Aims

To support the free and open dissemination of research findings and information on alcoholism and alcohol-related problems. To encourage open access to peer-reviewed articles free for all to view.

For full versions of posted research articles readers are encouraged to email requests for "electronic reprints" (text file, PDF files, FAX copies) to the corresponding or lead author, who is highlighted in the posting.

___________________________________________

Saturday, November 8, 2008

N2-Ethyldeoxyguanosine as a Potential Biomarker for Assessing Effects of Alcohol Consumption on DNA
Cancer Epidemiology Biomarkers & Prevention
17, 3026-3032, November 1, 2008


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, N2-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 N2-ethyldeoxyguanosine (N2-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. N2-ethyl-dGuo was detected in all DNA samples.

After adjusting for potential confounders, in the first study, drinkers showed a higher level of N2-ethyl-dGuo (5,270 ± 8,770 fmol/µmol dGuo) compared with nondrinkers (2,690 ± 3040 fmol/µmol 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 N2-ethyl-dGuo in small-volume blood samples and are consistent with the hypothesis that ethanol contributes to carcinogenesis through DNA adducts formation.

Read Full Abstract

Request Reprint E-Mail: boffetta@iarc.fr
___________________________________________________