期刊
CHEMICAL RESEARCH IN TOXICOLOGY
卷 20, 期 1, 页码 108-113出版社
AMER CHEMICAL SOC
DOI: 10.1021/tx060232x
关键词
-
资金
- NCI NIH HHS [CA-77598, P30 CA077598] Funding Source: Medline
- NIEHS NIH HHS [ES-11297, R01 ES011297, R01 ES011297-01] Funding Source: Medline
Acetaldehyde is one of the most prevalent carcinogens in cigarette smoke. It is also a major metabolite of ethanol and is found widely in the human diet and environment. Acetaldehyde DNA adducts are critical for its carcinogenic properties. The role of acetaldehyde DNA adducts in human cancer related to tobacco and alcohol exposure could be investigated with a suitable biomarker. Therefore, in this study, we have developed a method for analysis of the major DNA adduct of acetaldehyde, N-2-ethylidene-dGuo (1), in human leukocyte DNA. Leukocyte DNA was subjected to enzyme hydrolysis in the presence of NaBH3CN, which converts adduct 1 to N-2-ethyl-dGuo (2). [N-15(5)]N-2-ethyl-dGuo was used as the internal standard. After solid-phase extraction, N-2-ethyl-dGuo was quantified by LC-ESI-MS/MS-SRM. The method was sensitive, accurate, and precise, and applicable to low microgram amounts of DNA. It was applied to investigate the effect of smoking cessation on levels of adduct 1, measured as adduct 2. Twenty-five smokers who were only light drinkers were eligible for the study. Levels of adduct 2 were quantified at two baseline time points separated by one week and again after four weeks of abstinence from smoking and alcohol consumption. The mean (+/- S.D.) levels of adduct 2 measured in the leukocytes of the smokers were 1310 +/- 1720 (range 124-7700) and 1120 +/- 1140 (range 138-5760) fmol/mu mol dGuo at the two baseline points and 705 +/- 438 (range 111-1530) fmol/mu mol dGuo after 4 weeks of cessation. The median level of adduct 2 decreased significantly by 28% upon quitting smoking (P = 0.02). These results demonstrate that the major acetaldehyde DNA adduct can be reliably quantified by MS/MS methods in human leukocyte DNA and that cigarette smoking has a modest but significant effect on its levels.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据