Evaluation of the rat CAR activation for the prediction of chemical liver carcinogenesis

Abstract

Activation of the nuclear receptor CAR induces liver cancer in rodents, and thus the information on whether a chemical compound activates CAR or not is useful for predicting its carcinogenicity. In this study, we treated rat primary hepatocytes with around 300 test compounds and found that 106 compounds increased mRNA levels of Cyp2b1, a typical CAR target gene, more than 10-fold. Among them, 18 activated the mutant CAR, which we constructed to repress its constitutive activity, in reporter assays. These methods might be useful to evaluate CAR activation of chemical compounds.