Role of Aryl Hydrocarbon Receptor-mediated Induction of the CYP1 Enzymes in Environmental Toxicity and Cancer

The mammalian CYP1A1, CYP1A2, and CYP1B1 genes (encoding cytochromes P450 1A1, 1A2, and 1B1, respectively) are regulated by the aromatic hydrocarbon receptor (AHR). The CYP1 enzymes are responsible for both metabolically activating and detoxifying numerous polycyclic aromatic hydrocarbons (PAHs) and aromatic amines present in combustion products. Many substrates for CYP1 enzymes are AHR ligands. Differences in AHR affinity between inbred mouse strains reflect variations in CYP1 inducibility and clearly have been shown to be associated with differences in risk of toxicity or cancer caused by PAHs and arylamines. Variability in the human AHR affinity exists, but differences in human risk of toxicity or cancer…