Microsomal metabolism of the carcinogen, N-2-fluorenylacetamide, by the mammary gland and liver of female rats. I. Ring- and N-hydroxylations of N-2-fluorenylacetamide

摘要: We determined ring- and N-hydroxylations of a systemic mammary gland carcinogen, N-2-fluorenylacetamide (2-FAA), by microsomal fractions liver female rats the effects in vivo and/or vitro modifiers these oxidations. Pretreatment lactating with 3-methylcholanthrene (3-MC) or beta-naphthoflavone (beta-NF) non-lactating (50-day old virgin) beta-NF showed similar that formation 3-, 5-, 7-, 9- N-hydroxy-2-FAA hepatic microsomes was increased manyfold 1-hydroxy-2-FAA induced. In microsomes, 5- 7-hydroxy-2-FAA likewise increased, but 9-hydroxy-2-FAA unaffected. Only had capacity for N-hydroxylation which approximately 3 times pretreatment 3-MC beta-NF. All induced increases metabolites 2-FAA were inhibited 0.1 mM alpha-naphthoflavone (alpha-NF) vitro. phenobarbital only further stimulated alpha-NF The latter also 7- hydroxy-2-FAA uninduced rats, no major metabolite. Hence, data qualitative quantitative differences between metabolism may result from levels (e.g., cytochrome P-450) activities enzymes herein. quantities (3-, N-hydroxy-2-FAA) found corn oil-treated only. solvent (methanol acetone) used addition to incubation mixtures altered quantitatively metabolite profiles treated rats. formations 1- 3- greater presence acetone methanol, respectively. results this study suggest phenolic N-hydroxy both is catalyzed form(s) P-450 beta-NF.(ABSTRACT TRUNCATED AT 400 WORDS)