The analysis of malignancy by cell fusion. VIII. Evidence for the intervention of an extra-chromosomal element.

Diploid human fibroblasts and lymphocytes were fused with the cells of a malignant mouse melanoma and a range of hybrid clones selected for study. The ability of these clones to produce progressive tumours was assayed in nude mice. Although human chromosomes were preferentially eliminated in all the hybrid clones, the human diploid cells were as effective as mouse diploid cells in suppressing the malignancy of the mouse melanoma cells. The suppression produced by fibroblasts was again more profound than that produced by lymphocytes. Malignancy was also found to be suppressed in a hybrid clone in which a single X was the only human chromosome present; and this clone continued to give a very low take incidence even after the human X had been eliminated by back selection. Hybrids were made between the melanoma cells and diploid human fibroblasts that had been given 100 J kg-1 of gamma radiation before cell fusion. These hybrids contained no recognizable human chromosomes, but their ability to produce progressive tumours was greatly reduced compared to that of the melanoma parent cells. The take incidences given by the crosses between the melanoma cells and the irradiated human fibroblasts were, however, substantially higher than those given by the crosses between the melanoma cells and unirradiated fibroblasts. These findings suggest that the suppression of malignancy involves the activity of some extra-chromosomal element and that this element is radio-sensitive.