N-Hydroxylation of 2-Acetylaminofluorene in the Rabbit

Abstract

Summary The major urinary metabolites of 2-acetylaminofluorene (AAF) in the rabbit were N-hydroxy-2-acetylaminofluorene and 7-hydroxy-2-acetylaminofluorene. By the third day of AAF feeding (70 mg AAF/day), N-hydroxy-2-acetylaminofluorene was the predominant urinary metabolite, and its excretion accounted for 22–30 per cent of the daily dose of ingested AAF during the first 4 weeks of feeding. During this same time interval, 12–28 per cent of the dose of AAF per day was excreted as 7-hydroxy-2-acetylaminofluorene. Only small (0.5–1.5 per cent of dose) or trace (0.1–0.5 per cent of dose) amounts of 3-hydroxy-2-acetylaminofluorene and 5-hydroxy-2-acetylaminofluorene were excreted. The rabbits did not excrete detectable quantities (more than 0.1 per cent of dose) of 1-hydroxy-2-acetylaminofluorene. N-Hydroxy-2-acetylaminofluorene was excreted entirely as a conjugate which was hydrolyzed by bacterial β-glucuronidase. 7-Hydroxy-2-acetylaminofluorene was excreted mainly as a conjugate cleaved by β-glucuronidase; in addition, however, small amounts of the unconjugated form or the ethereal sulfate were excreted.