Carcinogenesis Advance Access originally published online on March 14, 2007
Carcinogenesis 2007 28(11):2363-2366; doi:10.1093/carcin/bgm057
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Increased formation of hepatic N2-ethylidene-2'-deoxyguanosine DNA adducts in aldehyde dehydrogenase 2-knockout mice treated with ethanol
Graduate School of Global Environmental Studies, Kyoto University, Kyoto 606-8501, Japan
1 Department of Social and Environmental Medicine, Saga Medical School, Saga 849-8501, Japan
2 Department of Environmental Biosciences, Yokohama City University, Yokohama, Kanagawa 236-0027, Japan
3 Department of Pharmacological Sciences, State University of New York at Stony Brook, Stony Brook, NY 11794-8651, USA
4 Department of Environmental Health, University of Occupational and Environmental Health, Kitakyusyu, Fukuoka 807-8555, Japan
5 First Department of Biochemistry, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka 431-3192, Japan
6 Department of Molecular and Cellular Biology, Medical Institute of Bioregulation, Kyusyu University, Fukuoka 812-8582, Japan
* To whom correspondence should be addressed. Tel: +75 753 5052 Fax: +81 75 753 3335; Email: matsuda{at}eden.env.kyoto-u.ac.jp
Correspondence may also be addressed to Masayoshi Ichiba. Fax: +81 952 34 2065; Email: ichiba{at}cc.saga-u.ac.jp
N2-ethylidene-2'-deoxyguanosine (N2-ethylidene-dG) is a major DNA adduct induced by acetaldehyde. Although it is unstable in the nucleoside form, it is relatively stable when present in DNA. In this study, we analyzed three acetaldehyde-derived DNA adducts, N2-ethylidene-dG, N2-ethyl-2'-deoxyguanosine (N2-Et-dG) and 
-methyl-
-hydroxy-1,N2-propano-2'-deoxyguanosine (-Me--OH-PdG) in the liver DNA of aldehyde dehydrogenase (Aldh)-2-knockout mice to determine the influence of alcohol consumption and the Aldh2 genotype on the levels of DNA damage. In control Aldh2+/+ mice, the level of N2-ethylidene-dG adduct in liver DNA was 1.9 ± 0.7 adducts per 107 bases and was not significantly different than that of Aldh2+/– and –/– mice. In alcohol-fed mice (20% ethanol for 5 weeks), the adduct levels of Aldh2+/+, +/– and –/– mice were 7.9 ± 1.8, 23.3 ± 4.0 and 79.9 ± 14.2 adducts per 107 bases, respectively, and indicated that adduct level was alcohol and Aldh2 genotype dependent. In contrast, an alcohol- or Aldh2 genotype-dependent increase was not observed for -Me--OH-PdG, and N2-Et-dG was not detected in any of the analyzed samples. In conclusion, the risk of formation of N2-ethylidene-dG in model animal liver in vivo is significantly higher in the Aldh2-deficient population and these results may contribute to our understanding of in vivo adduct formation in humans.
Abbreviations: ADH, alcohol dehydrogenase; ALDH, aldehyde dehydrogenase; 
dA, 1,N6-etheno-2'-deoxyadenosine; LC/MS/MS, liquid chromatography tandem mass spectrometry; -Me--OH-PdG, -methyl--hydroxy-1,N2-propano-2'-deoxyguanosine; N2-Et-dG, N2-ethyl-2'-deoxyguanosine; N2-ethylidene-dG, N2-ethylidene-2'-deoxyguanosine
Received November 13, 2006; revised February 22, 2007; accepted March 2, 2007.