Studies of the effect of cerulein administration on experimental pancreatic carcinogenesis

The influence of the cholecystokinin analogue cerulein on induced pancreatic cancer in the Syrian golden hamster was investigated. Of hamsters given weekly subcutaneous injection of N-nitrosobis(2-hydroxypropyl)amine (BHP) in initial experiments 50% succumbed within 30 weeks when a dose of 125 mg BHP per kg body weight was used and within 25 weeks after the double dose. An induction time of at most 24 weeks was therefore used in the subsequent experiments. Administration of cerulein (2 micrograms twice daily for 5 days a week) for 18 or 22 weeks caused an increase of pancreatic wet weight by about 100% and of pancreatic protein content by 73% (18 weeks). BHP did not influence the pancreatic weight either in hamsters given cerulein or in those given saline injections. BHP (125 mg/kg) caused tumors in 44% of the animals after 18 weeks and in 73% after 22 weeks. When BHP was given in a dose of 250 mg/kg, 100% of the animals had pancreatic tumors after 22 weeks. At neither dose and neither time interval did cerulein influence the number of tumor-bearing animals, number of cancer-bearing animals, or number of tumors per tumor-bearing animal or cancers per cancer-bearing animal. No morphological differences were found within the lesions of animals given only BHP as compared with those given cerulein in addition. All lesions were of ductal appearance. The distribution of tumors was also similar irrespective of the treatment given. The results show that cerulein does not influence experimental pancreatic carcinogenesis in the Syrian golden hamster, possibly reflecting that cerulein and BHP primarily act on different target cells.