Affiliation:
1. Department of Community, Occupational and Family Medicine, National University of Singapore, Kent Ridge, Singapore 119074
Abstract
Benzene is myelotoxic and leukemogenic in humans. The mechanisms leading to these effects, however have not been fully elucidated. One of the underlying mechanisms is believed to be the oxidative damage caused by its metabolites. A comparative study was undertaken to examine the relationships between reactive oxygen species (ROS) production, lipid peroxidation and subse quent cytotoxicity induced by five major benzene meta bolites. The generation of ROS by benzene metabolites was demonstrated by the significant and dose-dependent increase of intracellular ROS formation in HL60 human promyelocytic leukemia cells in vitro. 1,4-Benzoquinone (BQ) was found to be the most potent metabolite in induction of ROS formation, followed by 1,2,4-benzene triol (BT) and to a lesser extent, phenol (PH) and trans, trans-muconaldehyde (MD). No significant effect was observed when the cells were treated with trans, trans-muconic acid (MA). The enhancement of ROS production by BQ was effectively inhibited by the addition of catalase, deferoxamine (DFO) and dimethyl sulfoxide (DMSO), but unchanged by superoxide dismutase (SOD), suggest that hydrogen peroxide (H2O2) and hydroxyl radicals (OH.) are the two major forms of ROS involved. The results also demonstrate that the ability of benzene metabolites in enhancing ROS generation is closely correlated to their capacity in causing lipid peroxidation and subsequent cytotoxicity. These findings together with earlier parallel observations on DNA damage suggest that ROS play an important role in the mechanism of carcinogenesis induced by benzene metabolites.
Subject
Health, Toxicology and Mutagenesis,Toxicology,General Medicine
Reference26 articles.
1. Recent Advances in the Metabolism and Toxicity of Benzene
2. Goldstein BD, Witz G., Benzene. In: Environmental toxicants, human exposure and their health effects. Lippman M (ed), Van Nostrand Reinhold, New York; 1992; pp. 76-97.
3. Potential role of free radicals in benzene-induced myelotoxicity and leukemia
4. Bus JS, Gibson JE Lipid peroxidation and its role in toxicology. In: Reviews in Biochemical Toxicology. Hodgson E, Bend J, Philpot R (eds.), Elsevier, Amsterdam, 1979; Volume. 1; pp 125-149.
Cited by
76 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献