Reactive Nitrogen Species Mediate DNA Damage inHelicobacter pylori-Infected Gastric Mucosa

Background:Reactive oxygen species (ROS) and reactive nitrogen species (RNS) can play an important role in cellular injury and carcinogenesis of gastric epithelial cells infected withHelicobacter pylori. 8-OH-deoxy guanosine (8-OHdG) and 8-nitroguanine (8-NG) are markers for ROS- and RNSmediated DNA oxidation, respectively. In this study, RNS-mediated DNA damage in gastric mucosa was observed directly using a newly developed antibody to 8-NG to clarify howH. pyloriinfection causes nitrative DNA damage to gastric epithelial cells. Methods:Immunohistochemistry with anti-8-OHdG and anti-8-NG antibodies was performed on gastric tissue samples from 45 patients (25 men and 20 women) withH. pylori-positive gastritis and 19 patients (11 men and 8 women) exhibiting successfulH. pylorieradication. Histologic factors for gastric mucosal inflammation were graded according to the guidelines of the Updated Sydney system. Results:In corpus mucosa, 8-OHdG and 8-NG production were significantly associated with the degree of glandular atrophy, infiltration of chronic inflammatory cells and intestinal metaplasia in the glandular epithelial cells. SuccessfulH. pylorieradication resulted in a significant reduction of chronic inflammatory cell infiltration and neutrophilic activity. Mean 8-OHdG production was lower afterH. pylorieradication in both corpus and antral mucosa (p= .022 and .049, respectively). However, the reduction in 8-NG exhibited was more pronounced than the reduction of 8-OhdG (p= .004 and .007, respectively). Conclusions:Helicobacter pyloriinfection can induce inflammatory cells infiltration, which evokes DNA damage of gastric epithelial cells through ROS and RNS production. 8-NG might be a more sensitive biomarker than 8-OHdG forH. pylori-induced DNA damage in gastric mucosa. Helicobacter ISSN 1523-5378