Effect of paraoxon-methyl and parathion-methyl on DNA in human lymphocytes and protective action of vitamin C
1999
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 micromolar did not cause any significant changes but at 200 micromolar a significant increase in the tail moment was observed as compared with the control. Paraoxon-methyl at 25, 75 and 200 micromolar evoked dose-dependent DNA damage measured as a significant increase in comet tail movement of lymphocytes. The change evoked by paraoxon-methyl at 200 micromolar 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 micromolar 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.
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