Metabolism of 2-aminofluorene and 2-acetylaminofluorene to mutagens by rat hepatocyte nuclei.

The Ames assay was used to determine the ability of rat hepatocyte nuclei to metabolize 2-aminofluorene (AF) and 2-acetylaminofluorene (AAF) to mutagens. When hepato cyte nuclei and hepatic postmitochondrial fraction (59) were compared, it was found that the distribution of these metabolic activities was unique for each fraction. Nuclei produced approximately 1260% more revertants with AF than with AAF, whereas S9 produced 1640% more mutants with AF than with AAF. Pretreatment with phenobarbital or methylcholanthrene, however, altered metabolic activity in a manner which was specifically unique for each fraction. Phenobarbital pretreatment increased nuclear activation of AF and AAF to mutagens by 400 and 460%, respectively. 59 from phenobarbital-treated rats showed a 57% increase in activation of AF, whereas AAF activation increased by 125%. Methylcholanthrene pretreatment increased nuclear activation of AF by 69%, whereas AAF activation increased by 375%. 59 activation of AAF was not altered by methyl cholanthrene pretreatment, but AF activation was increased by 41%. In a similar group of rats exposed to a carcinogenic regimen of AAF diet, nuclear activation of AF and AAF to mutagens was increased during the first month of feeding by 28 and 85%, respectively. However, after 16 weeks on the carcinogen regimen, nuclear activation of AF and AAF was reduced to 30 and 19% of control values, respectively. Thus, as has been demonstrated for other carcinogens, the hepatocyte nuclei are capable of activating aromatic amines to their mutagenic forms. The data suggest strongly that the metabolic pathways for the activation of AF and AAF differ and that AF may play a prominent role in mutagenesis.