Metabolism of 2-acetylaminofluorene in cultured human lymphocytes.
The capacity of lymphocytes from 23 human subjects to metabolize the model carcinogen 2-acetylaminofluorene (AAF) was assessed. These cells metabolized AAF to its 1-, 7- and N-hydroxylated metabolites. Alpha-naphthoflavone and metyrapone exhibited IC50's for all pathways of 0.02 microM and 1 mM, respectively. These data indicate that the same form of cytochrome P450 or forms with similar IC50's are mediating these reactions. No significant difference was observed between lymphocytes from smokers versus non-smokers in the N-hydroxylation of AAF, the initial step in the metabolic activation of this carcinogen. However, lymphocytes from smokers were faster detoxifiers of AAF as seen in their increased capacity to 1- and 7-hydroxylate AAF compared to lymphocytes from non-smokers.
D015073:2-Acetylaminofluorene / Q000378:metabolism*; D001711:Biotransformation; D002478:Cells, Cultured; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D006801:Humans; D006881:Hydroxyacetylaminofluorene / Q000378:metabolism / Q000494:pharmacology; D008214:Lymphocytes / Q000201:enzymology / Q000378:metabolism*; D008797:Metyrapone / Q000494:pharmacology
D006881:Hydroxyacetylaminofluorene; D003577:Cytochrome P-450 Enzyme System; D015073:2-Acetylaminofluorene; D008797:Metyrapone