Effect of the microsomal system on quinone redox cycling, oxygen activation, and lipid peroxidation.

Abstract

Our previous results indicated that benzoquinone caused cytochrome P450 destruction 1-3. Metabolites of benzene - catechol, hydroquinone, and paticularly its oxidized form, benzoquinone, exert toxic effects on biomacromolecules, eg by covalent binding to proteins, formation of DNA adducts4 and destruction of cytochrome P450 (CYP) 1.3. Benzene is an established human and animal carcinogens5 acting through an epigenetic mechanism. The main goal of this study was to provide a more detailed insight into toxicology of benzene. Interconversions among hydroquinone (HQ), semiquinone radical (SQ), and benzoquinone (BQ) in both aqueous solutions and in the presence of the microsomal system were followed up. The production of hydroxyl radicals and the initiation of lipid peroxidation was investigated and the role of iron and antioxidant ascorbate was assessed. Microsomes from rats pretreated with CYP2E1 inducer were used in all experiments because this CYP isoform has been suggested to produce enhanced amounts of reactive oxygen species and increased the rate of lipid peroxidation in vitro 6. The results presented here bring an additional evidence for the recently proposed novel mechanism of toxicity induced by metabolites of benzene3.KeywordsLipid PeroxidationElectron Spin ResonanceSemiquinone RadicalMicrosomal SystemBind Transition MetalThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.