Helicobacter pylori causes DNA damage in gastric epithelial cells.
Helicobacter pylori infection has been considered as a risk factor for gastric carcinoma. Strong evidence exists that reactive oxygen species (ROS) play an important role in carcinogenesis, and in vivo investigations have shown increased synthesis of ROS in the gastric mucosa of H.pylori-infected patients. In the present study the direct effects of H.pylori on ROS and DNA synthesis, induction of apoptosis and DNA repair were investigated in the gastric epithelial cell lines AGS and HM02. Incubation of gastric cells with H.pylori extract induced the synthesis of ROS, diminished the levels of reduced glutathione (GSH), induced DNA fragmentation and increased DNA synthesis in gastric cells. Poly(ADP-ribose) formation was increased in gastric cells exposed to H.pylori extract. FACS analysis of gastric cells exposed to H.pylori extract did not reveal any change in the percentage of cells in the G(2)/M phase of the cell cycle. The radical scavengers MnTBAP (a cell permeable superoxide dismutase mimic), ebselen (a GSH peroxidase mimic) and high doses of catalase completely blocked H.pylori extract-induced elevation in DNA synthesis. Our results indicate that H.pylori extract directly induces the synthesis of ROS in gastric epithelial cells and causes DNA damage.
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Department of General Pharmacology, Hannover Medical School, D-30625 Hannover, Germany.
Wagner
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Sewing
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Beil
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W
D002453:Cell Cycle; D004249:DNA Damage; D004261:DNA Replication; D004815:Epidermal Growth Factor / Q000494:pharmacology; D004847:Epithelial Cells / Q000378:metabolism / Q000382:microbiology; D005753:Gastric Mucosa / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D016480:Helicobacter pylori / Q000472:pathogenicity*; D006801:Humans; D011064:Poly Adenosine Diphosphate Ribose / Q000378:metabolism; D017382:Reactive Oxygen Species; D013270:Stomach / Q000166:cytology / Q000187:drug effects / Q000382:microbiology*; D013936:Thymidine / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D017382:Reactive Oxygen Species; D011064:Poly Adenosine Diphosphate Ribose; D004815:Epidermal Growth Factor; D005978:Glutathione; D013936:Thymidine