Modulation of the platelet-derived growth factor induced replicative response.

Quiescent cultures of density arrested BALB/c-3T3 cells have been sensitized to the growth stimulatory action of the platelet-derived growth factor (PDGF). Sensitization was achieved by depriving the cultures of PDGF prior to growth stimulation and was noted after transfer of cultures from medium supplemented with 10% serum to medium containing either an equivalent concentration of platelet-poor plasma or a low concentration (0.5%) of serum. Sensitized cultures required less pure PDGF for growth stimulation than nonsensitized ones. In addition such cultures required less mitogen to synthesize a PDGF modulated major excreted protein (MEP). The mechanism of sensitization was investigated. Sensitized cultures did not bind more PDGF than non-sensitized ones. Rather, sensitization appeared to result from the loss of cells that occurred when cultures were deprived of PDGF. Such a loss increased the amount of PDGF available per cell, causing a higher percentage of cells to enter the S phase. Similarly, the amount of PDGF per cell regulated MEP synthesis. Furthermore, in non-sensitized cultures (containing the same number of cells), the absolute quantity rather than the concentration of PDGF regulated DNA synthesis. It appears that the amount of PDGF per cell modulates mitogenesis.