Proliferation of Rous sarcoma virus-infected, but not of normal, chicken fibroblasts in a medium of reduced calcium and magnesium concentration.
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.
D001358:Avian Sarcoma Viruses; D002118:Calcium / Q000494:pharmacology*; D002413:Cations, Divalent / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects*; D002463:Cell Membrane Permeability; D002471:Cell Transformation, Neoplastic / Q000473:pathology*; D002472:Cell Transformation, Viral; D003470:Culture Media; D003593:Cytoplasm / Q000502:physiology; D008274:Magnesium / Q000494:pharmacology*; D008564:Membrane Potentials
D002413:Cations, Divalent; D003470:Culture Media; D008274:Magnesium; D002118:Calcium