Ammonia inhibits proliferation and cell cycle progression at S-phase in human gastric cells

Helicobacter pylori (Hp) has strong urease activity and produces a large amount of ammonia in the stomach. In animal studies, ammonia was shown to accelerate cell kinetics of gastric mucosa, and long-term exposure of the stomach to ammonia leads to mucosal atrophy. To understand this process, we exa...

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Bibliographic Details
Published in:Digestive diseases and sciences 1997-07, Vol.42 (7), p.1394-1399
Main Authors: MATSUI, T, MATSUKAWA, Y, SAKAI, T, NAKAMURA, K, AOIKE, A, KAWAI, K
Format: Article
Language:English
Subjects:
Adenocarcinoma - pathology
Ammonia - pharmacology
Biological and medical sciences
Carcinoma, Adenosquamous - pathology
Cell Cycle - drug effects
Cell differentiation, maturation, development, hematopoiesis
Cell Division - drug effects
Cell physiology
DNA, Neoplasm - biosynthesis
DNA, Neoplasm - drug effects
Dose-Response Relationship, Drug
Flow Cytometry
Fundamental and applied biological sciences. Psychology
Humans
Hydrogen-Ion Concentration
Molecular and cellular biology
S Phase
Stomach Neoplasms - pathology
Tumor Cells, Cultured - drug effects
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Summary:Helicobacter pylori (Hp) has strong urease activity and produces a large amount of ammonia in the stomach. In animal studies, ammonia was shown to accelerate cell kinetics of gastric mucosa, and long-term exposure of the stomach to ammonia leads to mucosal atrophy. To understand this process, we examined the effects of ammonia on the growth and cell cycle progression of human gastric cancer cell lines (HGC-27, MKN1, MKN45) using flow-cytometric analysis. In each cell line, ammonia inhibited the cell growth in a dose-dependent manner and caused significant 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 addition of ammonium chloride at the same concentration, while adjusting the pH of the media with NaOH alone to that with the cytostatic dose of ammonia did not affect the cell cycle progression. These observations indicate that ammonia induces S-phase arrest in gastric cells independently of pH.
ISSN:0163-2116
1573-2568
DOI:10.1023/A:1018837920769