Epoxidation of acrylonitrile by rat and human cytochromes P450

The cytochromes P450 (P450) involved in the epoxidation of the rat carcinogen acrylonitrile (ACN) to the mutagen 2-cyanoethylene oxide (CEO) have been investigated in hepatic microsomes from F-344 rats and humans. Induction of P450 2E1 by acetone treatment increased the V max for rat microsomal CEO formation 5-fold, while ACN treatment had little effect. Treatment with β-naphthoflavone, dexamethasone, and phenobarbital had little effect upon V max but increased the K M 3- to 5-fold. The P450 ligand 1-phenylimidazole and substrate ethanol were potent inhibitors of ACN epoxidation after all treatments