2232 INCREASED OXIDATIVE STRESS AND DNA DAMAGE IN HIGH-RISK PROSTATE CANCER SUBJECTS (2013)

You have accessJournal of UrologyProstate Cancer: Markers (II)1 Apr 20132232 INCREASED OXIDATIVE STRESS AND DNA DAMAGE IN HIGH-RISK PROSTATE CANCER SUBJECTS Sanjeev Shukla, Janmejai Srivastava, Rajnee Kanwal, Akbar Nawab, Haripaul Sharma, Natarajan Bhaskaran, Claudia Lillibridge, Lee Ponsky, Pingfu Fu, Gregory MacLennan, and Sanjay Gupta Sanjeev ShuklaSanjeev Shukla Cleveland, OH More articles by this author , Janmejai SrivastavaJanmejai Srivastava Cleveland, OH More articles by this author , Rajnee KanwalRajnee Kanwal Cleveland, OH More articles by this author , Akbar NawabAkbar Nawab Cleveland, OH More articles by this author , Haripaul SharmaHaripaul Sharma Cleveland, OH More articles by this author , Natarajan BhaskaranNatarajan Bhaskaran Cleveland, OH More articles by this author , Claudia LillibridgeClaudia Lillibridge Cleveland, OH More articles by this author , Lee PonskyLee Ponsky Cleveland, OH More articles by this author , Pingfu FuPingfu Fu Cleveland, OH More articles by this author , Gregory MacLennanGregory MacLennan Cleveland, OH More articles by this author , and Sanjay GuptaSanjay Gupta Cleveland, OH More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2013.02.2141AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Prostate cancer (PCa) is the most commonly diagnosed cancer among men in the United States. Epidemiological, experimental and clinical studies have implicated chronic inflammation and oxidative stress in the development and progression of PCa. Diet, environmental carcinogens, aging, and other inflammatory diseases cause aberrations in reactive oxygen species (ROS) levels which may play critical role in the initiation and development of PCa. Chronic inflammation results in lipid peroxidation and generation of ROS with the potential to damage DNA. The aim of this study was to assess the oxidative status and antioxidant defense mechanisms in 20 men (54-84 years) with increased risk of developing PCa because of the presence of high-grade prostatic intraepithelial neoplasia (HGPIN) in their prostate biopsies, as compared to 20 healthy men in the same age range whose prostate biopsies showed no evidence of HGPIN. METHODS Plasma PSA levels and the extent of ROS-induced oxidative damage was determined by measuring 8-hydroxydeoxyguanosine (8-OHdG) levels in the DNA, and endogenous antioxidant defense enzymes such as glutathione-s-transferase (GST), glutathione peroxidase (GSH-Px), glutathione reductase (GSH-R), catalase (CAT), superoxide dismutase (SOD) and non-protein thiols, which participate in detoxification processes. RESULTS Total glutathione levels were measured in red blood cells, and plasma levels of GSH-Px, GSH-R, CAT, SOD, and PSA were analyzed and represented as mean, standard error and box plot. The difference of antioxidant enzyme activities between men with and without HGPIN on prostate needle biopsy was examined using T-test. Serum PSA levels were significantly (p<0.0001) higher in men with HGPIN, whereas glutathione (P=0.002) levels were higher in men without HGPIN. Levels of 8-OHdG, an oxidized nucleoside of DNA that is most often detected in the DNA of white blood cells, were significantly (p<0.00001) increased in men with HGPIN. There was no significant difference in levels of GSH-R, GSH-Px, lipid peroxide products, CAT, and SOD in men with or without HGPIN. A significant association in between CAT and GSH-Px activity [r= −0.33 (P=0.04)]; PSA levels and 8-OHdG [r= 0.57 (P=0.002] and between glutathione and 8-OHdG [r= −0.39 (P=0.038] were noted between men with HGPIN and healthy controls using Pearson correlation coefficient. CONCLUSIONS These findings indicate that oxidative stress induces imbalances in oxidant/antioxidant status. Increased 8-OHdG levels may lead to oxidative damage and may thereby play an important role in the development of PCa. © 2013 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 189Issue 4SApril 2013Page: e915 Advertisement Copyright & Permissions© 2013 by American Urological Association Education and Research, Inc.MetricsAuthor Information Sanjeev Shukla Cleveland, OH More articles by this author Janmejai Srivastava Cleveland, OH More articles by this author Rajnee Kanwal Cleveland, OH More articles by this author Akbar Nawab Cleveland, OH More articles by this author Haripaul Sharma Cleveland, OH More articles by this author Natarajan Bhaskaran Cleveland, OH More articles by this author Claudia Lillibridge Cleveland, OH More articles by this author Lee Ponsky Cleveland, OH More articles by this author Pingfu Fu Cleveland, OH More articles by this author Gregory MacLennan Cleveland, OH More articles by this author Sanjay Gupta Cleveland, OH More articles by this author Expand All Advertisement Advertisement PDF DownloadLoading ...