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Increased Genotoxicity of N'-methyl-N'-nitroguanidine by Oxidative Stress  

Kang, Jin-Seok (Department of Toxicological Researches, National Institute of Toxicological Research, Korea Food and Drug Administration)
Jung, Ki-Kyung (Department of Toxicological Researches, National Institute of Toxicological Research, Korea Food and Drug Administration)
Suh, Soo-Kyung (Department of Toxicological Researches, National Institute of Toxicological Research, Korea Food and Drug Administration)
Kim, Joo-Hwan (Department of Toxicological Researches, National Institute of Toxicological Research, Korea Food and Drug Administration)
Lee, Hwa-Ok (Department of Toxicological Researches, National Institute of Toxicological Research, Korea Food and Drug Administration)
Jung, Hai-Kwan (Department of Toxicological Researches, National Institute of Toxicological Research, Korea Food and Drug Administration)
Kim, Seung-Hee (Department of Toxicological Researches, National Institute of Toxicological Research, Korea Food and Drug Administration)
Park, Sue-Nie (Department of Toxicological Researches, National Institute of Toxicological Research, Korea Food and Drug Administration)
Publication Information
Environmental Analysis Health and Toxicology / v.22, no.4, 2007 , pp. 357-366 More about this Journal
Abstract
To investigate the possible enhancement of genotoxicity in stress environment, we examined the of effect of genotoxic material in oxidative stress-induced condition using human tell line. Human lymphoblast cell line, TK6 was treated with hydrogen peroxide ($H_2O_2$) for induction of oxidative stress, and treated with N'-methyl-N'-nitroguanidine (MNNG), af a genetoxic material. We carried out MTS assay to set treatment doses. TK6 was treated with $H_2O_2$ at 6.75 (low dote) or $13.5\;{\mu}M$ (high dose) for 2 h, and treated with MNNG af 0.117 (low dose), 0.234 (middle dose), $0.468\;{\mu}M$ (high dose) for 2 h. As results, a treatment of MNNG induced DNA dam age as dose dependently. And TK6 treated with $H_2O_2$ at low as well as high dose followed by MNNG treatment showed higher DNA damage compared to MNNG alone treated groups. Malondialdehyde, as a marker of lipid peroxidation was increased in $H_2O_2$ and MNNG treated groups. Real-time RT-PCR analyses for expression of several antioxidative enzymes showed that catalase mRNA and glutathione peroxidase 1 mRNA expression were decreased in $H_2O_2$ and MNNG treated groups. Taken together, we conclude that genotoxicity induced by MNNG is enhanced in a condition of oxidative stress induced by $H_2O_2$ and it suggests that it should be associated with induction of lipid peroxidation and decrease of antioxidant enzymes.
Keywords
genotoxicity; oxidative stress; hydrogen peroxide ($H_2O_2$); N'-methyl-N'-nitroguanidine (MNNG); TK6 cell line;
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