Interspecies comparison of liver carcinogenesis: implications for cancer risk assessment.

The morphology of hepatocellular carcinoma is similar among mice, rats and humans, and the cellular pathogenesis shows features that are both similar and divergent among these species. However, major elements of etiology, molecular pathogenesis, and natural history differ between humans and rodents. As a reflection of these species-determined differences, rodents appear to be neither highly sensitive nor highly specific surrogates for detecting agents that are potential causes of hepatocellular cancer in humans. Results of tests of chemical carcinogenicity in rodents are likely to include a significant number of both false-positive and false-negative risks for humans.