AHR and hepatocellular carcinoma: It also has been suggested that a second level of negative feedback within the AHR circuit is likely mediated by AHR induction of prototypic target genes such as CYP1A1 and CYP1B1. In 2004, it was shown that pharmacological inhibition of CYP1A1 increased baseline AHR activity in rat hepatoma cells through the inhibition of CYP1-mediated catabolism of endogenous AHR agonist(s) [161].