Pancreatic cancer represents a leading cause of cancer-related mortality, with only limited (<5 years) survival rate. Cigarette smoking has been implicated in the development of pancreatic cancer. Because of the high mortality rate, it is necessary that early biomarkers be developed before the onset of pathological changes. In this study, we analyzed highly lipophilic adducts in the pancreas DNA of non-smokers (n=7.) and smokers (n=8). Tissues were obtained from the U.S. Cooperative Tissue Network, and the isolated DNAs were analyzed by nuclease P1-mediated 32P-postlabeling/TLC. When chromatographed in standard high-salt, high-urea solvents, adducts migrated in the form of diagonal radioactive zones in both non-smokers and smokers; however, the adduct load was significantly (p=0.031) higher in smokers (231±38 adducts/109 nucleotides, mean±SE) compared with non-smokers (94±42 adducts/109 nucleotides). To determine the chemical nature of the adducts, selected smoker DNA samples were analyzed together with a mixture of reference DNA adducted with the anti-diolepoxides of benzo[a]pyrene, dibenz[a,h]anthracene and benz[a]anthracene. In the urea-based solvents, the pancreas DNA adducts co-migrated with the reference adducts. However, the pancreas DNA adducts were well resolved from the reference adducts in dilute ammonium hydroxide-based solvent. The assay conditions used were able to detect adducts at low levels (1 adduct/108-9 nucleotides). These results indicate that the smoke-associated DNA adducts are unrelated to typical polyaromatic hydrocarbons present in cigarette smoke. Furthermore, reference DNA adducted with formaldehyde and acetaldehyde showed adducts migrating in typical diagonal radioactive zones in the urea-based solvents, but not in ammonium hydroxide-based solvent, suggesting that adducts migrating in the form of diagonal radioactive zones can also result from compounds other than polyaromatic hydrocarbons. In conclusion, our data show elevated levels of lipophilic adducts in the pancreas DNA of smokers compared with non-smokers, but the adducts are unrelated to typical polyaromatic hydrocarbons, and further suggest that other smoke constituents such as formaldehydes, acetaldehyde, butadiene, etc. may contribute to the DNA damage.
[Proc Amer Assoc Cancer Res, Volume 47, 2006]