AN understanding of growth control in animal cells requires an appreciation not only of cellular events important to multiplication, but also of exogenous agents which either initiate or influence the 'decisions' of a cell to reproduce. Serum has been reported to contain factors required for cell movement1, viability2, ion transport3 and control of cell density4. In addition, peptides from tissue or plasma have been identified (nerve growth factor (NGF)5, somatomedin 6, non-suppressible insulin-like activity (NSILA)7, multiplication-stimulating activity (MSA)8, epidermal growth factor9, fibroblast growth factor10) which seem to have a physiological role in the initiation of cell proliferation. Somatomedin, NSILA and MSA are probably similar, if not identical, substances and, like NGF, seem to be structurally related to insulin11-13. The ability of insulin to initiate DNA synthesis in various cells14-17 may be due to cross reactivity of the hormone with receptor sites concerned with cell multiplication12. Recent reports suggest that serum contains additional substances that can influence the ability of a cell to respond to agents which initiate DNA synthesis10,18,19. While investigating the regulatory roles of insulin and serum in the initiation of DNA synthesis in quiescent chick embryo fibroblasts (CEF), we have found a distinctive difference in the initiation capacity of these agents after the inhibition of protein synthesis. We present here evidence for the existence of a regulatory component(s) in serum which recruits cells for growth from a stage in the cell cycle position (G0?) which is refractory to mitogenic peptides.
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