Generation of high yields of Syrian hamster cholangiocellular carcinomas and hepatocellular nodules by combined nitrite and aminopyrine administration and Opisthorchis viverrini infection.

Combined administration of 0.1% nitrite and 0.1% aminopyrine in the drinking water for eight to ten weeks resulted in subsequent development of both hepatocellular nodules and cholangiofibrotic lesions/cholangiocellular carcinomas in Syrian golden hamsters. Additional prior dosing with Opisthorchis viverrini metacercariae (100/animal) induced inflammatory and proliferative changes in the livers of infected hamsters and was associated with a significant increase in yields of hepatocellular and cholangiocellular preneoplastic and neoplastic lesions. Thus, environmental factors thought to be casually related to the high levels of human liver cancer observed in the Northeastern provinces of Thailand were sufficient to bring about development of equivalent tumors in experimental animals. The results indicate that parasite associated liver injury and non-specific compensatory regeneration may play an important role in generation of both hepatocellular and cholangiocellular carcinomas in man.