1,N-2-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 ciga rette smoke and automobile exhaust and are also released endogenously by lipid peroxidation. Acrolein- and crotonaldehyde-derived 1,N-2-prop anodeoxyguanosine (Ade and Cdc, respectively) have been detected in th e tissues of carcinogen-treated rodents and as background lesions in D NA from humans and untreated rodents. To determine whether cigarette s moking increases the levels of Ade and CdG, gingival tissue DNA from 1 1 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 previousl y described P-32-postlabeling high-performance liquid chromatography m ethod. The results showed that the mean AdG levels in smokers were sig nificantly higher than those in nonsmokers (1.36 +/- 0.90 mu mol/mol g uanine in smokers versus 0.46 +/- 0.26 mu mol/mol guanine in nonsmoker s; P = 0.003). The mean CdG 1 levels in smokers and nonsmokers were 0. 53 +/- 0.44 and 0.06 +/- 0.07 mu mol/mol guanine, respectively, corres ponding to an 8.8-fold increase for smokers (P = 0.0015). Similar to C dG 1, levels of CdG 2 were increased 5.5-fold in smokers as compared t o nonsmokers, from 0.31 +/- 0.40 to 1.72 +/- 1.26 mu mol/mol guanine ( P = 0.0014). Furthermore, the total levels of cyclic adduct (AdG and C dG) in smokers were 4.4-fold greater than those in nonsmokers (P = 0.0 003), This study shows the detection of the potentially promutagenic 1 ,N-2-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.