Proliferation of Rous Sarcoma Virus-Infected, but not of Normal, Chicken Fibroblasts in a Medium of Reduced Calcium and Magnesium Concentration

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 76; no. 8; pp. 3913 - 3916
• Main Authors: Balk, Samuel D., Polimeni, Philip I., Hoon, Baldev Singh, LeStourgeon, Dana N., Mitchell, Richard S.
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences of the United States of America 01-08-1979; National Acad Sciences
• Subjects: Avian Sarcoma Viruses; Biological Sciences: Cell Biology; Blood plasma; Calcium; Calcium - pharmacology; Cations, Divalent - metabolism; Cell Division - drug effects; Cell growth; Cell Membrane Permeability; Cell membranes; Cell Transformation, Neoplastic - pathology; Cell Transformation, Viral; Cells; Culture Media; Cytoplasm - physiology; Divalent cations; Fibroblasts; Magnesium; Magnesium - pharmacology; Membrane Potentials; Sarcoma; Viruses
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.76.8.3913

Both normal and Rous sarcoma virus-infected chicken fibroblasts proliferate actively in a culture medium containing physiological concentrations of calcium (1.2 mM) and magnesium (0.7 mM). In the presence of a physiological concentration of magnesium, reduction of the calcium concentration to 0.125 mM resulted in a significant decrease in the proliferation of the normal, but not of the neoplastic, fibroblasts. Reduction of the magnesium concentration to 0.05 mM in the presence of a physiological concentration of calcium had a similar effect. In a culture medium containing reduced concentrations of both calcium (0.20 mM) and magnesium (0.05 mM), the normal fibroblasts were maintained without proliferation, whereas the Rous sarcoma virus-infected fibroblasts continued to proliferate actively. The cytosol concentrations of ionized calcium and magnesium are known to be regulated by a balance between net passive influx and active extrusion and sequestration. On the basis of this consideration and the findings described above it can be hypothesized that: (i) Fibroblast replication is initiated when cytosolic concentrations of calcium, magnesium, or both rise above a critical level. (ii) Autonomous initiation of replication of neoplastic fibroblasts is a result of failure of cytoplasmic divalent cation homeostasis; alternatively, sarcoma virus infection may endow cells with a divalent cation-independent mechanism that bypasses an initiation mechanism that is, normally, divalent cation-dependent. (iii) Proliferation of normal fibroblasts is controlled by extracellular matrix components that interact with cell surfaces in a manner that limits the permeability of plasma membranes to divalent cations or otherwise functions to lower cytosol divalent cation concentrations.