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Abstract
The procarcinogen benzo[a]pyrene (B[a]P) requires metabolic activation by cytochrome P450s (P450s) and epoxide hydrolase (EH). In the present study, we define the role of each of seven cDNA-expressed human P450s in the metabolism of B[a]P. In the lymphoblastoid cells (AHH-1), 1A1 and A1+EH metabolize B[a]P at rates of 7–12 times greater than that for 1A2 and 3A4. EH was shown to be directly involved in B[a]P activation. Of the P450s expressed from the vaccinia virus vectors, 1A2 and 2C9 showed the highest activity. The seven P450s used were found to stereoselectively form R,R-dihydrodiols enriched in 80–100%. These studies determined the capacity of individual human P450 in the metabolism and activation of B[a]P and can lead to understanding the P450 control of detoxifying and activating polycyclic aromatic hydrocarbons.