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Molecular Pharmacology, Vol 9, 398-404, Copyright © 1973 by the American Society for Pharmacology and Experimental Therapeutics

The Role of Cytochrome P-450 in N-Hydroxylaiton of 2-Acetylaminofluorene

SNORRI S. THORGEIRSSON 1, DAVID J. JOLLOW 1, HENRY A. SASAME 1, IRA GREEN 1, and JERRY R. MITCHELL 1

1 Laboratory of Chemical Pharmacology, National Heart and Lung Institute, and Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland 20014

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 ggr-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.

Note:
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).

Submitted on November 20, 1972




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