Increased formation of hepatic N2 -ethylidene-2′-deoxyguanosine DNA adducts in aldehyde dehydrogenase 2-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, Masayoshi Ichiba

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Abstract

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.

Original languageEnglish
Pages (from-to)2363-2366
Number of pages4
JournalCarcinogenesis
Volume28
Issue number11
DOIs
Publication statusPublished - Nov 1 2007

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All Science Journal Classification (ASJC) codes

  • Cancer Research

Cite this

Matsuda, T., Matsumoto, A., Uchida, M., Kanaly, R. A., Misaki, K., Shibutani, S., ... Ichiba, M. (2007). Increased formation of hepatic N2 -ethylidene-2′-deoxyguanosine DNA adducts in aldehyde dehydrogenase 2-knockout mice treated with ethanol. Carcinogenesis, 28(11), 2363-2366. https://doi.org/10.1093/carcin/bgm057