ENDOGENOUS HYPERGASTRINEMIA DOES NOT PROMOTE GROWTH OF COLONIC MUCOSAOR OF A TRANSPLANTED COLON ADENOCARCINOMA IN RATS

Background/Objective Gastrin is trophic for the mucosa of the acid-pro ducing part of the rat stomach, notably the histamine-producing ECL ce lls. Gastrin is said to stimulate growth also of colonic mucosa and co lon cancer. The purpose of the present study was to examine whether en dogenous hypergastrinaemia had trophic effects on normal colonic mucos a and transplanted colon adenocarcinoma in rats. Methods Rats were sub jected to fundectomy (surgical removal of the acid-producing part of t he stomach) or treatments known to induce endogenous hypergastrinaemia . The treatments included refeeding after 48 h of food deprivation or administration of omeprazole (400 mu mol/kg/day, orally). Other operat ions included colostomy and sham operation. A K12-cell line, originall y established from a 1,2-dimethylhydrazine-induced colon adenocarcinom a, was used for transplantation. The rates of cell proliferation were determined in the oxyntic and colonic mucosa and in the tumour by meas uring the proportion of the cells that accumulated bromodeoxyuridine i n their nuclei, i,e, the labelling index (LI), The thickness of the ox yntic mucosa and the activity of histidine decarboxylase (HDC), the hi stamine-forming enzyme of the ECL cells, were measured. In addition, t he thickness of the colonic mucosa and the weight and volume of the tu mour were measured. Results Refeeding or treatment with a single dose of omeprazole in fasted rats raised the serum gastrin concentration an d the LI and HDC activity in the oxyntic mucosa; refeeding but not ome prazole raised the LI in the colonic mucosa. In fed rats, hypergastrin aemia 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, Conclusion Endogenous hypergastrinaemia did not induce trophic effects on rat colonic mucosa and did not promote growth of a transplanted co lon adenocarcinoma in the rat (C) 1998 Lippincott-Raven Publishers.