The N- and Ring-Hydroxylation of 2-Acetylaminofluorene during Carcinogenesis in the Rat* JAMES

The new major metabolite of @-acetylaminofluorene (AAF) in the rat, N-hydroxy AAF, was excreted in the urine as a conjugate in amounts that increased during car cinogenesis; the amount at 18 weeks was about 9 times that at 1@weeks. When 3methylcholanthrene, which greatly inhibits the carcinogenicity of AM?, was fed with AAF, the excretion of N-hydroxy-AAF remained low, while the excretion of 3and 5-hydroxy-AAF was increased and that of 7-hydroxy-AAF was essentially unaltered. The urine of guinea pigs fed AM' did not contain detectable amounts of N-hydroxy AAF. Mice excreted the compound in smaller amounts than did rats. Evidence obtained with @-(acetyl-1'-C'4)aminofluorene in vivo demonstrated that N-hydroxy-AAF and 1-, 3-, 5-, and 7-hydroxy-AAF are either formed directly from AAF or arise via derivatives of AAF which retain the acetyl group. Administration of N-hydroxy-AAF resulted in the urinary excretion of AAF and 1-, 3-, 5-, and 7-hydroxy AAF. 1-Hydroxy-AAF may be formed by rearrangement of an o-quinolimide derivable from N-hydroxy-AAF. N..Hydroxylation may play an important role in the metabolism and carcinogenicity of many amines.