Journal Article

Increased formation of hepatic <i>N</i><sup>2</sup>-ethylidene-2′-deoxyguanosine DNA adducts in <i>aldehyde dehydrogenase 2</i>-knockout mice treated with ethanol

Tomonari Matsuda, Akiko Matsumoto, Mitsuhiro Uchida, Robert A. Kanaly, Kentaro Misaki, Shinya Shibutani, Toshihiro Kawamoto, Kyoko Kitagawa, Keiichi I. Nakayama, Katsumaro Tomokuni and Masayoshi Ichiba

in Carcinogenesis

Volume 28, issue 11, pages 2363-2366
Published in print November 2007 | ISSN: 0143-3334
Published online March 2007 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/bgm057
Increased formation of hepatic N2-ethylidene-2′-deoxyguanosine DNA adducts in aldehyde dehydrogenase 2-knockout mice treated with ethanol

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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 α-methyl-γ-hydroxy-1,N2-propano-2′-deoxyguanosine (α-Me-γ-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 α-Me-γ-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.

Journal Article.  3109 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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