The analysis of malignancy by cell fusion. V. Further evidence of the ability of normal diploid cells to suppress malignancy.

INTRODUCTION We have presented a substantial body of experiment to show that when cells from a range of different highly malignant mouse tumours are fused with cells of low tumorigenicity, the malignant phenotype is suppressed in the hybrid cell (Harris, Miller, Klein, Worst & Tachibana, 1969; Klein, Bregula, Wiener & Harris, 1971; Harris, 1971). The most decisive results were obtained with hybrid cells produced by the fusion of the tumour cells with cells of the A 9 line, an L cell derivative of low tumorigenicity (Klein et al. 1971). Suppression of malignancy could also be demonstrated in hybrid cells produced by fusing tumour cells with diploid fibroblasts, but, in the latter case, the chromosomal constitution of the hybrid cells was characterized by pronounced instability so that a wide spectrum of genetically disparate hybrid populations was generated. This variation was reflected in the take incidence when different clonal populations were tested: some hybrid clones showed very little ability to grow progressively in vivo, others produced tumours readily (Wiener, Klein & Harris, 1971; Klein, Friberg, Wiener & Harris, 1973). We now provide clearer evidence of the ability of normal diploid cells to suppress malignancy. The malignant cells used in the present study were those of the A9HT line, a highly tumorigenic L cell derivative selected from the wild type A 9 line by passage through the animal (Wiener, Klein & Harris, 1973). The A9HT cells were fused with normal diploid mouse lymphocytes and the tumorigenicity of a range of clonal hybrid cell populations, each derived from a separate primary fusion, was tested. The results could be compared with those previously obtained with hybrids produced by fusing A9HT with cells of a malignant