Neoplastic transformation of mouse fibroblasts by murine sarcoma virus: a multi-step process.

Infection of cultures of three different normal rodent cell lines with murine sarcoma virus (MSV) resulted in very rapid loss of contact inhibition of growth and morphological transformation. In the case of two of these lines, anchorage dependence of growth was also rapidly lost but with the 3rd, C3H10T1/2 C1.8, an established line of mouse embryo fibroblasts, there was a delay of many cell generations before the cells became anchorage independent. This was despite 100% successful infection, as assessed by focus assays of the infected cells. The acquisition of anchorage independence was correlated with a substantial increase in tumorigenicity. A number of MSV-infected clones, isolated at random from C3H10T1/2 C1.8 cultures immediately after infection with MSV, also showed a progressive increase in anchorage independence and tumorigenicity, indicating that the progressive transformation of the uncloned cells could not be entirely due to selection of rare anchorage-independent, tumorigenic clones. It was concluded that neoplastic transformation of C3H10T1/2 C1.8 cells by MSV is a multi-step process.