Differences in growth factor sensitivity between individual 3T3 cells arise at high frequency: possible relevance to cell senescence.

At low serum concentrations (3% or less), individual Swiss 3T3 cells display marked heterogeneity in proliferative capacity. Here we show that this heterogeneity arises at extremely high frequency within a clone, often with sister cells showing considerable differences in capacity for further proliferation. The heterogeneity is unlikely to be due to genetic instability or mutation. Instead, it appears to reflect physiological differences between cells in their requirement for serum growth factors. It is suggested that these differences arise because cells are unable to sustain production, at low growth factor concentrations, of some rare component which is itself required for growth factor action. We believe that the generation of heterogeneity in 3T3 cells has much in common with the phenomenon of senescence in diploid cells.