Ammonia Inhibits Proliferation and Cell Cycle Progression at S-Phase in Human Gastric Cells

Helicobacter pylori (Hp) has strong ureaseactivity and produces a large amount of ammonia in thestomach. In animal studies, ammonia was shown toaccelerate cell kinetics of gastric mucosa, andlong-term exposure of the stomach to ammonia leads tomucosal atrophy. To understand this process, we examinedthe effects of ammonia on the growth and cell cycleprogression of human gastric cancer cell lines (HGC-27, MKN1, MKN45) using flowcytometric analysis. Ineach cell line, ammonia inhibited the cell growth in adose-dependent manner and caused significantaccumulation of S-phase cells at a cytostatic dose. DNA synthesis of HGC-27 cells treated with ammoniawas also suppressed to about 50% of that of theuntreated cells. Similar effects were observed onaddition of ammonium chloride at the same concentration, while adjusting the pH of the media with NaOHalone to that with the cytostatic dose of ammonia didnot affect the cell cycle progression. Theseobservations indicate that ammonia induces S-phasearrest in gastric cells independently of pH.