Increased formation of gastric N(2)-ethylidene-2'-deoxyguanosine DNA adducts in aldehyde dehydrogenase-2 knockout mice treated with ethanol.
We analyzed an acetaldehyde-derived DNA adduct, N(2)-ethylidene-2'-deoxyguanosine (N(2)-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 N(2)-Eti-dG in stomach was determined by liquid chromatography tandem mass spectrometry. The average N(2)-Eti-dG level in DNA from untreated mice was not significantly different among Aldh2 genotypes (2.0-3.1 adducts/10(7) bases), however, the average N(2)-Eti-dG level in DNA from ethanol-treated mice was 4.8+/-2.6 adducts/10(7) bases in Aldh2+/+ mice, 7.9+/-1.1 adducts/10(7) bases in Aldh2+/- mice, and 48.6+/-12.0 adducts/10(7) 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.
Nagayoshi
Haruna
H
Osaka Prefectural Institute of Public Health, Osaka 537-0025, Japan.
Matsumoto
Akiko
A
Nishi
Ryuhei
R
Kawamoto
Toshihiro
T
Ichiba
Masayoshi
M
Matsuda
Tomonari
T
D000444:Aldehyde Dehydrogenase / Q000235:genetics*; D000071396:Aldehyde Dehydrogenase, Mitochondrial; D000818:Animals; D002853:Chromatography, Liquid; D018736:DNA Adducts / Q000737:chemistry* / Q000378:metabolism*; D004249:DNA Damage / Q000187:drug effects; D003849:Deoxyguanosine / Q000737:chemistry*; D000431:Ethanol / Q000494:pharmacology*; D005753:Gastric Mucosa / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D015394:Molecular Structure; D013270:Stomach / Q000187:drug effects; D053719:Tandem Mass Spectrometry
D018736:DNA Adducts; D000431:Ethanol; C515029:ALDH2 protein, mouse; D000444:Aldehyde Dehydrogenase; D000071396:Aldehyde Dehydrogenase, Mitochondrial; D003849:Deoxyguanosine