ABSTRACT
In the presence of growth factors, young cells will initiate the events which lead to DNA replication and then replicate the DNA, while senescent cells, although carrying out some G1 events, do not synthesize DNA. In this chapter, the authors examine some of our recent work focusing on growth factor responsiveness and various aspects of growth factor-cell interactions throughout the proliferative life span of WI-38 cells. When cultures were treated with indomethacin to inhibit the enzyme cyclo-oxygenase and prevent the conversion of arachidonic acid (AA) into prostaglandins (PGs), the release of A A from young cells was stimulated threefold, to a rate similar to that seen with untreated senescent cells. Taken together, findings suggest an altered regulation of AA metabolism in late-passage cells. Under the serum-free conditions of our experiments, senescent cells elaborate substantially more PGE2 than do young cells, and the concentrations achieved (approximately 0.3 ng/ml) are in the range of the effective concentrations for the inhibition of growth of early-passage cells.
