AhR and Nrf2 as Key Molecules in Xenobiotic Detoxification

Our health is always threatened by various xenobiotics in our daily life. In order to protect our bodies from these exogenous reagents, several detoxifying enzymes are induced by xenobiotic ingestion. Detoxifying enzymes are regulated at the transciption level and AhR and Nrf2 are the major regulators of Phase I and Phase II enzymes, respectively. AhR-null mutatnt mice, Nrf2-null mutant mice, AhR-overexpressing mice, and Nrf2-overexpressing mice are all available in our laboratory. We are also generating compound mutant mice in various combinations. These mutant mice provide us with advantageous experimental systems to study the transcriptional regulation of the detoxification reaction. Our goal in this study is to clarify the functional contribution of a battery of genes regulated by AhR or Nrf2 in the protective response against xenobiotics.