PROMOTION OF CHOLANGIOCARCINOGENESIS IN THE HAMSTER LIVER BY BILE-DUCT LIGATION AFTER DIMETHYLNITROSAMINE INITIATION

Administration of hepatocarcinogenic nitrosamines before or after infe ction with the liver fluke, Opisthorchis viverrini (OV), results in ma rked development of cholangiocellular and hepatocellular precancerous and cancerous lesions in the hamster liver. The promoting effects of O V are believed to be exerted either mechanically, chemically or immuno logically. To test the influence of possible mechanical effects, Syria n hamsters were initiated with a single i.p. injection of dimethylnitr osamine (DMN) 20 mg/kg and subjected 2 weeks later either to a sham op eration or to complete ligation of the extrahepatic bile duct to the l eft lateral lobe. At the end of week 40, the animals receiving DMN-ini tiation and ligation had a 60.9% incidence of cholangiofibrosis, 21.7% of mucous cystadenomas and 39.1% of cholangiocarcinomas, whereas the group given DMN alone only developed cholangiofibrosis, limited to 5% of the animals. In the latter case neither cystadenomas nor cholangioc arcinomas were observed. The incidence of hepatocellular nodules did n ot differ between the two groups and no tumorous lesions developed in either the ligated or the untreated groups without DMN pretreatment. C omplete ligation of the bile duct itself led to a series of events; ob struction of bile flow being followed by dilatation, cyst formation, a nd necrosis of the bile duct epithelium and surrounding affected areas leading to regenerative proliferation. The results are in line with t he conclusion that parasite-associated proliferation in target cell po pulations is, at least in part, responsible for the influence of OV on liver tumor development.