Transformation of cultured rat liver cells by murine sarcoma viruses

Cultured liver cells (TRL-2 cells), originating from a BD-6 rat, an inbred black rat strain, and possessing several marker enzymes, and characteristic ultrastructures of hepatic cells, were infected with murine sarcoma viruses (MSV: Kirsten and Gazdar strains). On day 5-6 after virus inoculation, the monolayered epithelial cells focally began to pile up forming small polypoid projections, and on day 7 round-shaped cells were released from the polypoid foci. These cells first grew in a chain or as an islet of cells, but at confluent stage, they grew in suspension with some epithelioid cells attaching to the bottom of the flasks. Virus titer and focus count gave a one-hit dose response. However, 100 to 1,000 times higher titer of MSV was necessary to transform TRL-2 cells than to transform syngeneic fibroblasts, which suggested a higher repression of MSV in the epithelial cells. Those transformed TRL-2 cells showed only murine group-specific virual antigens. One of the minimal MSV-producing, MSV-transformed TRL-2 lines was subcutaneously transplanted into weanling BD-6 rats, producing progressively growing tumors with possible histology of hepatocellular carcinoma.