Metabolism of benzene in human liver microsomes: individual variations in relation to CYP2E1 expression.

In human liver microsomes the oxidations of benzene, chlorzoxazone, aniline, dimethylformamide, and 4-nitrophenol were significantly correlated with each other and with the level of cytochrome P450 (CYP) 2E1 estimated by immunoblotting. Moreover, benzene oxidation to water-soluble metabolites was suppressed by 0.1 mM diethyldithiocarbamate, supposedly a specific inhibitor of CYP2E1 at this level.

Cytochrome P450 catalyzed oxidation of monochlorobenzene, 1,2- and 1,4-dichlorobenzene in rat, mouse, and human liver microsomes.

We studied metabolism of monochlorobenzene (MCB), 1,2-dichlorobenzene (1,2-DCB) and 1,4-DCB in liver microsomes from untreated male and female Wistar rats and B6C3F1 mice or in those after the induction of CYP3A or 2E1 as well as in human male liver microsomes. MCB and 1,2-DCB were oxidised mainly by rat and human CYP2E1. It was found that 1,4-DCB was oxidised by rat and human CYP2E1 at a several-fold lower rate than 1,2-DCB, but a greater part to covalently binding products.

Cytochromes P450 in benzene metabolism and involvement of their metabolites and reactive oxygen species in toxicity.

Cytochrome P450 (CYP) 2E1 was the most efficient CYP enzyme that oxidized benzene to soluble and covalently bound metabolites in rat and human liver microsomes. The covalent binding was due mostly to the formation of benzoquinone (BQ), the oxidation product of hydroquinone (HQ), and was inversely related to the formation of soluble metabolites. In rats, inhalation of benzene (4 mg/liter of air) caused a rapid destruction of CYP2B1 previously induced by phenobarbital.

Effects of acetone on the capacity of o-xylene and toluene to induce several forms of cytochrome P450 in rat liver.

The influence of acetone on the induction of P450 in lung, kidney and liver by toluene and xylene was studied in an attempt to estimate more precisely the range of P450 which are proposed to function in the activation of xylenes and toluene metabolites in the conditions of combined exposures. The addition of acetone potentiated the induction of CYP1A1/2 to 4 minutes ethoxyresorufin deethylation that from control animals after pretreatment with toluene. The level of this enzymatic activity (0.

Interaction of styrene and ethylmethylketone in the induction of cytochrome P450 enzymes in rat lung, kidney and liver after separate and combined inhalation exposures.

The present study compares the induction of different cytochrome P450 forms (CYP1A1/2, 2B1, 2E1) after pretreatment with styrene, ethylmethylketone separately or in combined exposures. Combined exposures lead to cumulative elevation of CYP levels, except for CYP1A1 and 2B1. Induction of CYP1A1 was higher in liver and kidney respectively and did not change significantly with the pretreatment mode.