Ethanol-Induced Oxidative DNA Damage and CYP2E1 Expression in Liver Tissue of Aldh2 Knockout Mice
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概要
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Ethanol-Induced Oxidative DNA Damage and CYP2E1 Expression in Liver Tissue of Aldh2 Knockout Mice : Yong-Dae KIM, et al. Department of Preventive Medicine and Medical Research Institute, College of Medicine, Chungbuk National University, Republic of Korea-Excessive alcohol consumption is associated with increased risks of many diseases including cancer. We evaluated oxidative DNA damage in Aldh2 +/+ and Aldh2 -/- mice after they had been subjected to acute ethanol exposure. Olive tail moment, which was measured using a comet assay, was not increased by ethanol treatment in both Aldh2 +/+ and Aldh2 -/- mice. However, after controlling for the effect of ethanol exposure, the Aldh2 genotype was a significant determinant for Olive tail moments. Although the ethanol treatment significantly increased the hepatic 8-OHdG generation in only Aldh2 +/+ mice, the level of 8-OHdG was the highest in Aldh2 -/- ethanol treated mice. The increase in the level of 8-OHdG was associated with hepatic expression of cytochrome P450 2E1 (CYP2E1). The levels of Olive tail moment and the hepatic 8-OHdG in the Aldh2 -/-control group were significantly higher than those of the Aldh2 +/+ control group. The level of CYP2E1 in liver tissue showed a similar pattern to those of the oxidative DNA damage markers. This study shows that acute ethanol consumption increases oxidative DNA damage and that expression of CYP2E1 protein may play a pivotal role in the induction of oxidative DNA damage. The finding that oxidative DNA damage was more intense in Aldh2 -/- mice than in Aldh2 +/+ mice suggests that ALDH2-deficient individuals may be more susceptible than wild-type ALDH2 individuals to ethanol-mediated liver disease, including cancer.
- 社団法人日本産業衛生学会の論文
著者
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小山 倫浩
産業医科大学医学部衛生学
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ZHANG Yan
Department Molecular Oral Medicine and Maxillofacial Surgery, Division of Frontier Medical Science,
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Kim Yong‐dae
Department Of Preventive Medicine College Of Medicine Chunbuk National University
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Kim Yong-dae
Department Of Preventive Medicine College Of Medicine Chunbuk National University
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Kang Jong-won
Department Of Preventive Medicine And Medical Research Institute College Of Medicine Chungbuk Nation
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KAWAMOTO Toshihiro
Department of Environmental Health, University of Occupational and Environmental Health
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Oyama Tsunehiro
Department Of Chest Surgery Kitakyushu Municipal Medical Center
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OGAWA Masanori
Department of Environmental Health, University of Occupational and Environmental Health
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ISSE Toyohi
Department of Environmental Health, University of Occupational and Environmental Health
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KIM Heon
Department of Preventive Medicine, College of Medicine, Chungbuk National University
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EOM Sang-Yong
Department of Preventive Medicine and Medical Research Institute, College of Medicine, Chungbuk Nati
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Kim Heon
Dep. Of Preventive Medicine Coll. Of Medicine Chunbuk National Univ.
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Kim Heon
Department Of Preventive Medicine College Of Medicine Chungbuk National University
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Kim Heon
Department Of Mechanical And Biomedical Engineering Kangwon National University
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Kim Y‐d
Univ. Occupational And Environmental Health Kitakyushu
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Kim Yong-dae
Department Of Computer And Communication Engineering Chungbuk National University
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Eom Sang-yong
Department Of Preventive Medicine And Medical Research Institute College Of Medicine Chungbuk Nation
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Zhang Yan
Department Of Preventive Medicine And Medical Research Institute College Of Medicine Chungbuk Nation
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Isse Toyohi
Department Of Environmental Health School Of Medicine University Of Occupational And Environmental H
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Osaki Toshiro
The Department Pf Surgery Ii School Of Medicine University Of Occupational And Environmental Health.
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Kawamoto Toshihiro
Department Of Environmental Health School Of Medicine University Of Occupational And Environmental H
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Kawamoto Toshihiro
Dep. Of Environmental Health Univ. Of Occupational And Environmental Health
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Ogawa Masanori
Department Of Environmental Health School Of Medicine University Of Occupational And Environmental H
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