SHORT COMMUNICATION: Promotion of cholangiocarcinogenesis in the hamster liver by bile duct ligation after dimethylnitrosamine initiation

Administration of hepatocardnogenic nitrosamines before or afterinfection with the liver fluke, Opisthorchis viverrini (OV),results in marked development of cholangiocellular and hepatocellularprecancerous and cancerous lesions in the hamster liver. Thepromoting effects of OV are believed to be exerted either mechanically,chemically or immuno-logically. To test the influence of possiblemechanical effects, Syrian hamsters were initiated with a singlei.p. injection of dimethylnitrosamine (DMN) 20 mg/kg and subjected2 weeks later either to a sham operation or to complete ligationof the extrahepatic bile duct to the left lateral lobe. At theend of week 40, the animals receiving DMN-initiation and ligationhad a 60.9% incidence of cholangiofibrosis, 21.7% of mucouscystadenomas and 39.1% of cholangiocarcinomas, whereas the groupgiven DMN alone only developed cholangiofibrosis, limited to5% of the animals. In the latter case neither cystadenomas norcholangiocarcinomas were observed. The incidence of hepatocellularnodules did not differ between the two groups and no tumorouslesions developed in either the ligated or the untreated groupswithout DMN pretreatment. Complete ligation of the bile ductitself led to a series of events; obstruction of bile flow beingfollowed by dilatation, cyst formation, and necrosis of thebile duct epithelium and surrounding affected areas leadingto regenerative proliferation. The results are in line withthe conclusion that parasite-associated proliferation in targetcell populations is, at least in part, responsible for the influenceof OV on liver tumor development.