Presentation Abstract

Abstract Number: 4903
Presentation Title: Oxidative DNA damage and its relationship with GSTP1 methylation in prostate cancer
Presentation Time: Wednesday, Apr 21, 2010, 8:00 AM -11:00 AM
Location: Exhibit Hall A-C, Poster Section 3
Poster Section: 3
Poster Board Number: 13
Author Block: Rajnee Fnu, Haripaul Sharma, Sanjay Gupta. Case Western Reserve University, Cleveland, OH
Abstract Body: Prostate cancer is the most common cancer diagnosed in men and is the second leading cause of cancer-related death in the United States. The risk factor for prostate cancer includes both genetic and epigenetic modifications. Growing evidence suggests that epigenetic mechanisms such as DNA methylation affect gene expression in tissue-specific manner. The most frequent epigenetic alteration observed in human prostate cancer is hypermethylation of gluthathione-S-transferase-pi class (GSTP1) in the promoter region which causes loss or its decrease expression. Inactivation of GSTP1 renders prostate epithelial cells vulnerable to oxidative DNA damage from both oxidants and electrophile carcinogens to acquire relevant genetic alteration and neoplastic transformation. Extensive observations suggest that reactive oxygen species may cause accumulated DNA damage which might contribute to increased incidence of prostate cancer. However, the role of GSTP1 and its correlation with DNA damage has not been studied. Based on the assumption that DNA damage is prevalent in cancer cells compared to nontumorous tissue, we took a panel of 24 human prostate specimens obtained after surgery which comprised of matched primary tumor and adjacent nontumorous (benign) prostate tissues. Oxidative DNA damage was measured by 8-hydroxy-2’-deoxyguanosine (8-OHdG) levels through highly sensitive and quantitative ELISA assay. GSTP1 methylation was determined by methyl-specific PCR and 5-methylcytosine estimation was performed by HPLC analysis. The 8-OHdG levels were higher in cancer specimen compared to their benign counterparts. The 8-OHdG levels in DNA of prostate cancer tissues ranged from 0.151 to 0.616ng/μg DNA, whereas the levels in benign tissue range from 0.149 to 0.318ng/μg DNA, respectively. The increase in 8-OHdG levels correlate with GSTP1 methylation which was higher in cancer specimens compared to the benign counterparts. Furthermore, levels of 5-methylcytosine were higher in tumor specimens compared to benign tissue. Taken together, our studies suggest that there is a link between GSTP1 methylation and DNA damage which correlates to epigenetic modification in prostate cancer. Our results are in agreement with the prediction that positive relationship occur between GSTP1 inactivation and DNA damage in prostate cancer.