BACKGROUND: Chronic inflammation may contribute to cancer risk through the accumulation of specific products as a result of DNA damage. The role of free radical mediated oxidative DNA damage during inflammation was determined in patients with ulcerative colitis by measuring 8-hydroxydeoxyguanosine (8-OHdG). METHODS: Patients with ulcerative colitis were compared according to age, gender, duration and extent of disease, endoscopic and histologic activity, presence or absence of dysplasia/cancer, and biochemical parameters of inflammation. Patients with sporadic colon cancer and irritable bowel syndrome served as controls. Levels of 8-OHdG were assessed by high pressure liquid chromatography with electrochemical detection (mean number of adducts/10(5) dG residues). RESULTS: Patients with ulcerative colitis and dysplasia had significantly higher mucosal 8-OHdG concentrations (P = 0.011). 8-OHdG concentrations were significantly higher in older patients (P = 0.010), patients with long-standing disease (P = 0.015), active endoscopic (P = 0.006) or histologic disease (P = 0.003). Covariance analysis showed significant effect of dysplasia on 8-OHdG levels: values higher than 100 adducts/10(5) dG had a diagnostic value of 80.9% (SE 6.2%). CONCLUSIONS: Oxidative DNA damage accumulates with the duration of the disease in ulcerative colitis reaching maximal increase if dysplastic lesions are found with possible implications for mutagenic and carcinogenic progression.
BACKGROUND: Chronic inflammation may contribute to cancer risk through the accumulation of specific products as a result of DNA damage. The role of free radical mediated oxidative DNA damage during inflammation was determined in patients with ulcerative colitis by measuring 8-hydroxydeoxyguanosine (8-OHdG). METHODS:Patients with ulcerative colitis were compared according to age, gender, duration and extent of disease, endoscopic and histologic activity, presence or absence of dysplasia/cancer, and biochemical parameters of inflammation. Patients with sporadic colon cancer and irritable bowel syndrome served as controls. Levels of 8-OHdG were assessed by high pressure liquid chromatography with electrochemical detection (mean number of adducts/10(5) dG residues). RESULTS:Patients with ulcerative colitis and dysplasia had significantly higher mucosal 8-OHdG concentrations (P = 0.011). 8-OHdG concentrations were significantly higher in older patients (P = 0.010), patients with long-standing disease (P = 0.015), active endoscopic (P = 0.006) or histologic disease (P = 0.003). Covariance analysis showed significant effect of dysplasia on 8-OHdG levels: values higher than 100 adducts/10(5) dG had a diagnostic value of 80.9% (SE 6.2%). CONCLUSIONS: Oxidative DNA damage accumulates with the duration of the disease in ulcerative colitis reaching maximal increase if dysplastic lesions are found with possible implications for mutagenic and carcinogenic progression.
Authors: Helena Shaked; Lorne J Hofseth; Alena Chumanevich; Alexander A Chumanevich; Jin Wang; Yinsheng Wang; Koji Taniguchi; Monica Guma; Steve Shenouda; Hans Clevers; Curtis C Harris; Michael Karin Journal: Proc Natl Acad Sci U S A Date: 2012-08-14 Impact factor: 11.205
Authors: Ioannis E Koutroubakis; Niki Malliaraki; Philippos D Dimoulios; Konstantinos Karmiris; Elias Castanas; Elias A Kouroumalis Journal: Dig Dis Sci Date: 2004-09 Impact factor: 3.199
Authors: Wendy S Garrett; Shivesh Punit; Carey A Gallini; Monia Michaud; Dorothy Zhang; Kirsten S Sigrist; Graham M Lord; Jonathan N Glickman; Laurie H Glimcher Journal: Cancer Cell Date: 2009-09-08 Impact factor: 31.743