AbstractWhen quiescent cells in monolayer culture are stimulated to proliferate with growth factor, the entry into S‐phase or mitosis appears to follow first‐order kinetics, with a probability to enter the cell cycle that depends on growth factor concentration (Smith and Martin, 1973). Suboptimal growth factor concentrations also lead to a decreased fraction of the cell population that responds to the stimulation (Brooks et al., 1984). Using flow cytometry, we have re‐investigated this dual effect of growth factor concentration on cultures of quiescent normal human skin fibroblasts, stimulated with submaximal concentrations of fetal calf serum, epidermal growth factor, and platelet‐derived growth factor. The size of the responding population decreased with decreasing concentration of growth factor, but the time course of cell division within this responding population was identical for all growth factor concentrations. This is in conflict with previous concepts and indicates that the entry into the proliferative state is based on a decision mechanism that cannot be adequately described using transition probabilities determined by mitogen concen
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