Dietary supplementation with carbonate increases expression of ornithine decarboxylase and proliferation in gastric mucosa in a rat model of gastric cancer.
Dietary factors play essential roles in gastric carcinogenesis. We recently found that dietary supplementation with NaHCO(3) 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 NaHCO(3). 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.
Ehrnström
Roy A
RA
Division of Pathology, Department of Laboratory Medicine of Lund University, Malmö University Hospital, Malmö, Sweden. roy.ehrnstrom@med.lu.se
Bjursten
Lars Magnus
LM
Ljungberg
Otto
O
Veress
Béla
B
Haglund
Monica E
ME
Lindström
Clas G
CG
Andersson
Tommy
T
D000230:Adenocarcinoma / Q000139:chemically induced / Q000473:pathology; D000818:Animals; D049109:Cell Proliferation; D051546:Cyclooxygenase 2 / Q000378:metabolism; D019587:Dietary Supplements / Q000009:adverse effects*; D004195:Disease Models, Animal; D005753:Gastric Mucosa / Q000201:enzymology* / Q000473:pathology; D018530:Gastric Stump; D007124:Immunoenzyme Techniques; D008297:Male; D009955:Ornithine Decarboxylase / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D017693:Sodium Bicarbonate / Q000009:adverse effects*; D013274:Stomach Neoplasms / Q000139:chemically induced / Q000201:enzymology* / Q000473:pathology
D017693:Sodium Bicarbonate; D051546:Cyclooxygenase 2; C489691:Ptgs2 protein, rat; D009955:Ornithine Decarboxylase