1,N2-propanodeoxyguanosine adducts: potential new biomarkers of smoking-induced DNA damage in human oral tissue.
Highly DNA-reactive alpha,beta-unsaturated aldehydes such as acrolein and crotonaldehyde are common environmental pollutants present in cigarette smoke and automobile exhaust and are also released endogenously by lipid peroxidation. Acrolein- and crotonaldehyde-derived 1,N2-propanodeoxyguanosine (AdG and CdG, respectively) have been detected in the tissues of carcinogen-treated rodents and as background lesions in DNA from humans and untreated rodents. To determine whether cigarette smoking increases the levels of AdG and CdG, gingival tissue DNA from 11 smokers (4 males and 7 females; 30-58 years old) and 12 nonsmokers (8 males and 4 females; 21-66 years old) was analyzed using a previously described 32P-postlabeling high-performance liquid chromatography method. The results showed that the mean AdG levels in smokers were significantly higher than those in nonsmokers (1.36 +/- 0.90 micromol/mol guanine in smokers versus 0.46 +/- 0.26 micromol/mol guanine in nonsmokers; P = 0.003). The mean CdG 1 levels in smokers and nonsmokers were 0.53 +/- 0.44 and 0.06 +/- 0.07 micromol/mol guanine, respectively, corresponding to an 8.8-fold increase for smokers (P = 0.0015). Similar to CdG 1, levels of CdG 2 were increased 5.5-fold in smokers as compared to nonsmokers, from 0.31 +/- 0.40 to 1.72 +/- 1.26 micromol/mol guanine (P = 0.0014). Furthermore, the total levels of cyclic adduct (AdG and CdG) in smokers were 4.4-fold greater than those in nonsmokers (P = 0.0003). This study shows the detection of the potentially promutagenic 1,N2-propanoguanine adducts in human oral tissues and demonstrates for the first time an increase of structurally identified adducts in oral tissue DNA by cigarette smoking.
Nath
R G
RG
American Health Foundation, Division of Carcinogenesis and Molecular Epidemiology, Valhalla, New York 10595, USA.
Ocando
J E
JE
Guttenplan
J B
JB
Chung
F L
FL
D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000032:analysis; D002851:Chromatography, High Pressure Liquid; D018736:DNA Adducts / Q000032:analysis; D004249:DNA Damage; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000032:analysis; D005260:Female; D005881:Gingiva / Q000737:chemistry*; D006801:Humans; D008297:Male; D008875:Middle Aged; D012907:Smoking / Q000009:adverse effects*
D015415:Biomarkers; D018736:DNA Adducts; C060934:1,N(2)-propanodeoxyguanosine; D003849:Deoxyguanosine