Suppression of the transformed phenotype in somatic cell hybrids

Somatic cell hybrids between mouse mammary tumour cells (TA3B) and diploid rat embryo fibroblasts (REF) or between TA3B and Syrian hamster sarcoma cells (BI) were examined for the in vitro characteristics of transformed cells as soon as possible after cell fusion. Unlike the parental tumour cells as three of four TA3B X REF and five BI X TA3B independent hybrid lines had low colony-forming efficiencies in agar, exhibited density-dependent inhibition of growth and did not form colonies on confluent monolayers of 3T3 cells, demonstrating that the transformed phenotype was suppressed in these hybrids. In addition tests of some of the hybrid lines for tumour production in nude mice showed that this was also suppressed. Suppression was more stable in the TA3B X REF than in the BI X TA3B hybrids, variants of the BI X TA3B hybrids with the properties of transformed cells could be readily isolated by subculturing cells that had grown in agar. Tumour growth selected for hybrids with the characteristics of transformed cells, and derivatives of the hybrids selected to show the transformed phenotype readily produced tumours. These correlations suggest that the transformed phenotype and malignancy may be under the same control in these cells. The phenomenon of suppression may be explained by the hypothesis that neoplastic transformation results from recessive mutations in genes which control the normal phenotype. On this model the finding of suppression in hybrids between two different tumour lines is interpreted as complementation and indicates that the mutations are not the same in all cell lines.