Control of proliferation in two cell linesin vitro

Summary In two types of cells growing as monolayer cultures (an established line of Chinese hamster cells and a newly obtained strain of Rat Fibroblasts) no evidence is found for proliferation control by contact inhibition of mitosis or by cell-produced chemical inhibitors. Under the particular conditions of these experiments, the intracellular concentration of a multiplication-stimulating factor (MSF) associated with fetal calf serum appears to play a regulating role. This factor is degraded continually by proliferating as well as by non-proliferating, plateau phase cells. A model is proposed in which the intracellular concentration of MSF is governed by: the amount of MSF available to the cell from the culture medium; the permeability and amount of cell membrane accessible for diffusion (or transport) of MSF; and the rate of its degradation. It is hypothesized that mitosis only occurs if the concentration of MSF exceeds a critical value and that this critical value is a characteristic of the cell type. Consistency of the model with existing data concerningin vitro cell proliferation is discussed.This work was supported by Grants CA-04542 and CA-10372 from the National Cancer Institute, National Institutes of Health, U.S. Public Health Service.Biophysics trainee under United States Public Health Service Training Grant GM-00712 from the National Institutes of Health.Holder of a Dernham Senior Fellowship in Oncology from the American Cancer Society, California Division.