Noninvasive prediction of prostatic DNA damage by oxidative stress challenge of peripheral blood lymphocytes

David J. Waters, Shuren Shen, Huiping Xu, Seema S. Kengeri, Dawn M. Cooley, Emily C. Chiang, Yu Chen, Deborah Schlittler, Carol Oteham, Gerald F. Combs, Lawrence T. Glickman, J. Steven Morris, David G. Bostwick

Research output: Contribution to journalArticle

20 Scopus citations

Abstract

To move closer to the goal of individualized risk prediction for prostate cancer, we used an in vivo canine model to evaluate whether the susceptibility of peripheral blood lymphocytes (PBLs) to oxidative stress-induced DNA damage could identify those individuals with the highest prostatic DNA damage. This hypothesis was tested in a population of 69 elderly male beagle dogs after they had completed a 7-month randomized feeding trial to achieve the broad range of dietary selenium status observed in U.S. men. 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 with hydrogen peroxide (H2O2) predicted dogs in the highest tertile of prostatic DNA damage. Dogs with PBLs highly sensitive to H2O2 were 7.6 times [95% confidence interval (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 observed in multivariate analysis that considered other factors that might influence DNA damage, such as age, toenail selenium concentration, and serum testosterone concentration. Our data show that the sensitivity of PBLs to oxidative stress challenge, but not endogenous DNA damage in PBLs, provides a noninvasive 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.

Original languageEnglish (US)
Pages (from-to)1906-1910
Number of pages5
JournalCancer Epidemiology Biomarkers and Prevention
Volume16
Issue number9
DOIs
StatePublished - Sep 1 2007
Externally publishedYes

ASJC Scopus subject areas

  • Epidemiology
  • Oncology

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    Waters, D. J., Shen, S., Xu, H., Kengeri, S. S., Cooley, D. M., Chiang, E. C., Chen, Y., Schlittler, D., Oteham, C., Combs, G. F., Glickman, L. T., Morris, J. S., & Bostwick, D. G. (2007). Noninvasive prediction of prostatic DNA damage by oxidative stress challenge of peripheral blood lymphocytes. Cancer Epidemiology Biomarkers and Prevention, 16(9), 1906-1910. https://doi.org/10.1158/1055-9965.EPI-07-0034