Effect of antrectomy in hypergastrinaemic female Japanese cotton rats.
OBJECTIVE
Female Japanese cotton rats become hypoacidic and hypergastrinaemic from age 2 months and later develop gastric carcinomas in the oxyntic mucosa. Previous studies have demonstrated that carcinogenesis can be halted by a gastrin receptor antagonist and that carcinomas can be induced by a histamine-2 receptor antagonist or partial corpectomy, both of which induce hypergastrinaemia. The aim of the present study was to examine the effect of antrectomy in female cotton rats.


METHODS
The animals were either antrectomized (Group 1) or sham-operated (Group 2) 2 months after detection of hypergastrinaemia and terminated 4 months after operation. A third group was antrectomized at age 2 months while still normo-acidic (Group 3) and terminated 6 months after operation.


RESULTS
Antrectomy after 2 months of hypergastrinaemia prevented the development of carcinoma compared with in sham-operated animals, whereas some of the animals that were antrectomized at 2 months of age also developed carcinomas. In Groups 1 and 2 as well as in animals developing carcinomas in Group 3, there was marked hyperplasia of neuroendocrine cells in the oxyntic mucosa expressing chromogranin A, vesicular monoamine transporter (VMAT)-2, ghrelin and somatostatin. Gastrin-positive cells were found adjacent to neoplastic areas in the oxyntic mucosa.


CONCLUSIONS
The removal of antral gastrin by antrectomy halts carcinogenesis in cotton rats, but other mechanisms may also play a role.
Bakkelund
Karin
K
Department of Cancer Research and Molecular Medicine, Faculty of Medicine, NTNU, Trondheim, Norway. karin.bakkelund@ntnu.no
Fossmark
Reidar
R
Nordrum
Ivar S
IS
Waldum
Helge L
HL
D000818:Animals; D002277:Carcinoma / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D004195:Disease Models, Animal; D005260:Female; D005743:Gastrectomy / Q000379:methods; D005755:Gastrins / Q000378:metabolism*; D006728:Hormones / Q000378:metabolism*; D011706:Pyloric Antrum / Q000378:metabolism / Q000473:pathology / Q000601:surgery*; D016205:Sigmodontinae; D013274:Stomach Neoplasms / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*
D005755:Gastrins; D006728:Hormones