8-hydroxy-2--deoxyguanosine and Cholecystitis

Gallbladder cancer (GBC) is a fatal condition with dismal prognosis and aggressive local invasiveness; and with uncharacterised molecular pathology relating to non-specific therapeutic modalities. Given the importance of oxidative stress in chronic diseases and carcinogenesis, and the lacunae in literature regarding its role in gallbladder diseases, this study aimed to study the involvement of oxidative stress and deregulation in the base excision repair (BER) pathway in the pathogenesis of gallbladder diseases including GBC. This study involved patients from the North-East Indian population, where the numbers of reported cases are increasing rapidly and alarmingly. Oxidative stress, based on 8-OH-dG levels, was found to be significantly higher in gallbladder anomalies (cholelithiasis [CL] and cholecystitis [CS]) and GBC at the plasma and DNA level, and was associated with GBC severity. The expressions of key BER pathway genes were downregulated in gallbladder anomalies and GBC compared to controls, and in GBC compared to both non-neoplastic controls and gallbladder anomalies. Expression of

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adolescent; Adult; Aged; Case-Control Studies; Cholecystitis; Cholelithiasis; DNA Glycosylases; DNA Methylation; DNA Repair; Female; Gallbladder; Gallbladder Neoplasms; Gene Expression Regulation, Neoplastic; Genetic Predisposition to Disease; Humans; India; Male; Middle Aged; Neoplasm Invasiveness; Oxidative Stress; Polymorphism, Single Nucleotide; Prognosis; Promoter Regions, Genetic; Severity of Illness Index; Signal Transduction; X-ray Repair Cross Complementing Protein 1

Recent studies suggest that oxidative DNA damage induced during chronic inflammation may play a role in carcinogenesis in some organs. Although gallbladder carcinomas are frequently observed with a background of chronic cholecystitis, little is known about oxidative DNA damage in chronic cholecystitis. The aims of this study were to investigate the expression of 8-hydroxydeoxyguanosine (8-OHdG), a biomarker of oxidative DNA damage, in normal and chronically inflamed human gallbladder mucosa and compare its expression with clinicopathological findings.. 8-OHdG expression was immunohistochemically examined using a monoclonal antibody against 8-OHdG in human gallbladder specimens. In normal gallbladder (n=5), no 8-OHdG expression was observed. In contrast, nuclear expression of 8-OHdG was detected in 28 of 31cases (90.3%) in gallbladder epithelial cells with chronic cholecystitis. The positive cells were predominantly observed in the areas of active inflammation with prominent cell infiltration. Quantitative analysis revealed that the number of 8-OHdG+ cells (labelling index) significantly (rs=0.671, P < 0.05) correlated with the degree of the activity of mucosal inflammation, while gender, age, and the presence of gallstones did not influence the index.. Oxidative DNA damage is common in chronic cholecystitis, suggesting a possible link between chronic inflammation and gallbladder carcinogenesis.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Antibody Specificity; Biomarkers; Cholecystitis; Chronic Disease; Deoxyguanosine; DNA Damage; Female; Gallbladder; Humans; Immunohistochemistry; Male; Middle Aged