Dietary supplementation with carbonate increases expression of ornithine decarboxylase and proliferation in gastric mucosa in a rat model of gastric cancer

• Published in: International journal of cancer Vol. 122; no. 4; pp. 727 - 733
• Main Authors: Ehrnström, Roy A., Bjursten, Lars Magnus, Ljungberg, Otto, Veress, Béla, Haglund, Monica E., Lindström, Clas G., Andersson, Tommy
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 15-02-2008; Wiley-Liss
• Subjects: Adenocarcinoma - chemically induced; Adenocarcinoma - pathology; Animal tumors. Experimental tumors; Animals; Biological and medical sciences; Cancer and Oncology; Cancer och onkologi; carbonateions; Cell Proliferation; Clinical Medicine; Cyclooxygenase 2 - metabolism; Dietary Supplements - adverse effects; Disease Models, Animal; Experimental digestive system and abdominal tumors; experimental gastric cancer; Gastric Mucosa - enzymology; Gastric Mucosa - pathology; Gastric Stump; Immunoenzyme Techniques; inflammation; Klinisk medicin; Male; Medical and Health Sciences; Medical sciences; Medicin och hälsovetenskap; ornithine decarboxylase; Ornithine Decarboxylase - metabolism; proliferation; Rats; Rats, Wistar; Sodium Bicarbonate - adverse effects; Stomach Neoplasms - chemically induced; Stomach Neoplasms - enzymology; Stomach Neoplasms - pathology; Tumors; Cell proliferation; Rat; Mucosa; Lyases; Stomach cancer; Epidemiology; Cancerology; experimental gastric cancer; Carboxy-lyases; Carbonates; Supplementation; Public health; Gastric disease; carbonate ions; Nutrition; proliferation; Enzyme; Rodentia; Inflammation; Ornithine decarboxylase; Malignant tumor; omithine decarboxylase; Feeding; Carbon-carbon lyases; Vertebrata; Mammalia; Diet; Animal; Risk factor; Digestive diseases; Cancer
• ISSN: 0020-7136; 1097-0215
• DOI: 10.1002/ijc.23151

Dietary factors play essential roles in gastric carcinogenesis. We recently found that dietary supplementation with NaHCO3 significantly increased the development of gastric cancer in a rat gastric stump model. Here, we analysed nontransformed gastric mucosa for expression of the cancer‐related proteins cyclooxygenase‐2 (COX‐2) and ornithine decarboxylase (ODC), and we examined the relationship between expression levels of those proteins and mucosal proliferation. Research has shown that COX‐2 is upregulated in gastric mucosal inflammation and is strongly associated with gastrointestinal cancer. ODC is the key enzyme in polyamine synthesis and a regulator of cell proliferation. We performed gastric resections on 48 Wistar rats to induce spontaneous gastric cancer; half of these animals were given a normal diet, and the other half received a diet supplemented with NaHCO3. Twenty‐four unoperated rats served as a control group. The surgical procedure per se led to a significant rise in mucosal expression of COX‐2 and an associated increase in cell proliferation. However, the COX‐2 level in gastric mucosa was not further affected by dietary supplementation of carbonate. Interestingly, nontransformed gastric mucosa in the operated rats receiving a carbonate‐supplemented diet showed a pronounced increase in ODC expression that was strongly correlated with a further enhanced cell proliferation. These results indicate that carbonate ions, which represent a major constituent of intestinal reflux into the stomach, increase the expression of ODC and thereby enhance cell proliferation in nontransformed mucosa, and consequently elevate the risk of gastric cancer. © 2007 Wiley‐Liss, Inc.