Role of cholecystokinin in dietary fat-promoted azaserine-induced pancreatic carcinogenesis in rats.
The role of cholecystokinin in dietary fat-promoted pancreatic carcinogenesis was investigated in azaserine-treated rats, using lorglumide, a highly specific cholecystokinin-receptor antagonist. The animals were killed 8 months after the start of treatment. Cholecystokinin, but not dietary unsaturated fat, increased pancreatic weight. Rats treated with cholecystokinin developed more acidophilic atypical acinar cell nodules, adenomas and adenocarcinomas than control animals. Rats maintained on the high-fat diet developed significantly more adenomas and adenocarcinomas than controls given a diet low in unsaturated fat. Lorglumide largely inhibited the enhancing effect of cholecystokinin, but not of dietary fat, on pancreatic carcinogenesis indicating that it is unlikely that the promoting effect of dietary unsaturated fat on pancreatic carcinogenesis is mediated via cholecystokinin.
Appel
M J
MJ
Department of Biological Toxicology, TNO Toxicology and Nutrition Institute, Zeist, The Netherlands.
Meijers
M
M
Van Garderen-Hoetmer
A
A
Lamers
C B
CB
Rovati
L C
LC
Sprij-Mooij
D
D
Jansen
J B
JB
Woutersen
R A
RA
D000818:Animals; D001377:Azaserine / Q000494:pharmacology*; D001835:Body Weight; D002766:Cholecystokinin / Q000502:physiology*; D004041:Dietary Fats; D008099:Liver / Q000033:anatomy & histology / Q000187:drug effects / Q000473:pathology; D008297:Male; D009929:Organ Size; D010179:Pancreas / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000209:etiology* / Q000473:pathology; D011377:Proglumide / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011949:Receptors, Cholecystokinin / Q000037:antagonists & inhibitors* / Q000502:physiology
D004041:Dietary Fats; D011949:Receptors, Cholecystokinin; D001377:Azaserine; D002766:Cholecystokinin; D011377:Proglumide; C048181:lorglumide