Metabolic fate and disposition of 2-acetylaminofluorene in rainbow trout, Oncorhynchus mykiss

Rainbow trout, Shasta strain, in contrast to several mammalian species, are highly resistant to hepatocarcinogenesis by 2-acetylaminofluorene (AAF). In order to examine factors that may contribute to this resistance, we investigated the metabolic fate of AAF. Trout treated orally with [ 14C]AAF rapidly eliminated AAF derivatives via the liver (in which the concentration of AAF-derived radioactivity decreased 4-fold between 8 and 24 h) into the bile which, at 24 h, contained 83% of the recovered radioactivity. At 24 h only 3.5% of the AAF-derived radioactivity retained by the liver represented unmetabolized AAF. In the bile, unmetabolized AAF and 2-aminofluorene accounted for 3.3% and 4.8%, respectively, of total biliary radioactivity, while glucuronide and sulfate conjugates accounted for 63% and 12%, respectively. Analysis of extracts of the deconjugated metabolites revealed that conjugates of 7-OH-AAF and 5-/8-/9-OH-AAF accounted for 49% and 14%, respectively, of total radioactivity. The potentially carcinogenic metabolite N-OH-AAF occurred predominately as the glucuronide conjugate which amounted to only 2% of total metabolites. These data demonstrate that the liver of Shasta trout is highly efficient in the detoxification and elimination of AAF and its derivatives.