ABSTRACT
Immortalization of cultured cells is defined as release from cellular senescence that leads to a gradual decrease of proliferation and ultimately to cell death. Embryonic cells of different species exhibit senescence after different numbers of population doublings. The genes for T antigens of polyoma virus and of simian virus 40 have been extensively used for experimental immortalization of mammalian cells. The gene for Py large T-antigen has been shown to immortalize murine fibroblasts and epithelial cells after transfection. The Py middle T gene transforms immortalized cells to tumorigenic cells, but does not immortalize. Hybrids between normal and immortal cells exhibit limited division potential in vitro. These results indicate that the phenotype of cellular senescence is dominant, and that immortality results from recessive changes in genes involved in normal growth control. This supports the hypothesis that cellular senescence is a genetically programmed process rather than the result of random accumulation of genetic damage.
