Increased formation of hepatic N super(2)-ethylidene-2'-deoxyguanosine DNA adducts in aldehyde dehydrogenase 2-knockout mice treated with ethanol

N super(2)-ethylidene-2'-deoxyguanosine (N super(2)-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, N super(2)-ethylidene-dG, N super(2)-ethyl-2'-deoxyguanosine (N super(2)-Et-dG) and alpha -methyl- gamma -hydroxy-1,N super(2)-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 N super(2)-ethylidene-dG adduct in liver DNA was 1.9 plus or minus 0.7 adducts per 10 super(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 plus or minus 1.8, 23.3 plus or minus 4.0 and 79.9 plus or minus 14.2 adducts per 10 super(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 N super(2)-Et-dG was not detected in any of the analyzed samples. In conclusion, the risk of formation of N super(2)-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.