title: Dietary supplementation with carbonate increases expression of ornithine decarboxylase and proliferation in gastric mucosa in a rat model of gastric cancer.
abstract: 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.
authors.affiliation: Division of Pathology, Department of Laboratory Medicine of Lund University, Malmö University Hospital, Malmö, Sweden. roy.ehrnstrom@med.lu.se
authors.forename: Roy A
authors.initials: RA
authors.lastname: Ehrnström
authors.forename: Lars Magnus
authors.initials: LM
authors.lastname: Bjursten
authors.forename: Otto
authors.initials: O
authors.lastname: Ljungberg
authors.forename: Béla
authors.initials: B
authors.lastname: Veress
authors.forename: Monica E
authors.initials: ME
authors.lastname: Haglund
authors.forename: Clas G
authors.initials: CG
authors.lastname: Lindström
authors.forename: Tommy
authors.initials: T
authors.lastname: Andersson
mesh_terms: 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
chemical_list: D017693:Sodium Bicarbonate; D051546:Cyclooxygenase 2; C489691:Ptgs2 protein, rat; D009955:Ornithine Decarboxylase