ANALYSIS OF CELL-DAMAGE AND PROLIFERATION IN HELICOBACTER PYLORI-INFECTED HUMAN GASTRIC-MUCOSA FROM PATIENTS WITH GASTRIC ADENOCARCINOMA

Helicobacter pylori (HP) infection, a cause of multifocal atrophic gas tritis, is considered an important factor related to the evolution of the human gastric mucosa from normal to intestinal-type adenocarcinoma . We examined cell proliferation and both double and single strand DNA damage is situ in 35 patients undergoing gastrectomy for adenocarcino ma with HP-infected gastric mucosa by immunolocalization of Ki-67, ter minal deoxynucleotidyl transferase-mediated dUTP-biotin nick end label ing, and in situ nick translation. We also studied the distribution of intraepithelial neutrophils by elastase immunolocalization. HP infect ion was confirmed in all cases by serum anti-HP antibodies, urease tes ting, and histopathological examination, HP-infected gastric mucosa wa s classified according to the degree of inflammation and intestinal me taplasia, Ki-67, terminal deoxynucleotidyl transferase-mediated labeli ng, in situ nick translation, and intraepithelial neutrophil indices a ll increased with the progression of gastritis and were highest in gla nds with incomplete intestinal metaplasia, All indices were lowest in gastric glands with complete intestinal metaplasia, Significant positi ve correlations were observed among these markers, Increased prolifera tive activity in HP-associated chronic gastritis in response to cell d amage of injury was clearly demonstrated, suggesting that both HP-asso ciated toxins and intraepithelial neutrophils are important in HP-rela ted gastric epithelial injury, Increased cell turnover associated with incomplete intestinal metaplasia may result in DNA Instability and su bsequent development of intestinal-type gastric adenocarcinoma in HP-i nfected mucosa.