Effect of pancreatic juice reflux into biliary tract on N-nitrosobis(2-oxopropyl)amine (BOP)-induced biliary carcinogenesis in Syrian hamsters

To elucidate the possible role of pancreatic juice reflux into the biliary tract in promoting the development of biliary carcinoma, Syrian hamsters we re subjected to cholecystoduodenostomy and ligation of the distal end of th e common duct and then subcutaneously injected with N-nitrosobis(2-oxopropy l)amine (BOP) (experimental group). The incidences of gallbladder carcinoma and extrahepatic bile duct carcinoma in the experimental group was signifi cantly higher than in the sham-operated group (P < 0.01, P < 0.05). The pro liferating cell nuclear antigen (PCNA) labeling indices of both regions gra dually increased with time, and were significantly higher in the experiment al group at weeks 9 and 16 than in the sham-operated group at the same time . Trypsin and phospholipase A(2) (PLA(2)) activities in bile and tissue lev els of superoxide dismutase (SOD) in the gallbladder and extrahepatic bile ducts were higher in the experimental group than in the sham-operated group . These findings suggest that the carcinogenic effect of BOP was enhanced i n biliary epithelium that had proliferated in response to and/or had been i njured by activated pancreatic enzymes refluxing into the biliary tract and then increased free radical activity, leading to a high frequency of carci noma development in the biliary tract.