Increased formation of gastric N2-ethylidene-2′-deoxyguanosine DNA adducts in aldehyde dehydrogenase-2 knockout mice treated with ethanol

We analyzed an acetaldehyde-derived DNA adduct, N2-ethylidene-2′-deoxyguanosine (N2-Eti-dG) in stomach DNA of aldehyde dehydrogenase (Aldh)-2-knockout mice that were fed with alcohol to determine effects of alcohol consumption and Aldh2 genotype on the level of DNA damage in stomach. Aldh2-active(+/+), heterozygote(+/−) and knockout(−/−) mice were fed 20% ethanol for 5 weeks, then the level of N2-Eti-dG in stomach was determined by liquid chromatography tandem mass spectrometry. The average N2-Eti-dG level in DNA from untreated mice was not significantly different among Aldh2 genotypes (2.0–3.1 adducts/107 bases), however, the average N2-Eti-dG level in DNA from ethanol-treated mice was 4.8 ± 2.6 adducts/107 bases in Aldh2+/+ mice, 7.9 ± 1.1 adducts/107 bases in Aldh2+/− mice, and 48.6 ± 12.0 adducts/107 bases in Aldh2−/− mice, respectively. Our data clearly showed that alcohol drinking caused DNA damage in stomach, which was Aldh2 genotype-dependent in this experimental animal model. This result suggests that heavy-alcohol drinking and Aldh2 deficiency might be risk factors of stomach cancer.