PMID- 11025361 OWN - NLM STAT- MEDLINE DCOM- 20010111 LR - 20181130 IS - 0012-2823 (Print) IS - 0012-2823 (Linking) VI - 62 IP - 2-3 DP - 2000 TI - Gastrin-mediated alterations in gastric epithelial apoptosis and proliferation in a mastomys rodent model of gastric neoplasia. PG - 143-51 AB - BACKGROUND/AIMS: 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 The ratio of proliferative to apoptotic cells was lower in the control and withdrawn groups than in the loxtidine group (0.26+/-0.05 and 0.26+/-0.08 vs. 0.77+/-0.12).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. CONCLUSION: 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. CI - Copyright 2000 S. Karger AG, Basel. FAU - Kidd, M AU - Kidd M AD - Gastrointestinal Clinic, UCT Medical School Observatory, Cape Town, South Africa. FAU - Tang, L H AU - Tang LH FAU - Modlin, I M AU - Modlin IM FAU - Zhang, T AU - Zhang T FAU - Chin, K AU - Chin K FAU - Holt, P R AU - Holt PR FAU - Moss, S F AU - Moss SF LA - eng GR - R29/DK48820/DK/NIDDK NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, Non-P.H.S. PT - Research Support, U.S. Gov't, P.H.S. PL - Switzerland TA - Digestion JT - Digestion JID - 0150472 RN - 0 (Gastrins) RN - 0 (Proto-Oncogene Proteins c-bcl-2) SB - IM MH - Animals MH - Apoptosis/*drug effects MH - Carcinoid Tumor/*etiology/pathology MH - Cell Division/drug effects MH - Disease Models, Animal MH - Female MH - Gastric Acid/metabolism MH - Gastric Mucosa/*physiology MH - Gastrins/*analysis/pharmacokinetics/pharmacology MH - Immunohistochemistry MH - Male MH - Muridae MH - Proto-Oncogene Proteins c-bcl-2/genetics MH - Stomach Neoplasms/*etiology/pathology EDAT- 2000/10/12 11:00 MHDA- 2001/02/28 10:01 CRDT- 2000/10/12 11:00 PHST- 2000/10/12 11:00 [pubmed] PHST- 2001/02/28 10:01 [medline] PHST- 2000/10/12 11:00 [entrez] AID - 7806 [pii] AID - 10.1159/000007806 [doi] PST - ppublish SO - Digestion. 2000;62(2-3):143-51. doi: 10.1159/000007806.