REGULATION OF NIH-3T3 CELL G(1) PHASE TRANSIT BY SERUM DURING EXPONENTIAL-GROWTH

The proliferation rate of mammalian cells is regulated normally in the G(1) phase of the cell cycle. During this phase, it is convenient to assign positive and negative roles to the molecular programs that regu late the duration of G(1) and the phase transition from G(1) to S phas e. Density-dependent inhibition of cellular proliferation results in a n increase in the duration of G(1). This form of regulation is due to both secreted factors and cell-cell contact. Serum is mitogenic to a v ariety of mammalian cell types. Because quiescent cells enter S phase as a result of serum addition to culture media, serum is usually regar ded as a source of positive regulatory growth factors. We have measure d the length of the G(1), S and G(2)+M phases of NIH 3T3 cells during exponential growth as a function of cell density and serum concentrati on. The G(1) length increases during exponential growth as a function of density while S and G(2)+M are relatively constant. Further, this i ncrease in G(1) phase time, or density mediated negative regulation, i s inhibited by increasing serum concentration. This phenotype is satur able between 10% to 20% serum. Serum concentrations above 2.5% are abl e to increase the rate of cell cycling (decrease the G(1) phase time) by inhibiting density dependent negative regulation of NIH 3T3.