Endogenous hypergastrinaemia does not promote growth of colonic mucosa or of a transplanted colon adenocarcinoma in rats.
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.
Chen
D
D
Department of Pharmacology, University of Lund, Sweden.
Destrée
M
M
Håkanson
R
R
Willems
G
G
D000230:Adenocarcinoma / Q000473:pathology; D000818:Animals; D002455:Cell Division; D003106:Colon / Q000473:pathology*; D003110:Colonic Neoplasms / Q000473:pathology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005755:Gastrins / Q000097:blood* / Q000502:physiology; D007413:Intestinal Mucosa / Q000473:pathology* / Q000502:physiology; D008297:Male; D009368:Neoplasm Transplantation; D009853:Omeprazole / Q000494:pharmacology; D010295:Parietal Cells, Gastric / Q000473:pathology* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley
D004791:Enzyme Inhibitors; D005755:Gastrins; D009853:Omeprazole