The N- and ringhydroxylation of 2-acetylaminofluorene during carcinogenesis in the rat.

Abstract

The new major metabolite of 2-acetylaminofluorene (AAF) in the rat, N -hydroxy-AAF, was excreted in the urine as a conjugate in amounts that increased during carcinogenesis; the amount at 18 weeks was about 9 times that at 1½ weeks. When 3-methylcholanthrene, which greatly inhibits the carcinogenicity of AAF, was fed with AAF, the excretion of N -hydroxy-AAF remained low, while the excretion of 3- and 5-hydroxy-AAF was increased and that of 7-hydroxy-AAF was essentially unaltered. The urine of guinea pigs fed AAF did not contain detectable amounts of N -hydroxy-AAF. Mice excreted the compound in smaller amounts than did rats. Evidence obtained with 2-(acetyl-1′-C14)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.