Carcinogen delivery into the pancreatic duct of rabbits by means of hollow fiber capsules.

A technique is described for the delivery of various chemical agents chronically and in small doses directly into the duct of the rabbit pancreas. The feasibility of this technique is based on initial observations that implantation of a catheter delivery system in the pancreatic duct produces minimal interference with normal exocrine or endocrine pancreatic function while chronically delivering an encapsulated agent directly to the target tissues. A catheter permeation system has been designed which can be anchored in the main pancreatic duct of the New Zealand white rabbit without ligating the duct, and which will then continuously expose the ductal cells to chemical carcinogens over a 5- to 30-day period. Catheters have been successfully implanted in 177 rabbits. Examination of 37 control animals up to 182 weeks after implantation showed that, in the absence of ductal obstruction, neither the implantation procedure nor the presence of the catheter itself produced any permanent change in the morphologic structure of the pancreas. Benzo(a)pyrene produced hyperplasia, metaplasia, and adenosis, whereas methylnitrosourethane produced toxic pancreatitis and atrophy. The technique appears to be useful for evaluating the effect of carcinogens or other chemical agents when it is desirable to deliver a compound chronically and in small doses directly into the pancreatic juice.