Cytochrome P450 (CYP) enzymes carry out oxidative metabolism of a variety of endogenous and foreign chemicals. Cytochrome P450 2E1 (CYP2E1) is thought to be responsible for the oxidative metabolism of ethanol and a number of other chemicals of importance to the NTP including 1,3-butadiene, benzene, and vinyl chloride.
The aim of the present work is to assess the role of CYP2E1 in the oxidative metabolism and toxicity of acrylonitrile (AN), methacrylonitrile (MAN), and acrylamide (AM) was determined. Wild-type mice (WT), WT mice pretreated with aminobenzotriazole (ABT, 50 mg/kg ip, 2 hr pre- exposure), and mice devoid of cytochrome P450 2E1 (CYP2E1-null) were administered 50 mg/kg [13C]AM po. WT mice and CYP2E1-null mice were administered 2.5 or 10 mg/kg [13C]AN po. Urine was collected for 24 hr, and metabolites were characterized using 13C NMR. WT mice excreted metabolites derived from the epoxides and from direct GSH conjugation with AM or AN. Only metabolites derived from direct GSH conjugation with AM or AN were observed in the urine from ABT-pretreated WT mice and CYP2E1-null mice. - CYP2E1-null mice Acrylonitirle Methacrylonitrile Acrylamide 2-Butoxyethanol Metabolism Disposition
