ROLE OF DIETARY SELENIUM ON GENE EXPRESSION, CELL CYCLE AND MOLECULAR MECHANISMS IN CANCER RISK
Location: Grand Forks Human Nutrition Research Center
Title: Noninvasive prediction of prostatic DNA damage by oxidative stress challenge of peripheral blood lymphocytes
| Waters, David - PURDUE UNIVERSITY |
| Shen, Shuren - PURDUE UNIVERSITY |
| Xu, Huiping - PURDUE UNIVERSITY |
| Kengeri, Seema - GP MURPHY CANCER CENTER |
| Colley, Dawn - PURDUE UNIVERSITY |
| Chiang, Emily - PURDUE UNIVERSITY |
| Chen, Yu - PURDUE UNIVERSITY |
| Schlittler, Deborah - PURDUE UNIVERSITY |
| Oteham, Carol - PURDUE UNIVERSITY |
Submitted to: Cancer Epidemiology Biomarkers and Prevention
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: July 15, 2007
Publication Date: September 1, 2007
Citation: Waters, D.J., Shen, S., Xu, H., Kengeri, S.S., Colley, D.M., Chiang, E.C., Chen, Y., Schlittler, D., Oteham, C., Combs, G.F. 2007. Noninvasive prediction of prostatic DNA damage by oxidative stress challenge of peripheral blood lymphocytes. Cancer Epidemiology Biomarkers and Prevention. 16:1906-1910.
Interpretive Summary: Studies were conducted to determine whether a measure of DNA damage could be useful in identifying individuals are highest risk to prostate cancer. These studies were conducted with dogs, which spontaneously develop prostate cancer, specifically assessing the oxidation sensitivity of the DNA from white blood cells obtained from their blood. We found that those cells normally show only low levels of DNA damage, but that they are sensitive to DNA damage induced by oxidative stress, suggesting that the latter may be useful in a biomarker of oxidative cancer sensitivity.
To move closer to the goal of individualized risk prediction for prostate cancer, we used an in vivo canine model to evaluate whether genetic instability, expressed as the susceptibility of peripheral blood lymphocytes (PBLs) to oxidative stress-induced DNA damage, could identify those individuals with the highest prostatic DNA damage. In a randomized feeding trial, 69 elderly beagle dogs received nutritionally adequate or supra-nutritional levels of selenium for seven months; the alkaline Comet assay was used to directly compare the extent of DNA damage in PBLs with prostatic DNA damage in each dog. Using stepwise logistic regression, the sensitivity of PBLs to oxidative stress challenge predicted high prostatic DNA damage. Dogs with PBLs highly sensitive to H2O2 were 7.6 times (95% CI = 1.5-38.3) more likely to have high prostatic DNA damage than those in the H2O2 resistant group; this risk stratification was independent of selenium status. Our data demonstrate that the sensitivity of PBLs to oxidative stress challenge, but not endogenous DNA damage in PBLs, provides a non-invasive surrogate marker for prostatic DNA damage. These findings lend support to the concept that oxidative stress contributes to genotoxic damage and that oxidative stress challenge may stratify men for prostate cancer risk.