Increased formation of hepatic N-2-ethylidene-2'-deoxyguanosine DNA adducts in aldehyde dehydrogenase 2-knockout mice treated with ethanol
| Autor: | Kentaro Misaki, Katsumaro Tomokuni, Toshihiro Kawamoto, Tomonari Matsuda, Masayoshi Ichiba, Shinya Shibutani, Akiko Matsumoto, Keiichi I. Nakayama, Mitsuhiro Uchida, Kyoko Kitagawa, Robert A. Kanaly |
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| Jazyk: | angličtina |
| Rok vydání: | 2007 |
| Předmět: |
Male
Cancer Research DNA damage Population Aldehyde dehydrogenase Adduct DNA Adducts Mice chemistry.chemical_compound Tandem Mass Spectrometry DNA adduct Animals Deoxyguanosine education ALDH2 Mice Knockout education.field_of_study Ethanol biology Aldehyde Dehydrogenase Mitochondrial Acetaldehyde General Medicine Aldehyde Dehydrogenase Mice Inbred C57BL Liver chemistry Biochemistry biology.protein Chromatography Liquid |
| Zdroj: | CARCINOGENESIS. 28(11):2363-2366 |
| ISSN: | 0143-3334 |
| Popis: | 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 alpha-methyl-gamma-hydroxy-1,N2-propano-2'-deoxyguanosine (alpha-Me-gamma-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 10(7) 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 10(7) 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 alpha-Me-gamma-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. |
| Databáze: | OpenAIRE |
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