Transplantation of preneoplastic rat hepatocytes by intraportal injection.

Hepatocyte suspensions prepared from inbred male Wistar-Kyoto rats were transplanted to the livers of syngeneic recipients by injection into the portal venous system immediately after partial hepatectomy. Donor cells were labelled with 51Cr in vitro before transplantation. Animals were sacrificed 1 hr, 10 hr, 48 hr, or 1 week later and the liver radioactivity was measured in a gamma counter. Total liver radioactivity declined rapidly during the first 10 hr after transplantation, and then stabilized. After 1 week, 15-20% of the injected radioactivity still remained, indicating that this fraction of the injected cells was retained by the liver. The percentage was unaffected by the number of cells injected. In another experiment, 10(6) hepatocytes from a carcinogen-treated rat were transplanted to syngeneic rats fed 0.05% phenobarbital in the diet. Recipients developed liver carcinomas from 7 weeks after transplantation, and at 5 months 4 out of 5 animals showed severe debility and had large hepatocellular carcinomas. This model generates tumors considerably faster than those previously described, and is well suited for the study of the tumorigenic potential of subclasses of cells in liver carcinogenesis.