Effects of alpha-difluoromethylornithine on pancreatic growth induced by caerulein.

The role of ornithine decarboxylase and of polyamines was investigated on caerulein-induced pancreatic growth by the use of alpha-difluoromethylornithine (DFMO), an enzyme-activated irreversible inhibitor of ornithine decarboxylase. By itself, DFMO did not affect the pancreatic gland at all but when combined with caerulein, it reduced the increases in DNA synthesis and DNA content initiated by the cholecystokinin analog. The general hypertrophic action of caerulein was not affected by DFMO but specific increases in amylase and chymotrypsin concentrations were observed after 2 days of caerulein. The effect on amylase concentration was further increased after 4 days but that on chymotrypsin was reversed, showing a significant decrease. These data suggest that the polyamines might be involved in pancreatic growth that is stimulated by caerulein and that their action could be mainly oriented towards cellularity. The specific decreases obtained in DNA synthesis and content brought about by DFMO support this observation.