title: Reactive nitrogen species mediate DNA damage in Helicobacter pylori-infected gastric mucosa.
abstract: 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 with Helicobacter pylori. 8-OH-deoxy guanosine (8-OHdG) and 8-nitroguanine (8-NG) are markers for ROS- and RNS-mediated 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 how H. pylori infection 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) with H. pylori-positive gastritis and 19 patients (11 men and 8 women) exhibiting successful H. pylori eradication. 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. Successful H. pylori eradication resulted in a significant reduction of chronic inflammatory cell infiltration and neutrophilic activity. Mean 8-OHdG production was lower after H. pylori eradication 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 pylori infection 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 for H. pylori-induced DNA damage in gastric mucosa.
authors.affiliation: Department of Gastroenterology and Hepatology, Division of Clinical Medicine and Biochemical Sciences, Mie University Graduate School of Medicine, Mie, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Katsurahara
authors.forename: Yoshinao
authors.initials: Y
authors.lastname: Kobayashi
authors.forename: Motoh
authors.initials: M
authors.lastname: Iwasa
authors.forename: Ning
authors.initials: N
authors.lastname: Ma
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Inoue
authors.forename: Naoki
authors.initials: N
authors.lastname: Fujita
authors.forename: Kyosuke
authors.initials: K
authors.lastname: Tanaka
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Horiki
authors.forename: Esteban C
authors.initials: EC
authors.lastname: Gabazza
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Takei
mesh_terms: D000328:Adult; D000368:Aged; D004249:DNA Damage; D005260:Female; D005753:Gastric Mucosa / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology; D006147:Guanine / Q000031:analogs & derivatives / Q000378:metabolism; D016481:Helicobacter Infections / Q000235:genetics* / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology; D016480:Helicobacter pylori / Q000276:immunology / Q000502:physiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D026361:Reactive Nitrogen Species / Q000378:metabolism*; D055815:Young Adult
chemical_list: C095838:8-nitroguanine; D026361:Reactive Nitrogen Species; D006147:Guanine