Carcinogenesis and change in the biliary epithelium in a hamster CDDB model without carcinogen *
It is well known that pancreaticobiliary maljunction (PBM) in the pancreatobiliary system promotes development of biliary carcinoma in man. The reflux of pancreatic juice into the biliary tract is considered to be one factor promoting biliary carcinoma. Therefore, we carried out a cholecystoduodenostomy with dissection of the extrahepatic bile duct at the distal end of the common duct (CDDB) in hamsters in such a way that pancreatic juice and duodenal contents would enter the biliary tract. After with CDDB, all the animals were fed a basal diet and provided drinking water ad libitum without the use of a carcinogen until they were sacrificed at 6 months or 12 months. In the six-month group, hyperplasia of the epithelium in the gallbladder was observed in 100 %. Severe dysplasia of the epithelium in the gallbladder was noted in one out of six hamsters. The cell kinetics of the gallbladder epithelium were examined using the PCNA-labeling index (PCNA LI). A high PCNA LI in the epithelium of the gallbladder was demonstrated in hamsters that had undergone CDDB but not in those who had not. Although inflammatory cells permeated the epithelium of the extrahepatic bile duct, no hyperplasia was observed. No pathological findings were made in the liver or pancreas. In the 12 month group, hyperplasia of the epithelium of the gallbladder was observed in 100% and of the extrahepatic bile duct in 50%. Extrahepatic bile duct carcinoma was found in 1 out of 14 hamsters. K-ras gene mutation was not detected. In conclusion, the CDDB procedure itself greatly accelerated cell turn-over of the epithelium in the extrahepatic biliary system. We could observe extrahepatic biliary carcinogenesis in the model without a carcinogen. This model allows for observation of the process from hyperplasia to carcinoma without the use of a carcinogen, and is a useful model for investigating and clarifying the mechanism of carcinogenesis in the extrahepatic biliary system. (Accepted on October 18, 2002) Kawasaki Igakkaishi 28(4) : 279-286, 2002
