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Journal of Environmental Toxicology 2007;22(4):357-366.
산화적 스트레스에 의한 N"-methyl-N"-nitroguanidine의 유전독성증가
강진석, 정기경, 서수경, 김주환, 이화옥, 정해관, 김승희, 박순희
Increased Genotoxicity of N"-methyl-N"-nitroguanidine by Oxidative Stress
Jin Seok Kang , Ki Kyung Jung , Soo Kyung Suh , Joo Hwan Kim , Hwa Ok Lee , Hai Kwan Jung , Seung Hee Kim , Sue Nie Park
ABSTRACT
  To investigate the possible enhancement of genotoxicity in stress environment, we examined the effect of genotoxic material in oxidative stress-induced condition using human cell line. Human lymphoblast cell line, TK6 was treated with hydrogen peroxide (H₂O₂) for induction of oxidative stress, and treated with N’-methyl-N’-nitroguanidine (MNNG), as a genetoxic material. We carried out MTS assay to set treatment doses. TK6 was treated with H₂O₂ as 6.75 (low dose) or 13.5 ?M (high dose) for 2 h, and treated with MNNG as 0.117 (low dose), 0.234 (middle dose), 0.468 ?M (high dose) for 2 h. As results, a treatment of MNNG induced DNA damage as dose dependently. And TK6 treated with H₂O₂ 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 H₂O₂ and MNNG treated groups. Real-time RT-PCR analyses for expression sion of several antioxidative enzymes showed that catalase mRNA and glutathione peroxidase 1 mRNA expression were decreased in H₂O₂ and MNNG treated groups. Taken together, we conclude that genotoxicity induced by MNNG is enhanced in a condition of oxidative stress induced by H₂O₂ and it suggests that it should be associated with induction of lipid peroxidation and decrease of antioxidant enzymes.
Keywords: genotoxicity; oxidative stress; hydrogen peroxide(H₂O₂); N"; -methyl-N"; -nitroguanidine(MNNG); TK6 cell line
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