Apparent desensitization of Swiss 3T3 cells to the mitogens FGF and vasopressin.
The growth factors FGF and vasopressin were found to 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 hr. Several trivial or artifactual explanations for this transience were ruled out, including toxicity of 3H-thymidine; exhaustion or degradation of medium components, nutrients or growth factors (although some medium depletion was observed); and the generation during quiescence of cells incapable of division. We have also eliminated heritable variation in the capacity to respond to individual growth factors. 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, 1984). 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 (1982, 1983). 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 alpha. Furthermore, 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.
D000818:Animals; D002455:Cell Division / Q000187:drug effects*; D002460:Cell Line; D002470:Cell Survival; D003470:Culture Media / Q000494:pharmacology; D015237:Dinoprost; D004351:Drug Resistance; D004815:Epidermal Growth Factor / Q000494:pharmacology; D005346:Fibroblast Growth Factors / Q000378:metabolism / Q000494:pharmacology*; D051379:Mice; D008815:Mice, Inbred Strains; D011460:Prostaglandins F / Q000494:pharmacology; D014667:Vasopressins / Q000494:pharmacology*
D003470:Culture Media; D011460:Prostaglandins F; D014667:Vasopressins; D005346:Fibroblast Growth Factors; D004815:Epidermal Growth Factor; D015237:Dinoprost