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.