Detection of acetaldehyde derived N2-ethyl-2¡ä-deoxyguanosine in human leukocyte DNA following alcohol consumption
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文摘
Epidemiological studies have shown an association between alcohol (ethanol) consumption and increased cancer risk. The effect of alcohol consumption on the levels and persistence of N2-ethylidene-2¡ä-deoxyguanosine (N2-ethylidene-dG) formed by acetaldehyde, the oxidative metabolite of ethanol, in human leukocyte DNA was investigated. DNA was isolated from venous blood samples obtained from 30 male non-smoking individuals before consumption of alcohol (0 h) and subsequently at 3-5 h following the consumption of 150 mL of vodka (containing 42 % pure ethanol). Additional samples were collected 24 h and 48 h post-alcohol consumption. The levels of N2-ethyl-2¡ä-deoxyguanosine (N2-ethyl-dG) in the DNA were determined following reduction of N2-ethylidene-dG with sodium cyanoborohydride using a liquid chromatography-tandem mass spectrometry selected reaction monitoring method. A slight time-dependent trend showing an increase and decrease in the levels of N2-ethyl-dG was observed following consumption of alcohol compared to time 0 h, however, the differences were not statistically significant. The average levels of N2-ethyl-dG observed at 0 h, 3-5 h, 24 h and 48 h time points following ingestion of alcohol were 34.6 ¡À 21.9, 35.1 ¡À 21.0, 36.8 ¡À 20.7 and 35.6 ¡À 21.1 per 108 2¡ä-deoxynucleosides, respectively. In conclusion, alcohol consumption that could be encountered under social drinking conditions, does not significantly alter the levels of the acetaldehyde derived DNA adduct, N2-ethyl-dG in human leukocyte DNA from healthy individuals.
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