GENETIC-ANALYSIS OF INDEFINITE DIVISION IN HUMAN-CELLS - EVIDENCE FORA COMMON IMMORTALIZING MECHANISM IN T-LYMPHOID AND B-LYMPHOID CELL LINES

Somatic cell hybrids are useful for gaining insight into the process(e s) by which normal human cells undergo senescence. In previous studies , we found that hybrids generated by fusing normal human diploid fibro blasts, T lymphocytes, and endothelial cells with various immortal hum an cell lines exhibited limited division potential. This leads to the conclusion that the phenotype of cellular senescence is dominant and t hat immortal cells arise due to recessive changes in normal growth con trol mechanisms. Fusion of over 30 immortal cell lines led to the iden tification of four complementation groups for indefinite division. The se data suggest that unlimited division potential can result from chan ges in at least four different genes or pathways. Complementation grou p assignment did not correlate with cell type, tumor type, embryonal l ayer of origin, or expression of an activated oncogene. The focus of t his study was to determine the complementation group(s) to which vario us human lymphoblastoid cells assign so as to better understand the me chanism(s) by which these cell types undergo cellular senescence and i mmortalization. Seven lymphoid cell lines were studied and assigned to a single complementation group. This result supports the hypothesis t hat T and B cells undergo senescence by mechanisms similar to those oc curring in fibroblasts and endothelial cells and provides evidence for a common mechanism(s) involving a senescence-related gene(s) for immo rtalization of these immune system derived cell lines. (c) 1994 Academ ic Press, Inc.