Effect of hypergastrinemia on pancreatic carcinogenesis.
BACKGROUND
Previous studies in our laboratory demonstrated that pancreatic carcinomas in rodents express receptors for the peptide hormone gastrin that are not present in normal adult pancreas. In view of an abundant literature suggesting that gastrin may promote growth of various gastrointestinal tissues and tumors, the effect of hypergastrinemia on the process of pancreatic carcinogenesis was evaluated.


METHODS
Rats received subcutaneous injections of the pancreatic carcinogen azaserine at 19 and 26 days of age. Starting at 12 months of age, animals were randomized to treatment with the proton pump inhibitor lansoprazole or vehicle by gavage for 6 months. At autopsy, pancreatic wet weight normalized to body weight was recorded, as well as the number of benign and malignant pancreatic lesions.


RESULTS
Serum gastrin levels were determined by radioimmunoassay and showed a greater than two-fold increase in lansoprazole-treated animals. Pancreatic wet weight in hypergastrinemic rats was increased compared to controls (p <0.05). Premalignant lesions such as acidophilic atypical acinar cell foci, adenomas, heterogeneous phenotypic populations of nodules within nodules, and carcinoma-in-situ were not increased in the hypergastrinemic group. Likewise, there was no difference in the incidence of invasive carcinoma in hypergastrinemic animals (10%) compared to controls (5.7%).


CONCLUSIONS
Hypergastrinemia stimulated an increase in pancreatic weight, but did not stimulate development of premalignant lesions or progression to cancer in the azaserine model of rat pancreatic acinar cell carcinoma.
McDonald
Jerome M
JM
Department of Surgery, Veterans Affairs Puget Sound Health Care System and the University of Washington School of Medicine, Seattle, WA 98108, USA.
Longnecker
Daniel S
DS
Bell
Richard H
RH
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000236:Adenoma / Q000139:chemically induced / Q000473:pathology*; D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology; D001377:Azaserine; D002278:Carcinoma in Situ / Q000139:chemically induced / Q000473:pathology; D018267:Carcinoma, Acinar Cell / Q000139:chemically induced / Q000473:pathology; D004195:Disease Models, Animal; D005755:Gastrins / Q000097:blood* / Q000187:drug effects / Q000502:physiology; D064747:Lansoprazole; D008297:Male; D009853:Omeprazole / Q000031:analogs & derivatives* / Q000494:pharmacology; D009929:Organ Size; D010179:Pancreas / Q000187:drug effects / Q000473:pathology*; D010190:Pancreatic Neoplasms / Q000139:chemically induced / Q000473:pathology*; D011230:Precancerous Conditions / Q000139:chemically induced / Q000473:pathology; D051381:Rats; D011917:Rats, Inbred Lew
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000897:Anti-Ulcer Agents; D005755:Gastrins; D064747:Lansoprazole; D001377:Azaserine; D009853:Omeprazole