BACKGROUND: Helicobacter pylori infection is associated with gastric cancer. Study with the Big Blue mouse model has reported a mutagenic effect associated with the H. pylori infection, as a result in part of oxidative DNA damage. The present work investigates the consequences of a deficiency in the OGG1 DNA glycosylase, responsible for the excision of 8-oxo guanine, on the inflammatory and genotoxic host response to the infection. MATERIALS AND METHODS: Big Blue Ogg1-/- C57BL/6 mice were orally inoculated with H. pylori strain SS1 or vehicle only, and sacrificed after 1, 3, or 6 months. The serologic response, histologic lesions, mutant frequency, and spectra of mutations were assessed in the stomach and compared to what observed in the wild-type (Wt) context. RESULTS: Inflammatory lesions induced in the gastric mucosa of H. pylori-infected mice, corresponding to a moderate gastritis, were less severe in Ogg1-/- than in Wt Big Blue mice. Analysis of antimicrobial humoral immunity exhibited a lower IgG2a serum level (Th1 response) after 6 months of infection in Ogg1-/- than in the Wt mice. In these conditions, the H. pylori-SS1 infection in the Ogg1-/- mice did not induce a mutagenic effect at the gastric epithelial cells level, either after 3 or 6 months. CONCLUSIONS: The inactivation of the OGG1 DNA glycosylase in mouse leads to less severe inflammatory lesions and abolished the mutagenic effect at the gastric epithelial cells level, induced by the H. pylori infection. These data suggest for the OGG1deficiency a protective role against inflammation and genotoxicity associated to the H. pylori infection.
BACKGROUND: Helicobacter pylori infection is associated with gastric cancer. Study with the Big Blue mouse model has reported a mutagenic effect associated with the H. pylori infection, as a result in part of oxidative DNA damage. The present work investigates the consequences of a deficiency in the OGG1 DNA glycosylase, responsible for the excision of 8-oxo guanine, on the inflammatory and genotoxic host response to the infection. MATERIALS AND METHODS: Big Blue Ogg1-/- C57BL/6 mice were orally inoculated with H. pylori strain SS1 or vehicle only, and sacrificed after 1, 3, or 6 months. The serologic response, histologic lesions, mutant frequency, and spectra of mutations were assessed in the stomach and compared to what observed in the wild-type (Wt) context. RESULTS: Inflammatory lesions induced in the gastric mucosa of H. pylori-infected mice, corresponding to a moderate gastritis, were less severe in Ogg1-/- than in Wt Big Blue mice. Analysis of antimicrobial humoral immunity exhibited a lower IgG2a serum level (Th1 response) after 6 months of infection in Ogg1-/- than in the Wt mice. In these conditions, the H. pylori-SS1infection in the Ogg1-/- mice did not induce a mutagenic effect at the gastric epithelial cells level, either after 3 or 6 months. CONCLUSIONS: The inactivation of the OGG1 DNA glycosylase in mouse leads to less severe inflammatory lesions and abolished the mutagenic effect at the gastric epithelial cells level, induced by the H. pylori infection. These data suggest for the OGG1deficiency a protective role against inflammation and genotoxicity associated to the H. pylori infection.
Authors: Torkild Visnes; Armando Cázares-Körner; Wenjing Hao; Olov Wallner; Geoffrey Masuyer; Olga Loseva; Oliver Mortusewicz; Elisée Wiita; Antonio Sarno; Aleksandr Manoilov; Juan Astorga-Wells; Ann-Sofie Jemth; Lang Pan; Kumar Sanjiv; Stella Karsten; Camilla Gokturk; Maurice Grube; Evert J Homan; Bishoy M F Hanna; Cynthia B J Paulin; Therese Pham; Azita Rasti; Ulrika Warpman Berglund; Catharina von Nicolai; Carlos Benitez-Buelga; Tobias Koolmeister; Dag Ivanic; Petar Iliev; Martin Scobie; Hans E Krokan; Pawel Baranczewski; Per Artursson; Mikael Altun; Annika Jenmalm Jensen; Christina Kalderén; Xueqing Ba; Roman A Zubarev; Pål Stenmark; Istvan Boldogh; Thomas Helleday Journal: Science Date: 2018-11-16 Impact factor: 47.728
Authors: Barbara Tudek; Alicja Winczura; Justyna Janik; Agnieszka Siomek; Marek Foksinski; Ryszard Oliński Journal: Am J Transl Res Date: 2010-05-15 Impact factor: 4.060