期刊
CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
卷 17, 期 11, 页码 3026-3032出版社
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/1055-9965.EPI-08-0117
关键词
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资金
- European Commission's 5th Framework Program [QLK1-2001-00182]
- Environmental Cancer Risk, Nutrition and Individual Susceptibility, a network of excellence operating within the European Union 6th Framework Program [513943]
- U.S. National Institute of Environmental Health Sciences [ES-011297]
- Hungarian National [NKFP/1B/020/04]
- Compagnia San Paolo
- Italian Association for Cancer Research
- Region Piedmont
Head and neck cancers are causally related to alcohol consumption, but the underlying mechanisms are unclear. Ethanol is metabolized to acetaldehyde, an experimental carcinogen. Quantitation of the major DNA adduct of acetaldehyde, N-2-ethylidenedeoxyguanosine, in human tissues could help to elucidate the mechanism of alcohol carcinogenicity. We applied a quantitative method for the analysis of this adduct, measured as the NaBH3CN reduction product N-2-ethyldeoxyguanosine (N-2-ethyl-dGuo) by liquid chromatography-electrospray ionization-tandem mass spectrometry-selected reaction monitoring, on DNA (0.04 +/- 0.03 mg) isolated from blood collected from control subjects recruited from two studies conducted in different areas of Europe between 1999 and 2005. The group selected from the first study (n = 127) included alcohol drinkers and abstainers while the group from the second study (n = 50) included only heavy drinkers. N-2-ethyl-dGuo was detected in all DNA samples. After adjusting for potential confounders, in the first study, drinkers showed a higher level of N-2-ethyl-dGuo (5,270 +/- 8,770 fmol/mu mol dGuo) compared with nondrinkers (2,690 +/- 3040 fmol/mu mol dGuo; P = 0.04). A significant trend according to dose was observed in both studies (P = 0.02 and 0.04, respectively). Taking into account the amount of alcohol consumption, adduct levels were higher in younger compared with older subjects (P = 0.01), whereas no differences were observed comparing men with women. These results show the feasibility of quantifying N-2-ethyl-dGuo in small-volume blood samples and are consistent with the hypothesis that ethanol contributes to carcinogenesis through DNA adducts formation. (Cancer Epidemiol Biomarkers Prev 2008;17(11):3026-32)
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