Oxidative DNA damage in the mucosa of ulcerative colitis increases with disease duration and dysplasia.
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.
D'Incà
Renata
R
Department of Surgical and Gastroenterological Sciences, University of Padua, Italy. dinca@unipd.it
Cardin
Romilda
R
Benazzato
Luca
L
Angriman
Imerio
I
Martines
Diego
D
Sturniolo
Giacomo Carlo
GC
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D003093:Colitis, Ulcerative / Q000235:genetics* / Q000473:pathology; D003110:Colonic Neoplasms / Q000235:genetics* / Q000473:pathology; D004249:DNA Damage; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000032:analysis*; D005260:Female; D006801:Humans; D007413:Intestinal Mucosa / Q000737:chemistry / Q000473:pathology; D008297:Male; D008875:Middle Aged; D012720:Severity of Illness Index
D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine