Cultured primary human and rat hepatocytes are used in our laboratory to assess the potential susceptibility of humans to peroxisome proliferators (PP). PP are a diverse group of nongenotoxic lipid lowering drugs and environmental chemicals, many of which are hepatocarcinogenic upon chronic administration to rodents. Despite the potential for human exposure to PP, susceptibility of humans to these chemicals is poorly characterized. Work in our laboratory was undertaken to assess the risks of humans to PP by comparing the expression of specific marker genes in primary rat and human hepatocytes incubated with PP using quantitative reverse transcriptase polymerase chain reaction (QPCR). Initial investigation focused on the induction of specific transcripts that have been shown to be modulated by PP in the rat, which included liver fatty acid binding protein (L-FABP), acyl-CoA oxidase (AOxase), rat cytochrome P4501A1 and human P4504A11, and peroxisome proliferator activated receptor-alpha (PPARa). In addition, induction of S-phase DNA synthesis in hepatocytes in vitro is investigated in an attempt to determine the functional significance of genes expressed by PP.
