Endogenous hypergastrinaemia does not promote growth of colonic mucosa or of a transplanted colon adenocarcinoma in rats. 1998

D Chen, and M Destrée, and R Håkanson, and G Willems
Department of Pharmacology, University of Lund, Sweden.

OBJECTIVE Gastrin is trophic for the mucosa of the acid-producing part of the rat stomach, notably the histamine-producing ECL cells. Gastrin is said to stimulate growth also of colonic mucosa and colon cancer. The purpose of the present study was to examine whether endogenous hypergastrinaemia had trophic effects on normal colonic mucosa and transplanted colon adenocarcinoma in rats. METHODS Rats were subjected to fundectomy (surgical removal of the acid-producing part of the stomach) or treatments known to induce endogenous hypergastrinaemia. The treatments included refeeding after 48 h of food deprivation or administration of omeprazole (400 micromol/kg/day, orally). Other operations included colostomy and sham operation. A K12-cell line, originally established from a 1,2-dimethylhydrazine-induced colon adenocarcinoma, was used for transplantation. The rates of cell proliferation were determined in the oxyntic and colonic mucosa and in the tumour by measuring the proportion of the cells that accumulated bromodeoxyuridine in their nuclei, i.e. the labelling index (LI). The thickness of the oxyntic mucosa and the activity of histidine decarboxylase (HDC), the histamine-forming enzyme of the ECL cells, were measured. In addition, the thickness of the colonic mucosa and the weight and volume of the tumour were measured. RESULTS Refeeding or treatment with a single dose of omeprazole in fasted rats raised the serum gastrin concentration and the LI and HDC activity in the oxyntic mucosa; refeeding but not omeprazole raised the LI in the colonic mucosa. In fed rats, hypergastrinaemia induced by fundectomy or treatment with omeprazole (for 10 days) failed to affect either the LI or the thickness of the mucosa of the proximal colon and the excluded distal colon of the colostomized rats. Fundectomy failed to stimulate the growth of the tumour transplants. CONCLUSIONS Endogenous hypergastrinaemia did not induce trophic effects on rat colonic mucosa and did not promote growth of a transplanted colon adenocarcinoma in the rat.

UI MeSH Term Description Entries
D007413 Intestinal Mucosa Lining of the INTESTINES, consisting of an inner EPITHELIUM, a middle LAMINA PROPRIA, and an outer MUSCULARIS MUCOSAE. In the SMALL INTESTINE, the mucosa is characterized by a series of folds and abundance of absorptive cells (ENTEROCYTES) with MICROVILLI. Intestinal Epithelium,Intestinal Glands,Epithelium, Intestinal,Gland, Intestinal,Glands, Intestinal,Intestinal Gland,Mucosa, Intestinal
D008297 Male Males
D009368 Neoplasm Transplantation Experimental transplantation of neoplasms in laboratory animals for research purposes. Transplantation, Neoplasm,Neoplasm Transplantations,Transplantations, Neoplasm
D009853 Omeprazole A 4-methoxy-3,5-dimethylpyridyl, 5-methoxybenzimidazole derivative of timoprazole that is used in the therapy of STOMACH ULCERS and ZOLLINGER-ELLISON SYNDROME. The drug inhibits an H(+)-K(+)-EXCHANGING ATPASE which is found in GASTRIC PARIETAL CELLS. H 168-68,Omeprazole Magnesium,Omeprazole Sodium,Prilosec,H 168 68,H 16868,Magnesium, Omeprazole,Sodium, Omeprazole
D010295 Parietal Cells, Gastric Rounded or pyramidal cells of the GASTRIC GLANDS. They secrete HYDROCHLORIC ACID and produce gastric intrinsic factor, a glycoprotein that binds VITAMIN B12. Gastric Parietal Cells,Oxyntic Cells,Cell, Gastric Parietal,Cell, Oxyntic,Cells, Gastric Parietal,Cells, Oxyntic,Gastric Parietal Cell,Oxyntic Cell,Parietal Cell, Gastric
D002455 Cell Division The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION. M Phase,Cell Division Phase,Cell Divisions,Division Phase, Cell,Division, Cell,Divisions, Cell,M Phases,Phase, Cell Division,Phase, M,Phases, M
D003106 Colon The segment of LARGE INTESTINE between the CECUM and the RECTUM. It includes the ASCENDING COLON; the TRANSVERSE COLON; the DESCENDING COLON; and the SIGMOID COLON. Appendix Epiploica,Taenia Coli,Omental Appendices,Omental Appendix,Appendices, Omental,Appendix, Omental
D003110 Colonic Neoplasms Tumors or cancer of the COLON. Cancer of Colon,Colon Adenocarcinoma,Colon Cancer,Cancer of the Colon,Colon Neoplasms,Colonic Cancer,Neoplasms, Colonic,Adenocarcinoma, Colon,Adenocarcinomas, Colon,Cancer, Colon,Cancer, Colonic,Cancers, Colon,Cancers, Colonic,Colon Adenocarcinomas,Colon Cancers,Colon Neoplasm,Colonic Cancers,Colonic Neoplasm,Neoplasm, Colon,Neoplasm, Colonic,Neoplasms, Colon
D004791 Enzyme Inhibitors Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction. Enzyme Inhibitor,Inhibitor, Enzyme,Inhibitors, Enzyme
D005755 Gastrins A family of gastrointestinal peptide hormones that excite the secretion of GASTRIC JUICE. They may also occur in the central nervous system where they are presumed to be neurotransmitters. Gastrin

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