Oxidative DNA damage accumulation in gastric carcinogenesis.

Abstract:

BACKGROUND:Gastric carcinogenesis is a multifactorial, multistep process, in which chronic inflammation plays a major role. AIMS:In order to ascertain whether free radical mediated oxidative DNA damage is involved in such a process, concentrations of 8-hydroxydeoxyguanosine (8OHdG), a mutagenic/carcinogenic adduct, and thiobarbituric acid reactive substances (TBARS), as an indirect measure of free radical mediated damage, were determined in biopsy specimens from patients undergoing endoscopy. PATIENTS:Eighty eight patients were divided into histological subgroups as follows: 27 with chronic non-atrophic gastritis, 41 with atrophic gastritis, six with gastric cancer, and 14 unaffected controls. METHODS:Intestinal metaplasia, Helicobacter pylori infection, and disease activity were semiquantitatively scored. 8OHdG concentrations were assessed by HPLC with electrochemical detection, and TBARS concentrations were fluorimetrically assayed. RESULTS:8OHdG concentrations (mean number of adducts/10(5) dG residues) were significantly higher in chronic atrophic gastritis (p = 0.0009). Significantly higher concentrations were also detected in the presence of severe disease activity (p = 0.02), intestinal metaplasia (p = 0.035), and H pylori infection (p = 0.001). TBARS concentrations were also higher in atrophic gastritis, though not significantly so. In a multiple logistic regression analysis, 8OHdG concentrations correlated best with the presence and severity of H pylori infection (r = 0.53, p = 0.002). CONCLUSION:Chronic gastritis is characterised by the accumulation of oxidative DNA damage with mutagenic and carcinogenic potential. H pylori infection is the major determinant for DNA adduct formation.

journal_name

Gut

journal_title

Gut

authors

Farinati F,Cardin R,Degan P,Rugge M,Mario FD,Bonvicini P,Naccarato R

doi

10.1136/gut.42.3.351

subject

Has Abstract

pub_date

1998-03-01 00:00:00

pages

351-6

issue

3

eissn

0017-5749

issn

1468-3288

journal_volume

42

pub_type

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