluorene and N-demethylation of ethylmorphine in liver microsomes from hamsters. These results indicate that N-acetylarylamines can be N-oxidized by a cytochrome P-450-dependent mixed-function oxidase in liver microsomes. ACKNOWLEDGMENTS We are indebted to. Dr. J. R. Gillette, our laboratory chief, for invaluable help and advice during this study. We thank Dr. J. Weisburger, National Cancer Institute, for a generous gift of authentic N-hydroxy-2-acetylaminofluorene and for allowing us to see a preprint of his paper (5). ER -