N2-Ethyldeoxyguanosine as a Potential Biomarker for Assessing Effects of Alcohol Consumption on DNA

被引：50

作者：

Balbo, Silvia ^{[1
]}

Hashibe, Mia ^{[1
]}

Gundy, Sarolta ^{[2
]}

Brennan, Paul ^{[1
]}

Canova, Cristina ^{[3
]}

Simonato, Lorenzo ^{[3
]}

Merletti, Franco ^{[4
]}

Richiardi, Lorenzo ^{[4
]}

Agudo, Antonio ^{[5
]}

Castellsague, Xavier ^{[5
]}

Znaor, Ariana ^{[6
]}

Talamini, Renato ^{[7
]}

Bencko, Vladimir ^{[8
]}

Holcatova, Ivana ^{[8
]}

Wang, Mingyao ^{[9
]}

Hecht, Stephen S. ^{[9
]}

Boffettal, Paolo ^{[1
]}

机构：

[1] IARC, F-69008 Lyon, France

[2] Natl Inst Oncol, Budapest, Hungary

[3] Univ Padua, Dept Environm Med & Publ Hlth, Padua, Italy

[4] Univ Turin, CeRMS, Canc Epidemiol Unit, Turin, Italy

[5] Inst Catala Oncol, Barcelona, Spain

[6] Croatian Natl Inst Publ Hlth, Zagreb, Croatia

[7] Aviano Canc Ctr, I-33081 Aviano, Italy

[8] Charles Univ Prague, Fac Med 1, Inst Hyg & Epidemiol, Prague, Czech Republic

[9] Univ Minnesota, Ctr Canc, Minneapolis, MN USA

来源：

CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION | 2008年 / 17卷 / 11期

关键词：

D O I：

10.1158/1055-9965.EPI-08-0117

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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)

引用

页码：3026 / 3032

页数：7

共 21 条

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