Woodchuck hepatocellular carcinoma has been successfully transplanted into nude (athymic) mice. The morphology of heterotransplanted tumor is similar to that of naturally occurring hepatocellular carcinoma before transplantation. The growth rate of transplanted tumor was very slow compared with those of other transplanted tumors. During the first month, only two tumors appeared. However, definitive tumor growth was noted in 6 of 20 nude mice about 3 months later. Seventeen of 20 nude mice exhibited sustained tumor growth after 6 months. The woodchuck hepatocellular carcinoma in nude mice provides an in vivo model for the study of oncogenesis of human hepatocellular carcinoma related to hepatitis B virus.
Since Snyder and Ratcliffe (1) reported the high frequency of malignant hepatoma in woodchucks, Marmota monax. The elucidation of so-called hepadnaviruses, which include hepatitis B virus (HBV), woodchuck hepatitis virus, ground squirrel hepatitis virus, and duck hepatitis virus, has progressed rapidly (2-9). Thus, the relationship between woodchuck hepatitis virus and hepatocellular carcinoma (HCC) in woodchuck has been noted, as well as the correlation of human HBV with HCC.
Accordingly, woodchuck HCC provides a superb animal model for definitive studies of HCC such as many biological problems of HCC related to hepatitis virus. Since nude (athymic) mice are particularly susceptible to a variety of transplanted tumors, we have transplanted woodchuck HCC into such animals.
Methods
Woodchuck hepatitis surface antigen ( WHsAg) was examined in the sera of 28 woodchucks purchased from the International Animal Exchange Inc. (Michigan). The Austria I1 radioimmunoassay method (Dainabot Radioisotope Laboratory, Co. Ltd., Tokyo, Japan) was employed, and depended on the cross-reactivity between WHsAg