Clonal Analysis of Variant Cell Lines Transformed to Malignant Cells in Tissue Culture

The following alternative interpretations of the difference between a low and high sarcoma-producing line of mouse cells derived in vitro from one cell of normal tissue origin have been examined: (1) The two lines might differ quantitatively in the proportion of malignant transplantable cells present in the cell populations. (2) Cells of the low line as compared with those of the high might possess entirely different heritable characteristics accounting for the low incidence of takes and the prolonged latent period for tumor development in vivo. A clonal analysis of the two populations has furnished evidence for the second interpretation. Five single cells from the low and high lines duplicated in their derived clones most of the characteristic properties of the line from which each originated, including the characteristic rate of tumor formation in vivo. Some differences between clones from the same line were also observed, revealing variations or potentialities for further change among individual components of the cell population. In addition, the type of culture medium was an important factor influencing the transplantability of tissue-culture cells to animals of the inbred strain of origin. The importance of transplantation for detecting the malignant conversion of cells in vitro, factors influencing the transplantability of tissue-culture cells, possible causes of the malignant transformation of cells in vitro, and interpretations of the differences between these cell lines and clones are discussed.