Characterization of cytochrome P450 2E1 activity by the [C-14]nitrosodimethylamine breath test

The objective of this study was to measure the rate of demethylation of nit rosodimethylamine in vivo in the rat and determine its value to assess CYP2 E1 activity in intact animals. Nitrosodimethylamine labeled with C-14 On bo th methyl groups was administered to rats and exhaled (CO2)-C-14 was collec ted during 2-3 h. The nitrosodimethylamine breath test was increased by ind ucers of CYP2E1, such as ethanol (+139%) and 4-methylpyrazole (+115%), and decreased by the inhibitor diallyl sulfide (-53%). In addition, the nitroso dimethylamine breath test was not changed significantly by inducers specifi c for other cytochrome P450 such as beta-naphthoflavone, dexamethasone, and phenobarbital. The specificity of the induction by 4-methylpyrazole and of the inhibition by diallyl sulfide for CYP2E1 was determined using the [C-1 4]caffeine (CYP1A2), [C-14]aminopyrine (CYP2C11), and [C-14]erythromycin (C YP3A2) breath tests. 4-Methylpyrazole treatment caused a small increase of the caffeine (+33%) and aminopyrine (+9%) breath tests and no change of the erythromycin breath test. Diallyl sulfide treatment led to a small decreas e of the caffeine breath test (-33%) and of the aminopyrine breath test (-1 3%) but a 23% increase of the erythromycin breath test. It is concluded tha t the [C-14]nitrosodimethylamine breath test is useful to assess CYP2E1 act ivity in vivo in the rat.