Mechanisms of human cell neoplastic transformation: relationship of specific abnormal clone formation to prolonged lifespan in X-irradiated human diploid fibroblasts.

A total of 9 control and 46 X-irradiated human fibroblast cultures were followed throughout their lifespan in vitro; G-banded karyotypes were examined at regular intervals. The lifespan (mean population doublings) of irradiated cultures was slightly but significantly prolonged over that of controls. None of the cultures developed any changes in cell morphology characteristic of neoplastic transformation. A number of abnormal clones containing marker chromosomes emerged in the irradiated cultures. Most of these senesced early, but 2 clones were associated with a considerably increased lifespan. One of these had a deletion in the short arm of chromosome I (p22, p32), and the other had 2 specific translocations involving chromosome 22, t(1;22)(q25,q12) and t(6;22)(p22,q11). We hypothesize that the emergence of an abnormal clone with translocations in the vicinity of critical oncogenes may be associated with prolongation of lifespan and the induction of immortalization in human diploid cells, an event independent of the acquisition of other characteristics of the transformed phenotype.