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J Occup Health year 2007 volume 49 number 5 page 363 - 369
Classification Original
Title Ethanol-Induced Oxidative DNA Damage and CYP2E1 Expression in Liver Tissue of Aldh2 Knockout Mice
Author Yong-Dae KIM1, Sang-Yong EOM1, Masanori OGAWA2, Tsunehiro OYAMA2, Toyohi ISSE2, Jong-Won KANG1, Yan Wei ZHANG1, Toshihiro KAWAMOTO2 and Heon KIM1
Organization 1Department of Preventive Medicine and Medical Research Institute, College of Medicine, Chungbuk National University, Republic of Korea and 2Department of Environmental Health, University of Occupational and Environmental Health, Japan
Keywords Aldehyde dehydrogenase 2, Cytochrome P450 2E1, Oxidative stress, Olive tail moment, 8-Hydroxydeoxyguanosine
Correspondence H. Kim, Department of Preventive Medicine, College of Medicine, Chungbuk National University, 12 Gaeshin-dong, Heungdok-gu, Cheongju, Chungbuk 361-763, Republic of Korea (e-mail: kimheon@cbu.ac.kr)
Abstract 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.