Presentation Abstract

Abstract Number: 4700
Presentation Title: Acrolein-deoxyguanosine DNA adduct formation and lung cancer
Presentation Time: Tuesday, Apr 20, 2010, 2:00 PM - 5:00 PM
Location: Exhibit Hall A-C, Poster Section 33
Poster Section: 33
Poster Board Number: 9
Author Block: Yu Hu1, William Rom2, Harvey I. Pass3, Simon D Spivack4, Moon-shong Tang5. 1Department of Environmental Medicine, New York University, Tuxedo, NY; 2Department of Environmental Medicine, Department of Medicine, New York University, New York, NY; 3Division of Thoracic Surgery and Thoracic Oncology, New York University, New York, NY; 4Albert Einstein College of Medicine, Bronx, NY; 5Department of Environmental Medicine, Department of Medicine, New York University, Tuxedo, NY
Abstract Body: Cigarette smoke (CS) contains 1,000-10,000 fold more acrolein (Acr) and crotonaldehyde (Crot) than polycyclic aromatic hydrocarbons (PAHs). These aldehydes can induce propanoldeoxyguanosine (propanol-dG) DNA adducts formation in cultured normal human lung epithelial cells. Previously, we have found that the distribution of Acr-dG in the p53 gene coincides with the lung cancer p53 mutational spectrum of cigarette smokers, and that Acr-dG induces similar level of G to T transversion and G to A transition mutations as in lung cancer of cigarette smokers. Hence, we have proposed that Acr is a major etiological agent of CS related lung cancer. We developed a 32P-postlabelling method in combination with 2D TLC/HPLC method to quantify propanol-dG formation in human lung tissue. To date we have determined Acr-dG and Crot-dG in the lung tissue of cigarette smokers (n=27) and nonsmokers (n=25) with lung cancer. We found that 1) both α- and γ-Acr-dG are formed in lung tissues of smokers and nonsmokers, and the level of these two types of adduct in lung tissue varies from 10-4,510, and 0-1,900 fmole/μmole, respectively; and 2) smokers appear to have a higher level of γ-Acr-dG than nonsmokers although the differences have not reached statistical significance (p=0.1854); 3) the level of Crot-dG in smokers is significant higher than that in nonsmokers (p=0.0279). These results indicate a substantial amount of Acr-dG and Crot-dG formed in lung tissue of lung cancer.
Key words: α, β-unsaturated aldehydes, cigarette smoking, DNA adducts, lung cancer.