EFFECTS OF HIGH-FAT DIET AND CHOLECYSTOKININ RECEPTOR BLOCKADE ON PANCREATIC GROWTH AND TUMOR INITIATION IN THE HAMSTER

The mechanism by which high-fat diet potentiates pancreatic cancer is not known, but trophic hormones may be involved. In preliminary growth studies, hamsters fed a high fat diet (17.5% lard, 17.5% corn oil) fo r 14 days showed a 16.3% increase (P < 0.01) in pancreatic weight comp ared to controls on low fat diet (2.5% lard, 2.5% corn oil). A signifi cant increase was also seen at 28 days. Similar increases were seen in pancreatic DNA (29%, P < 0.01) and pancreatic RNA (22%, P < 0.05) at 14 days. Plasma cholecystokinin (CCK) levels at 14 days were 2.5 fold higher in the animals fed high fat (P < 0.01). Infusion of the CCK ant agonist MK329 (25 nmol/kg/h) completely abolished the increase in panc reatic weight, pancreatic DNA and pancreatic RNA. The effect of CCK re ceptor blockade during the initiation period of carcinogenesis was inv estigated in hamsters fed the same diets used in the growth studies. O ne hundred animals received a single injection of N-nitrosobis(2-oxopr opyl)amine, (BOP, 20 mg/kg). Half of the hamsters in each diet group r eceived a 2 week infusion of MK329 (25 nmol/kg/h), beginning 8 days be fore carcinogen administration. At the time of death, 55 weeks after c arcinogen administration, non-fasting plasma CCK levels were 31% highe r in the high fat fed hamsters than in the low fat fed animals (P < 0. 01). The high-fat diet group had a 3-fold increase in total cancer inc idence and a 5-fold increase in advanced lesions (adenocarcinomas). Tu mor incidence and yield were not changed in either diet group by CCK-r eceptor blockade during the initiation period. Cholecystokinin appears to mediate the short-term trophic effect that high-fat feeding has on the pancreas. However, potentiation of pancreatic cancer by high-fat diet in the hamster cancer model does not appear to be influenced by e ndogenous cholecystokinin at the time of tumor induction.