THE PROLIFERATIVE RESPONSE AND ANTIONCOGENE EXPRESSION IN OLD 2BS CELLS AFTER GROWTH-FACTOR STIMULATION

The limited replicative lifespan of diploid human cells in vitro (cell ular senescence) serves as a cellular model of aging. We examined the proliferative response of 2BS cells of different population doubling l evels to fibroblast growth factor (FGF). DNA synthesis was measured by thymidine incorporation. As the cells aged, there was a significant d ecrease in the stimulation of DNA synthesis by FGF addition (P < 0.01) . The effective concentration of FGF and the latent period prior to DN A synthesis did not change. Expression of Rb and p53 mRNA after growth factor stimulation was also examined. Young and old cells had similar Rb mRNA levels, whereas the p53 mRNA level was significantly reduced in old cells. After both cells were treated by FGF or epidermal growth factor (EGF), Rb expression increased 210-275% in young cells and 50- 60% in old ones. However, no significant change was found in p53 gene transcriptions after FGF addition. The results further suggest that ce ll aging is associated with a progressive loss of the ability of cells to respond to growth factors.