Genotoxic effects of 2-acetylaminofluorene on rat and human hepatocytes.
Isolated rat and human hepatocytes in primary culture were shown to metabolize AAF to reactive intermediates which damaged hepatocyte DNA. A significant increase in unscheduled DNA synthesis was detectable by autoradiography in rat and human hepatocytes exposed to concentrations of AAF as low as 1 microM. When rat hepatocytes were plated over confluent monolayers of human fibroblasts and exposed to 3H-AAF, significant binding of AAF to the DNA of the fibroblasts as well as the hepatocytes was measured. In other experiments with hepatocyte-fibroblast cocultures, nonradioactive AAF, at concentrations greater than 40 microM, induced a significant increase in the HPRT- mutation frequency in the human fibroblasts. These results demonstrate that hepatocytes can be used to assess genotoxicity of carcinogenic compounds and are useful for interspecies comparisons in chemical carcinogenesis.
D015073:2-Acetylaminofluorene / Q000378:metabolism / Q000633:toxicity*; D000818:Animals; D002273:Carcinogens / Q000378:metabolism; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis*; D006801:Humans; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D008297:Male; D051381:Rats; D013045:Species Specificity
D002273:Carcinogens; D004247:DNA; D015073:2-Acetylaminofluorene