Induction of the transformed phenotype in tissue culture cells by transfection with DNA from human brain tumors.
The DNA from 14 human brain tumors was used for transfection of recipient primate, bovine, and murine tissue culture cells. Only CV-1 cells responded to transfection with the acquisition of the transformed phenotype as determined by colony formation in medium with a low serum content. With the DNA derived from four tumors, transformation of recipient CV-1 cells was achieved, and the transformed phenotype remained stably expressed over numerous passages. Two out of these four tumors were shown to contain episomal noninfectious SV40 genomes. In at least one case, it was possible to demonstrate the transfer of the SV40 episomes into the CV-1 cells. After 10 passages of the clonal transformed CV-1 cells, the episomes were apparently lost, yet the cells retained the transformed phenotype. Thus, the SV40 episomes were not required for the maintenance of the transformed state. Their etiological role in the human brain tumors remains, nevertheless, in our opinion, obscure. We are currently trying to amplify the SV40 episomes by molecular cloning in order to further assess their biological properties. Furthermore, attempts will be made to identify the DNA sequences which are responsible for transformation of the CV-1 cells according to the protocols that were applied recently for the isolation of human transforming genes [5-7].