Chronic endogenous hypercholecystokininemia promotes pancreatic carcinogenesis in the hamster.
In order to examine the effect of cholecystokinin on spontaneous and induced pancreatic carcinogenesis in the hamster, two sets of experiments were carried out, one involving long-term hypercholecystokininemia and one involving cancer induction during hypercholecystokininemia. The effect of hypercholecystokininemia, induced by pancreaticobiliary diversion (PBD), was studied for 8 months. Neither PBD animals nor sham-operated controls developed premalignant or malignant pancreatic lesions. However, in the PBD group the mean pancreatic weight, total protein content and DNA content were increased by 30, 29 and 27% respectively. No such increases were found in PBD animals receiving a cholecystokinin-A receptor antagonist during the last 24 days of the experiment. In the cancer induction study, the effect of PBD on N-nitrosobis(2-oxopropyl)amine-induced pancreatic carcinogenesis was studied for 3 months. Putative premalignant pancreatic lesions were diagnosed in all PBD hamsters and in four of 15 sham-operated controls. Pancreatic ductular carcinoma in situ was only found in PBD animals. The [3H]thymidine labeling index of the pancreatic lesions was significantly higher in the PBD group than in the controls. No such increase was observed in PBD animals receiving a cholecystokinin-A receptor antagonist during the last 5 days of the experiment. It is concluded that chronic endogenous hypercholecystokininemia promotes early phase pancreatic carcinogenesis, but does not per se cause development of premalignant or malignant pancreatic lesions in the hamster.
Chu
M
M
Department of Surgery, University Hospital of Linköping, Sweden.
Rehfeld
J F
JF
Borch
K
K
D000818:Animals; D002273:Carcinogens; D002766:Cholecystokinin / Q000097:blood*; D006224:Cricetinae; D004386:Duodenum / Q000601:surgery*; D005755:Gastrins / Q000097:blood; D008297:Male; D008647:Mesocricetus; D009602:Nitrosamines; D009929:Organ Size; D010179:Pancreas / Q000187:drug effects / Q000473:pathology; D010183:Pancreatic Ducts / Q000601:surgery*; D010190:Pancreatic Neoplasms / Q000139:chemically induced / Q000209:etiology*
D002273:Carcinogens; D005755:Gastrins; D009602:Nitrosamines; C013622:nitrosobis(2-oxopropyl)amine; D002766:Cholecystokinin