EFFECT OF CHOLECYSTOKININ ANALOG CERULEIN AND CHOLECYSTOKININ ANTAGONIST LORGLUMIDE ON PANCREATIC CARCINOGENESIS IN THE RAT

The effects of the cholecystokinin (CCK)-analogue, caerulein, and CCK- receptor antagonist lorglumide (CR-1409) on pancreatic carcinogenesis induced by 7,12-dimethylbenz(a)anthracene (DMBA) were studied. One hun dred thirty rats were divided into the following 10 treatment groups: group 1, DMBA (2-3 mg); group 2, DMBA + caerulein (5 mug/kg); group 3, DMBA + caerulein + CR-1409 (12 mg/kg); group 4, caerulein + DMBA; gro up 5, caerulein + CR-1409 + DMBA; group 6, DMBA + CR-1409; group 7, CR -1409 + DMBA; group 8, caerulein; group 9, CR-1409; and group 10, sham operation + saline. DMBA was surgically implanted into the pancreas. Caerulein and/or CR- 1409 was administered twice daily for 15 days aft er (in groups 2, 3, and 6) or before (in groups 4, 5, and 7) DMBA impl antation. Six months after carcinogen administration, all rats were sa crificed and autopsied. The incidence of pancreatic cancer appeared si gnificantly (P < 0.001) increased when caerulein was administered foll owing DMBA implantation. CR-1409 significantly inhibited (P < 0.02) ca erulein effects and reduced tumor growth when injected after carcinoge n exposure. (C) 1994 Wiley-Liss, Inc.