Effect of paraoxon‐methyl and parathion‐methyl on DNA in human lymphocytes and protective action of vitamin C

J. Błasiak, J. Kowalik
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引用次数: 16

Abstract

The molecular basis of the genotoxicity of the commonly used organophosphorus insecticide, parathion-methyl is poorly understood and there is a lack of information on the possible effects of its metabolic conversion products. In the present work the action of parathion-methyl and its immediate metabolite paraoxon-methyl on DNA in human lymphocytes was compared using the comet assay. Parathion-methyl at 25 and 75 µM did not cause any significant changes but at 200 µM a significant increase in the tail moment was observed as compared with the control. Paraoxon-methyl at 25, 75 and 200 µM evoked dose-dependent DNA damage measured as a significant increase in comet tail moment of lymphocytes. The change evoked by paraoxon-methyl at 200 µM was much more pronounced than that by parathion-methyl at the same concentration. To search for the mechanism underlying the observed effect, the action of a well-known antioxidant, vitamin C, along with parathion-methyl and paraoxon-methyl was studied. The vitamin at 10 and 50 µM reduced the DNA-damaging activity of paraoxon-methyl at all its concentrations. The results indicate that the reported genotoxic effects of parathion-methyl could be mainly attributed to its metabolite paraoxon-methyl. The protective action of vitamin C suggests that paraoxon-methyl may cause oxidative DNA damage. © 1999 Society of Chemical Industry
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甲基对硫磷和甲基对硫磷对人淋巴细胞DNA的影响及维生素C的保护作用
人们对常用的有机磷杀虫剂甲基对硫磷遗传毒性的分子基础了解甚少,对其代谢转化产物可能产生的影响也缺乏信息。本文用彗星法比较了甲基对硫磷及其直接代谢物甲基对硫磷对人淋巴细胞DNA的作用。甲基对硫磷在25和75µM时没有引起任何显著变化,但在200µM时,与对照相比,尾部力矩显著增加。25、75和200µM的甲基对氧磷引起了剂量依赖性的DNA损伤,淋巴细胞彗尾时刻显著增加。在200µM浓度下,甲基对硫磷引起的变化比相同浓度的甲基对硫磷引起的变化更明显。为了寻找观察到的效应背后的机制,研究了一种众所周知的抗氧化剂维生素C与甲基对硫磷和甲基对氧磷的作用。10µM和50µM的维生素降低了所有浓度的甲基对氧磷的dna损伤活性。结果表明,甲基对硫磷的遗传毒性作用可能主要归因于其代谢物甲基对硫磷。维生素C的保护作用提示甲基对氧磷可能引起DNA氧化损伤。©1999化学工业学会
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