title: Ethanol-induced oxidative DNA damage and CYP2E1 expression in liver tissue of Aldh2 knockout mice.
abstract: 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.
authors.affiliation: Department of Preventive Medicine and Medical Research Institute, College of Medicine, Chungbuk National University, Republic of Korea.
authors.forename: Yong-Dae
authors.initials: YD
authors.lastname: Kim
authors.forename: Sang-Yong
authors.initials: SY
authors.lastname: Eom
authors.forename: Masanori
authors.initials: M
authors.lastname: Ogawa
authors.forename: Tsunehiro
authors.initials: T
authors.lastname: Oyama
authors.forename: Toyohi
authors.initials: T
authors.lastname: Isse
authors.forename: Jong-Won
authors.initials: JW
authors.lastname: Kang
authors.forename: Yan Wei
authors.initials: YW
authors.lastname: Zhang
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Kawamoto
authors.forename: Heon
authors.initials: H
authors.lastname: Kim
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000444:Aldehyde Dehydrogenase / Q000172:deficiency / Q000235:genetics*; D000071396:Aldehyde Dehydrogenase, Mitochondrial; D000704:Analysis of Variance; D000818:Animals; D015153:Blotting, Western; D056486:Chemical and Drug Induced Liver Injury; D020552:Comet Assay; D019392:Cytochrome P-450 CYP2E1 / Q000032:analysis / Q000235:genetics*; D004249:DNA Damage / Q000235:genetics*; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000032:analysis / Q000235:genetics; D004195:Disease Models, Animal; D000431:Ethanol / Q000633:toxicity*; D020022:Genetic Predisposition to Disease; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D008107:Liver Diseases / Q000235:genetics*; D008297:Male; D051379:Mice; D018345:Mice, Knockout / Q000235:genetics; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology; D018384:Oxidative Stress / Q000187:drug effects / Q000235:genetics*; D011110:Polymorphism, Genetic
chemical_list: D000431:Ethanol; D000080242:8-Hydroxy-2'-Deoxyguanosine; D019392:Cytochrome P-450 CYP2E1; C515029:ALDH2 protein, mouse; D000444:Aldehyde Dehydrogenase; D000071396:Aldehyde Dehydrogenase, Mitochondrial; D003849:Deoxyguanosine