High frequency of tumour cell reversion to non-tumorigenic phenotype

Nine spontaneously transformed cell lines were isolated from embryo fibroblasts of mice and rats with different genotypes. In six cell lines highly tumorigenic cell variants were selected. At the start of culture all cell lines were of low or zero tumorigenicity. The same cells in a confluent monolayer in vitro had high contact inhibition of growth and proliferated in response to stimulation by growth factors. Tumour progression of the established lines was accompanied by significant changes of these properties. Clonal analysis of the six most malignant cell lines revealed their capacity to revert simultaneously to the non-tumorigenic state and to their initial growth characteristics. Frequencies of reversion to the non-tumorigenic phenotype were much higher than re-reversion to the tumorigenic phenotype. The reversions occurred in several sequential passages of transformed clones, with some variations in individual clones. These observations suppose that frequencies of tumour reversions are a constant genetic characteristic of every cell line.