Abstract 9: Oxidative stress and antioxidant status in high-risk prostate cancer subjects.

Abstract

Abstract Prostate cancer 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 prostate cancer. Diet, environmental carcinogens, aging, and other inflammatory diseases cause aberration in reactive oxygen species (ROS) which may play critical roles in the development and progression of prostate cancer. Chronic inflammation results in lipid peroxidation and generation of highly reactive products with the potential to damage DNA. The extent of ROS-induced oxidative damage can be determined by measuring reductions in levels of 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. The aim of this study was to assess the oxidative status and antioxidant defense mechanisms in 20 men, 54-84 years of age, with increased risk of developing prostate cancer 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. Total glutathione levels were measured in red blood cells, and plasma levels of GSH-Px, GSH-R, CAT, SOD, and PSA were analyzed. Data obtained after analysis was represented as mean, standard error and box plot. 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-hydroxydeoxyguanosine (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. 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 prostate cancer. Citation Format: Sanjeev Shukla, Janmejai K. Srivastava, Rajnee Kanwal, Akbar Nawab, Haripaul Sharma, Natarajan Bhaskaran, Claudia Lillibridge, Lee E. Ponsky, Pingfu Fu, Gregory T. MacLennan, Sanjay Gupta. Oxidative stress and antioxidant status in high-risk prostate cancer subjects. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 9. doi:10.1158/1538-7445.AM2013-9