title: Time course of DNA adduct formation in peripheral blood granulocytes and lymphocytes after drinking alcohol.
abstract: Alcohol consumption is an established risk factor for cancers of the head and neck, colorectum, liver and female breast. Acetaldehyde, the primary metabolite of ethanol, is suspected to play a major role in alcohol-related carcinogenesis. Acetaldehyde binds to DNA resulting in formation of adducts. DNA adducts are involved in mutagenesis and carcinogenesis. N (2)-Ethylidenedeoxyguanosine (N (2)-ethylidene-dGuo) is the major adduct formed in this reaction. Studies have shown an association between alcohol drinking and levels of this DNA adduct, suggesting its potential use as a biomarker for studying alcohol-related carcinogenesis. However, there are no reports on the kinetics of formation and repair of N (2)-ethylidene-dGuo after alcohol consumption. Therefore, we investigated levels of N (2)-ethylidene-dGuo in DNA from human peripheral blood cells at several time points after consumption of increasing doses of alcohol. Ten healthy non-smokers were recruited and asked to abstain from alcohol consumption except for the study doses. The subjects were given measured doses of alcohol once a week for 3 weeks, targeting increasing blood alcohol levels. Blood was collected at several time points before and after each dose, DNA was isolated from granulocytes and lymphocytes and N (2)-ethylidene-dGuo was quantified as its NaBH(3)CN reduction product N ( 2 )-ethyldeoxyguanosine by liquid chromatography-electrospray ionisation-tandem mass spectrometry. Significant increases in N (2)-ethylidene-dGuo were observed after all doses and in both cell types. However, there was substantial intraindividual variability, indicating that there are other important sources of this adduct in peripheral blood DNA. Further studies are needed to better understand the origins of N (2)-ethylidene-dGuo in blood cells, the exposures it reflects, and thus its potential use as a marker of alcohol's genotoxic effects.
authors.affiliation: Masonic Cancer Center, University of Minnesota, MMC 806, 420 Delaware Street SE, Minneapolis, MN 55455, USA. balbo006@umn.edu
authors.forename: Silvia
authors.initials: S
authors.lastname: Balbo
authors.forename: Lei
authors.initials: L
authors.lastname: Meng
authors.forename: Robin L
authors.initials: RL
authors.lastname: Bliss
authors.forename: Joni A
authors.initials: JA
authors.lastname: Jensen
authors.forename: Dorothy K
authors.initials: DK
authors.lastname: Hatsukami
authors.forename: Stephen S
authors.initials: SS
authors.lastname: Hecht
mesh_terms: D000328:Adult; D000428:Alcohol Drinking; D015415:Biomarkers / Q000097:blood*; D002851:Chromatography, High Pressure Liquid; D002853:Chromatography, Liquid; D018736:DNA Adducts / Q000378:metabolism*; D004249:DNA Damage / Q000187:drug effects; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000378:metabolism; D005260:Female; D006098:Granulocytes / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D008214:Lymphocytes / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D021241:Spectrometry, Mass, Electrospray Ionization; D013997:Time Factors; D055815:Young Adult
chemical_list: D015415:Biomarkers; D018736:DNA Adducts; C492934:N2-ethyl-2'-deoxyguanosine; D003849:Deoxyguanosine