The Metabolism of 2-Aminofluorene in the Rat*

The study of the metabolism of 2-aminofluorene (AF) has become of considerable importance, since it has been demonstrated that 2-acetylaminofluorene (AAF) is rapidly deacetylated in the rat (8, 13). This observation indicates that AF is a major product in the degradation of AAF by the rat and that the metabolism of AAF may be iden tical with that of AF. The metabolism of AF is also of interest from another point of view. AAF, which is readily hydrolyzed by the rat to AF, is a powerful carcinogenic agent. On the other hand, 2-benzoylaminofluorenel and 2-p-toluenesulfonamidofluorene, which are more resistant to hydrol ysis in vivo (12), have proved to be either weakly carcinogenic or not carcinogenic.2 These findings suggest that the free amino group may be re quired for the carcinogenic action of this class of amines. The metabolism of AF has been previously in vestigated in the rabbit by Westfall (14). The quantity of acetone-extractable, diazotizable ma terial in various tissues was estimated 18 hours following the subcutaneous administration of the compound. Only small amounts of nitrogen-con jugated compound were found after hydrolysis of the extracts with hydrochloric acid, demonstrat ing conjugation of the aromatic amino group. The data appeared to conform with subsequent results obtained for the metabolism of AAF by Westfall and Morris (15). These investigators showed that only 32 per cent of ingested AAF could be re covered 4 hours after administration if it was de termined by diazotization and coupling with so dium 2-naphthol-3,6-disulfonate (R-salt) after previous hydrolysis with hydrochloric acid. It ap peared that the compound had been altered dur ing metabolism in such a manner as to be no longer diazotizable. The present study extends the observations of Westfall (14), concerning the metabolism and dis-