Dominance of In Vitro Senescence in Somatic Cell Hybridization and Biochemical Experiments

Abstract

Studies reported here have led us to conclude that both senescent and quiescent cells produce a protein(s) inhibitor that blocks the initiation of DNA synthesis. In quiescent cells the inhibitor is rapidly lost after the addition of growth factors, whereas in senescent cells the inhibitor is produced even in the presence of serum growth factors. In a further series of experiments we have found that the phenotype of finite proliferative lifespan is dominant in somatic cell hybrids between normal human cells and immortal cells and, in addition, that fusion of certain immortal cell lines with other immortal cell lines yield hybrids with finite proliferative lifespan. These results suggest that in vitro cellular senescence results from a genetic program that causes a potent inhibitor of DNA synthesis to be produced at the end of the in vitro lifespan, and that immortal cells arise as a result of recessive changes in this program.