Human hepatocyte and kidney cell metabolism of 2-acetylaminofluorene and comparison to the respective rat cells.
The metabolism and mutagenic activation of 2-acetylaminofluorene by human and rat hepatocytes and kidney cells were measured. High performance liquid chromatography was used to separate the 2-acetylaminofluorene metabolites, and a cell-mediated Salmonella typhimurium mutagenesis assay was used to detect mutagenic intermediates. Rat and human differences were observed with cells from both organs and levels of metabolism and mutagenesis were higher in human cells. Within a species, liver and kidney cell differences were also evident, with levels of hepatocyte-mediated metabolism and mutagenesis being greater than kidney cells. Human inter-individual variation was apparent with cells from both organs, but the variation observed was significantly greater in hepatocytes than kidney cells. A knowledge of such differences, including an understanding that they may vary with the chemical being studied, should be useful in the extrapolation of rodent carcinogenesis data to humans.
Langenbach
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R
Cellular and Genetic Toxicology Branch, National Institute of Environmental Health Sciences Research Triangle Park, North Carolina 27709.
Rudo
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K
D015073:2-Acetylaminofluorene / Q000493:pharmacokinetics / Q000633:toxicity*; D000818:Animals; D001711:Biotransformation; D015197:Carcinogenicity Tests; D005260:Female; D006801:Humans; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009152:Mutagenicity Tests; D051381:Rats; D013045:Species Specificity
D015073:2-Acetylaminofluorene