AMMONIA INHIBITS PROLIFERATION AND CELL-CYCLE PROGRESSION AT S-PHASE IN HUMAN GASTRIC CELLS

Helicobacter pylori (Wp) has strong urease activity and produces a lar ge amount of ammonia in the stomach. In animal studies, ammonia was sh own to accelerate cell kinetics of gastric mucosa, and long-term expos ure of the stomach to ammonia leads to mucosal atrophy. To understand this process, we examined the effects of ammonia on the growth and cel l cycle progression of human gastric cancer cell lines (HGC-27, MKN1, MKN45) using flow-cytometric analysis. In each cell line, ammonia inhi bited the cell growth in a dose-dependent manner and caused significan t accumulation of S-phase cells at a cytostatic dose. DNA synthesis of HGC-27 cells treated with ammonia was also suppressed to about 50% of that of the untreated cells. Similar effects were observed on additio n of ammonium chloride at the same concentration? while adjusting the pH of the media with NaOH alone to that with the cytostatic dose of am monia did not affect the cell cycle progression. These observations in dicate that ammonia induces S-phase arrest in gastric cells independen tly of pH.