Mode of action and human relevance for Amisulbrom-induced rodent liver tumors

Abstract

To investigate the mode of action (MoA) and human relevance of Amisulbrom-induced liver tumors in rodent, we conducted two experiments using CAR KO rats and chimeric mice with humanized liver. Increases of liver Cyp2b or CYP2B6 mRNA levels were observed in the wild type rats and chimeric mice, but not in the CAR KO rats. Increase of hepatocellular proliferation were observed in the wild type rats, but not in the CAR KO rats and chimeric mice. These results suggest that Amisulbrom-induced liver tumors are mediated by CAR activation and the MoA for rodent liver tumors is not relevant to humans.