The ability of normal mouse cells to reduce the malignant potential of transformed mouse bladder epithelial cells depends on their somatic origin

Somatic cell hybrids have been made between a transformed mouse bladder carcinoma cell line and normal mouse bladder epithelium and mesenchyme. In the epithelial tumour/mesenchyme hybrids the malignant phenotype was expressed dominantly whereas in the carcinoma/normal epithelium hybrids the malignant potential was greatly reduced. In both cases the dominant in vitro and in vivo phenotype was that of the normal parental cells. All hybrid tumours were first palpable after 4–7 days, demonstrating that the tumours had not arisen as a result of in vivo selection of a sub‐population of tumorigenic cells. Chromosome analysis showed that the carcinoma/normal epithelium hybrids were all in the hypertetraploid range but the large variation in the karyotypic profile of each hybrid made it impossible to implicate any specific chromosomes in the control of expression of the malignant phenotype. During normal development in bladder epithelium, terminal differentiation is associated with tetraploid formation by cell fusion. The reduction in malignancy of the carcinoma/normal epithelium hybrids may perhaps be due to the expression of genes associated with normal terminal differentiation after cell fusion and tetraploid formation. This is also supported by the more differentiated phenotype of the hybrid tumours. Of the 10 mesenchyme/epithelium hybrids analysed cytotogenetically, four were in the hypertetraploid range from which little meaningful data could be obtained about specific chromosome losses. Chromosome analysis of the cells from the near‐tetraploid hybrids showed only minor differences from what might have been expected from the input of the two parents; these differences appeared to be due to random chromosome loss. The maximum number of chromosomes lost from any of the hybrids was five, although one, two or three was more usual. The only consistent chromosome loss was of a single copy of chromosome 4, which in two of the hybrids represented the only chromosome change. The possibility that this loss might facilitate re‐expression of the malignant phenotype is discussed.