Growth regulation and tumour formation of normal and neoplastic rat cells.

Abstract

AbstractThe oncogenicity of cells in syngeneic hosts was compared to the regulation of cell growth in vitro. Normal embryonic fibroblasts (LWF cells) were not tumorigenic. Spontaneously “transformed” fibroblastic cells (LW13 cells) and Rous‐transformed epithelioid cells (RsK4 cells) grew into sarcomas on subcutaneous or intravenous inoculation. TD50 varied according to the route of administration and dispersion of the cells. Rous‐transformed cells gave rise to tumours with a short latent period while the spontaneously transformed cell line showed a biphasic latent period. The histopathology of the two kinds of tumours was similar, with a higher tendency to pleomorphism in the Rous tumours. Normal fibroblasts had low plating efficiency on plastic or in soft gel suspension. LW13 cells plated with high efficiency on plastic but poorly in suspension, and RsK4 cells plated with high efficiency in both situations. Normal cells were highly sensitive to topoinhibition, LW13 cells were moderately sensitive, while LW13 cells explanted from tumours and RsK4 cells were the least sensitive. However, values of topoinhibition and its compensation by serum were themselves found to vary with cell density. RsK4 cells initiated DNA synthesis in low serum medium but normal cells and LW13 cells did not. Neither LW13 nor RsK4 cell proliferation was inhibited by contact with confluent, static 3T3 cells or normal LWF cells. With the cell types examined here an association exists between contact inhibition of cell movement and topoinhibition of growth. The degree to which altered cells respond to the regulatory contact signals of normal cells appears to be the best in vitro indicator of oncogenicity.