APPARENT DESENSITIZATION OF SWISS 3T3 CELLS TO THE MITOGENS FGF AND VASOPRESSIN

The growth factors FGF [fibroblast growth factor] and vasopressin have only a transient effect on confluent quiescent monolayers of Swiss 3T3 cells. Whether measured as cumulative entry into S-phase by autoradiography, or as cell division by time-lapse filming, the elevated rate of cell proliferation was maintained only over 10-15 h. Several trivial or artifactual explanations for this transience were ruled out, including toxicity of 3H-thymidine; exhaustion or degradation or medium components, nutrients or growth factors (although some medium depletion was observed); and the generation during quiescence of cells incapable of division. Heritable variation in the capacity to respond to individual growth factors was eliminated. However, unstable phenotypic heterogeneity in growth factor requirements between cells may play some part, as found elsewhere for the response to low concentrations of serum (Brooks et al.). Cell populations that had ceased to respond to vasopressin recovered their sensitivity after 2-3 days incubation in conditioned medium lacking vasopressin. The phenomenon thus resembles the mitogen-induced desensitization described by Collins and Rosengurt. However, in our case, the loss of sensitivity was not selective for vasopressin but applied also to epidermal growth factor (EGF) and to prostaglandin F2. Changes in responsiveness to vasopressin with time were associated with changes in cell density. Although some element of selective desensitization has not been ruled out, the transient response in our experiments can be accounted for in terms of unstable heterogeneity in growth factor requirements and/or in terms of density-dependent regulation of growth.