Preneoplastic changes in rabbit pancreatic duct cells produced by dimethylhydrazine

Permeation catheters containing 40% dimethylhydrazine (DMH) were implanted into the main pancreatic duct of New Zealand white rabbits. The catheters were constructed of silicone polycarbonate with a 4- to 10-day carcinogen release rate. Rabbits implanted with catheters containing DMH showed pancreatic ductal cell hyperplasia, metaplasia and dysplasia with periductal cell infiltration, adenosis and adenoma formation. These changes began approximately 9 to 12 weeks after implantation and persisted for 75 to 80 weeks. Specificity of the delivery system appeared to be excellent in that pathologic effects were observed only in the pancreatic and peripancreatic tissues. Moreover, these effects were probably directly related to the implanted carcinogen since similar maintained effects were not observed in control animals.