Oxidative DNA damage accumulation in gastric carcinogenesis

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 (80HdG), a mutagenic/carcinogenic adduct, and thiobarbituric acid reactive substances (TEARS), 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. 80HdG concentrations were assessed by HPLC with electrochemical detection, and TEARS concentrations were fluorimetrically assayed. Results-80HdG 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). TEARS concentrations were also higher in atrophic gastritis, though not significantly so. In a multiple logistic regression analysis, 80HdG concentrations correlated best with the presence and severity of H pylori infection (r=0.53, p=0.002). Conclusions-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.