, Volume 44, Issue 1, pp 79-86

Effect of Pancreatic Juice Reflux into Biliary Tract on N-Nitrosobis(2-oxopropyl)amine (BOP)-Induced Biliary Carcinogenesis in Syrian Hamsters

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To elucidate the possible role of pancreaticjuice reflux into the biliary tract in promoting thedevelopment of biliary carcinoma, Syrian hamsters weresubjected to cholecystoduodenostomy and ligation of the distal end of the common duct and thensubcutaneously injected withN-nitrosobis(2-oxopropyl)amine (BOP) (experimentalgroup). The incidences of gallbladder carcinoma andextrahepatic bile duct carcinoma in the experimental group wassignificantly higher than in the sham-operated group (P< 0.01, P < 0.05). The proliferating cell nuclearantigen (PCNA) labeling indices of both regionsgradually increased with time, and were significantlyhigher in the experimental group at weeks 9 and 16 thanin the sham-operated group at the same time. Trypsin andphospholipase A2 (PLA2) activitiesin bile and tissue levels of superoxide dismutase (SOD) inthe gallbladder and extrahepatic bile ducts were higherin the experimental group than in the sham-operatedgroup. These findings suggest that the carcinogenic effect of BOP was enhanced in biliaryepithelium that had proliferated in response to and/orhad been injured by activated pancreatic enzymesrefluxing into the biliary tract and then increased freeradical activity, leading to a high frequency ofcarcinoma development in the biliary tract.