Increased formation of gastric N2-ethylidene-2′-deoxyguanosine DNA adducts in aldehyde dehydrogenase-2 knockout mice treated with ethanol
Increased formation of gastric N2-ethylidene-2′-deoxyguanosine DNA adducts in aldehyde dehydrogenase-2 knockout mice treated with ethanol
复制标题
DOI：
10.1016/j.mrgentox.2008.11.009
复制
发表时间：
2009-02-19
影响因子：
1.9
通讯作者：
Matsuda, Tomonari
中科院分区：
文献类型：
--
作者：
Nagayoshi, Haruna;Matsumoto, Akiko;Matsuda, Tomonari
我们分析了乙醛脱氢酶 (Aldh)-2 敲除小鼠胃 DNA 中的乙醛衍生 DNA 加合物 N-2-亚乙基-2'-脱氧鸟苷 (N-2-Eti-dG)，这些小鼠喂食酒精，以确定饮酒和 Aldh2 基因型对胃 DNA 损伤水平的影响。 Aldh2-活性(+/+)。杂合子(+/-)和基因敲除(-/-)小鼠被喂食20%乙醇5周。采用液相色谱串联质谱法测定胃内N-2-Eti-dG的含量。未经处理的小鼠 DNA 中的平均 N-2-Eti-dG 水平在 Aldh2 基因型之间没有显着差异（2.0-3.1 加合物/10(7) 个碱基），然而，乙醇处理的小鼠 DNA 中的平均 N-2-Eti-dG 水平在 Aldh2+/+ 小鼠中为 4.8 +/- 2.6 加合物/10(7) 个碱基，7.9 +/- 1.1 Aldh2+/- 小鼠中分别为 48.6 +/- 12.0 加合物/10(7) 个碱基，Aldh2-/- 小鼠中分别为 48.6 +/- 12.0 个加合物/10(7) 个碱基。我们的数据清楚地表明，饮酒会导致胃部 DNA 损伤，在该实验动物模型中，这种损伤与 Aldh2 基因型相关。这一结果表明，大量饮酒和Aldh2缺乏可能是胃癌的危险因素。 (C) 2008 Elsevier B.V. 保留所有权利。
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. (C) 2008 Elsevier B.V. All rights reserved.