Gastrin-mediated alterations in gastric epithelial apoptosis and proliferation in a mastomys rodent model of gastric neoplasia.
OBJECTIVE
Hypergastrinemia secondary to low acid secretion is associated with gastric carcinoid formation in Mastomys. We investigated the effect of gastrin on oxyntic epithelial apoptosis and proliferation in this model.


METHODS
Hypergastrinemia and mucosal hyperplasia were induced by irreversible H(2) receptor blockade with loxtidine. Gastrin levels were normalised in some animals by 10 days' loxtidine withdrawal. Serum gastrin was determined by radioimmunoassay, proliferative, enterochromaffin-like cells and Bcl-2 protein family expression by immunohistochemistry, and apoptotic cells by terminal deoxyuridine nucleotide nick end labeling (TUNEL).


RESULTS
Proliferating cells were increased 4-fold in loxtidine-treated animals, and returned to normal upon loxtidine withdrawal. Enterochromaffin-like cell number increased 2-fold with loxtidine, and did not decrease after withdrawal. Apoptotic epithelial cells were located at the luminal surface and increased 1.8-fold with loxtidine, returning to control levels upon withdrawal. The ratio of proliferative to apoptotic cells was lower in the control and withdrawn groups than in the loxtidine group (0.26+/-0.05 and 0.26+/-0.08 vs. 0.77+/-0.12). With hypergastrinemia, the expression of Bcl-2 and Bak was increased and Bax decreased in the middle of the gland.


CONCLUSIONS
Hypergastrinemia is associated with alterations in both proliferation and apoptosis in Mastomys gastric mucosa. This may contribute to the pathogenesis of mucosal hyperplasia in this model.
Kidd
M
M
Gastrointestinal Clinic, UCT Medical School Observatory, Cape Town, South Africa.
Tang
L H
LH
Modlin
I M
IM
Zhang
T
T
Chin
K
K
Holt
P R
PR
Moss
S F
SF
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002276:Carcinoid Tumor / Q000209:etiology* / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D004195:Disease Models, Animal; D005260:Female; D005744:Gastric Acid / Q000378:metabolism; D005753:Gastric Mucosa / Q000502:physiology*; D005755:Gastrins / Q000032:analysis* / Q000493:pharmacokinetics / Q000494:pharmacology; D007150:Immunohistochemistry; D008297:Male; D009115:Muridae; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics; D013274:Stomach Neoplasms / Q000209:etiology* / Q000473:pathology
D005755:Gastrins; D019253:Proto-Oncogene Proteins c-bcl-2