Activation of nuclear receptors by non-genotoxic liver cancer-inducing chemicals

Abstract

Nuclear receptors AHR, CAR, PPARα and PXR are involved in hepatocyte proliferation and chemical hepatocarcinogenesis, but the precise mechanisms are unknown. In this study, we investigated the ability of liver cancer-inducing agrochemicals on the activation of those nuclear receptors. Among the 35 agrochemicals that were selected as non-genotoxic carcinogens based on rat carcinogenicity test results, 6, 18, 4 and 20 chemicals activated AHR, CAR, PPARα and PXR, suggesting that CAR significantly contributes to liver tumor formation via non-genotoxic mechanisms.