When Ehrlich ascites cells were fused with diploid fibroblasts, isolated directly from the animal, the resulting hybrid cells regularly produced progressive tumours. However, an analysis of a range of clonal populations of these hybrid cells, each derived from a separate primary fusion, revealed that the chromosomal constitution of these cells was highly unstable; all cell populations were found to have already undergone substantial chromosome losses by the time enough cells were available to permit chromosomal analysis. Thus, although these hybrid cells were highly tumorigenic, the tumours arising from them were not composed of cells with complete parental chromosome sets, but of cells from which some chromosomes had been eliminated.
A wide range of different kinds of malignant cell were fused with certain derivatives of the L cell line and the ability of the resulting hybrid cells to grow progressively in vivo was examined. In all cases the highly malignant character of the tumour cells was suppressed by fusion with the L cell derivatives, whether or not these had metabolic defects that facilitated selection of the hybrid cells. So long as the hybrid cells retained the complete chromosome complements of the two parent cells, their ability to grow progressively in vivo was very limited, for tumours composed of such unreduced hybrids were not found. However, when they lost certain specific, but as yet unidentified, chromosomes, the hybrid cells regained the ability to grow progressively in vivo and gave rise to a tumour. These findings thus indicated that the L cell derivatives contributed something to the hybrid that suppressed the malignancy of the tumour cell, and that this contribution was lost when certain specific chromosomes were eliminated.