OXIDATIVE DNA-DAMAGE ACCUMULATION IN GASTRIC CARCINOGENESIS

Background-Gastric carcinogenesis is a multifactorial, multistep proce ss, in which chronic inflammation plays a major role. Aims-In order to ascertain whether free radical mediated oxidative DNA damage is invol ved in such a process, concentrations of 8-hydroxydeoxyguanosine (80Hd G), a mutagenic/carcinogenic adduct, and thiobarbituric acid reactive substances (TEARS), as an indirect measure of free radical mediated da mage, were determined in biopsy specimens from patients undergoing end oscopy. 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 control s. Methods-Intestinal metaplasia, Helicobacter pylori infection, and d isease activity were semiquantitatively scored. 80HdG concentrations w ere assessed by HPLC with electrochemical detection, and TEARS concent rations were fluorimetrically assayed. Results-80HdG concentrations (m ean number of adducts/10(5) dG residues) were significantly higher in chronic atrophic gastritis (p=0.0009). Significantly higher concentrat ions were also detected in the presence of severe disease activity (p= 0.02), intestinal metaplasia (p=0.035), and H pylori infection (p=0.00 1). TEARS concentrations were also higher in atrophic gastritis, thoug h not significantly so. In a multiple logistic regression analysis, 80 HdG 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 mutagen ic and carcinogenic potential. H pylori infection is the major determi nant for DNA adduct formation.