Establishment of in vivo hepatoma models in rat and mouse from rodent hepatoma cell lines.

Hepatoma is one of the most common cancers in Southeast Asia and African countries. In Taiwan, it is the leading cause of death in male cancer patients. In order to examine the effect of various factors on the growth of hepatoma, in vivo hepatoma models such as carcinogen-induced hepatoma and subcutaneous implantation of hepatoma in nude mice have been used. However, there are disadvantages in these models.Rats and mice were anesthetized by ketamine or ether, respectively. After a midline incision was made, N1S1 rat hepatoma cells were injected intrasplenically to partially hepatectomized or sham-operated rats, while BALB/c mice received intrasplenic injection of ML-2 and ML-3 mouse hepatoma cells. For direct tumor implantation, a 1mm3 N1S1 tumor piece was implanted in liver of Sprague-Dawley (SD) rat using a trocar. Animals were sacrificed at specific times after tumor implantation. Tumor incidence and the number of tumor nodules on the liver surface were recorded. Tumor samples were fixed and embedded for histological examination.After intrasplenic implantation of ML-2 cells, no tumor was observed on the liver in any of the 10 mice 40 days later. In comparison, rapid growth of hepatic ML-3 tumors was observed in all animals. Rat hepatoma cells RH-35, McA-RH7777 and McA-RH8994 cells did not form tumors in SD rats. The tumorigenicity of N1S1 cells in SD rats was dose-dependent on implanted tumor cells. In addition, hepatic N1S1 tumors could be obtained within a few weeks by homograft.We have successfully established in vivo hepatoma models in both the rat and the mouse. The murine ML-3 cells generated hepatoma in syngeneic BALB/c mice while the tumorigenicity of N1S1 cells in partially hepatectomized SD rats was dose-dependent on implanted tumor cells. These in vivo rodent models will be valuable tools for future studies of hepatoma.