Despite major progress in the field of environmental biology and toxicology, assessment of human risk to chemicals is almost exclusively based on data obtained from studies in laboratory animals. We have developed techniques in our laboratory for comparing chemical metabolism, toxicity, and characterization of exposure biomarkers in fresh animal and human tissues in vitro. Our recent studies focused on comparing the expression of cancer biomarker genes by the model rodent hepatocarcinogen, Wy-14,643 (WY), incubated with fresh rat and human hepatocytes. Using quantitative polymerase chain reactions (QPCR), expression of Cytochrome P4504A enzyme, acyl-CoA oxidase, peroxisome proliferators activated receptors (PPAR), liver fatty acid binding protein (LFABP), and proliferator cell nuclear antigens (PCNA) was assessed. We also compared the induction of cell proliferation in rat and human hepatocytes in culture using bromodeoxyuridine incorporation into the DNA of hepatocytes using immunohistochemical staining.