Species variation in bladder cell and liver cell activation of acetylaminofluorene

The metabolism and mutagenicity of 2-acetylaminofluorene were measured using freshly prepared intact bladder and liver cells from the cow, dog and rat. High pressure liquid chromatography was used to separate 2-acetylaminofluorene metabolites, andSalmonella typhimurium, strain TA98, was used to detect mutagenic intermediates. Species differences as well as animal-to-animal variation within a species were observed. Mutagenic activity with 2-acetylaminofuorene was greater with cow bladder cells than with dog or rat bladder cells. However, dog bladder cells were most active in metabolizing 2-acetylaminofluorene, and rat bladder cells were least active. Liver cells from all three species metabolized 2-acetylaminofluorene to mutagens forSalmonella, with dog and cow cells being more active than rat liver cells. However, cow liver cells were the most active in metabolizing 2-acetylaminofuorene, followed by rat and dog cells. With all cell types studied, except rat bladder cells, aminofluorene was the major metabolite detected. Carbon and N-hydroxylated products were produced by liver and bladder cells of the three species and glucuronide and sulfate conjugates of the metabolites were detected from both cell types. Correlations between mutagenic activity and the level of metabolism or any individual metabolite were not apparent. The data suggest that the relative contribution of bladder cell metabolism in aromatic amine induced bladder cancer may vary with the species.Abbreviations AAF 2-acetylaminofluorene - 4-ABP 4-aminobiphenyl - AF aminofluorene - BZ benzidine - cytochrome P-450 a collective term for all forms of the cytochrome P-450 polysubstrate mono-oxygenases - FMO flavin mono-oxygenases - HPLC high pressure liquid chromatography - MNNG N-methyl-N-nitro-N-nitrosoguani-dine - 2-NA 2-naphthylamine - N-OH-AAF N-hydroxy-2-acetylaminofluorene - 1-OH-AAF 1-hydroxy-2-acetylaminofluorene - 5-OH-AAF 5-hydroxy-2-acetylaminofluorene - 7-OH-AAF 7-hydroxy-2-acetylaminofluorene - 8OH-AAF 8-hydroxy-2-acetylaminofluorene - 9-OH-AAF 9-hydroxy-2-acetylaminofluorene - UDS unscheduled DNA synthesis