Progressive loss of the proliferative response of senescing WI-38 cells to platelet-derived growth factor, epidermal growth factor, insulin, transferrin, and dexamethasone.

Normal human diploid cell lines such as WI-38 display a progressive loss of responsiveness to the mitogenic components in serum. Using a serum-free, hormone-growth factor supplemented medium for WI-38 cells (Phillips & Cristofalo, 1980, 1981), we examined the dose-response relationships of cells to the individual growth factor at various in vitro ages. Although as cultures senesced, they became progressively less responsive to mitogenic stimulation, the concentration of epidermal growth factor (25 ng/ml), insulin (5 micrograms/ml), transferrin (5 micrograms/ml), and dexamethasone (55 ng/ml) that elicited the maximum proliferative response did not change as a function of age. As cultures age they may require increasing amounts of platelet-derived growth factor to elicit the maximum mitogenic response.