The Journal of Membrane Biology

, Volume 26, Issue 1, pp 19–30 | Cite as

Control of the uptake of amino acids by serum in chick embryo cells, untransformed or transformed with rous sarcoma virus

  • P. M. Bhargava
  • P. Vigier


Forty to fifty minutes after removal of serum, the net total uptake of amino acids in growing secondary cultures of normal or virus-transformed chick embryo cells, stopped or proceeded only at a highly reduced rate. In both normal and transformed cells, theinitial (0–40 min) rate of the above uptake was the same in the absence of serum as in its presence. The initial rate of the total uptake of amino acids in growing transformed cells was about the same as in growing normal cells. Neither in the normal nor in the transformed cells was the rate of the total uptake of amino acids reduced by cell confluence alone. In highly dense, hyperconfluent cultures of normal cells in which cell growth was arrested, the rate of uptake in the absence or in the presence of serum was four- to fivefold lower than the rate obtained in growing normal cells under similar conditions; in the absence of serum, the net uptake stopped after 40 min in the hyperconfluent cultures as well. It appears that cells growing in tissue culture require a serum factor for maintenance of the required high rates of uptake of amino acids and that the inhibition of growth at high cell densities is a result of depletion of this factor from serum, or the inability of the cells in a dense culture to respond to the factor. A serum factor is apparently also required for maintenance of the reduced rates of uptake of amino acids observed in hyperconfluent cultures.


Cell Growth Tissue Culture Sarcoma Cell Density Human Physiology 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Adamson, L.P., Herington, A.G., Bornstein, J. 1972. Evidence for the selection by the membrane transport system of intracellular or extracellular aminoacids for protein synthesis.Biochim. Biophys. Acta 282:352PubMedGoogle Scholar
  2. 2.
    Averdunk, R. 1972. The effect of phytohaemagglutinin and antilymphocyte serum on the transport of potassium ions, glucose and aminoacids in human lymphocytes.Hoppe-Seyler's Z. Physiol. Chem. 353:79PubMedGoogle Scholar
  3. 3.
    Bhargava, P.M., Allin, E.P., Montagnier, L. 1976. Uptake of amino acids and thymidine during the first cell cycle of synchronized hamster cells.J. Membrane Biol. 26:1Google Scholar
  4. 4.
    Bhargava, P.M., Siddiqui, M.A., Kumar, G.K., Prasad, K.S.N. 1975. Effect of cell concentration on the uptake of amino acids by rat liver parenchymal cells in suspension.J. Membrane Biol. 22:357Google Scholar
  5. 5.
    Bhargava, P.M., Szafarz, D., Bornecque, C.A., Zajdela, F. 1976. A comparison of the ability of normal liver, a premalignant liver, a solid hepatoma and the Zajdela ascitic hepatoma, to take up amino acidsin vitro.J. Membrane Biol. 26:31Google Scholar
  6. 6.
    Biquard, J.M., Vigier, P. 1972. Characteristics of a conditional mutant of Rous sarcoma virus defective in ability to transform cells at high temperature.Virology 47:444PubMedGoogle Scholar
  7. 7.
    Burger, M.M. 1971. Cell surfaces in neoplastic transformation.Curr. Top. Cell. Regul. 3:135Google Scholar
  8. 8.
    Christensen, H.N., Rothwell, J.T., Sears, R.A., Streicher, J.A. 1948. Association between rapid growth and elevated cell concentrations of amino-acids. II. In regenerating liver after partial hepatectomy in the rat.J. Biol. Chem. 175:101Google Scholar
  9. 9.
    Clarke, G.D., Stoker, M.G.P., Ludlow, A., Thornton, M. 1970. Requirement of serum for DNA synthesis in BHK 21 cells; effects of density, suspension and virus transformation.Nature 227:798PubMedGoogle Scholar
  10. 10.
    Colby, C., Rubin, H. 1969. Growth and nucleic acid synthesis in normal cells and cells infected with Rous sarcoma virus.J. Nat. Cancer Inst. 43:437PubMedGoogle Scholar
  11. 11.
    Cunningham, D.D. 1972. Changes in phospholipid turnover following growth of 3T3 mouse cells to confluency.J. Biol. Chem. 247:2464PubMedGoogle Scholar
  12. 12.
    Cunningham, D.D., Pardee, A.B. 1969. Transport changes rapidly initiated by serum addition to “contact inhibited” 3T3 cells.Proc. Nat. Acad. Sci. USA 64:1049PubMedGoogle Scholar
  13. 13.
    Cunningham, D.D., Pardee, A.B. 1971. Transport and phospholipid change related to control of growth in 3T3 cells.In: Growth Control in Cell Cultures. G.E.W. Wolstenholme and J. Knight, editors. p. 207. Churchill Livingstone, LondonGoogle Scholar
  14. 14.
    Foster, D.O., Pardee, A.B. 1969. Transport of aminoacids by confluent and non-confluent 3T3 and polyoma virus-transformed 3T3 cells growing on glass cover slips.J. Biol. Chem. 244:2675PubMedGoogle Scholar
  15. 15.
    Golde, A., Vigier, P. 1961. Growth of Rous sarcoma virus and cells in non-confluent chick embryo monolayers.Virology 15:36PubMedGoogle Scholar
  16. 16.
    Golde, A., Villaudy, J. 1972. The effect of ageing and cell density on the infection and the morphological conversionin vitro by Rous sarcoma virus of chick embryo fibroblasts.In: The Biology of Oncogenic Viruses, Proc. 2nd Lepetit Colloquium, Paris, 1972. L. Silvestri, editor. p. 124. North-Holland Publ. Co., AmsterdamGoogle Scholar
  17. 17.
    Goldfine, I.D., Gardner, J.D., Neville, D.M. 1972. Insulin action in isolated rat thymocytes.J. Biol. Chem. 247:6919PubMedGoogle Scholar
  18. 18.
    Griffiths, J.B. 1972. Role of serum, insulin and aminoacid concentration in contact inhibition of growth of human cells in culture.Exp. Cell. Res. 75:47PubMedGoogle Scholar
  19. 19.
    Hare, J.D. 1967. Location and characteristics of the phenylalanine transport mechanism in normal and polyoma-transformed hamster cells.Cancer Res. 27:2357PubMedGoogle Scholar
  20. 20.
    Hare, J.D. 1970. Quantitative aspects of thymidine uptake into the acid-soluble pool of normal and polyoma-transformed hamster cells.Cancer Res. 30:684PubMedGoogle Scholar
  21. 21.
    Hare, J.D. 1972. A labile, serum-dependent uridine uptake function in mouse embryo cells.Biochim. Biophys. Acta 282:401PubMedGoogle Scholar
  22. 22.
    Hatanaka, M., Hanafusa, H. 1970. Analysis of a functional change in membrane in the process of cell transformation by Rous sarcoma virus; alteration in the characteristics of sugar transport.Virology 41:647PubMedGoogle Scholar
  23. 23.
    Hershko, A., Mamont, P., Shields, R., Tomkims, G.M. 1971. Hypothesis relating growth regulation in mammalian cells to stringent controls in bacteria.Nature, New Biol. 232:206Google Scholar
  24. 24.
    Holley, R.W., Kiernan, J.A. 1968. Contact inhibition of cell division in 3T3 cells.Proc. Nat. Acad. Sci. USA 60:300PubMedGoogle Scholar
  25. 25.
    Kay, J.F. 1972. Lymphocyte stimulation by phytohaemagglutinin: Role of the early stimulation of potassium uptake.Exp. Cell. Res. 71:245PubMedGoogle Scholar
  26. 26.
    Leffert, H.L., Paul, D. 1973. Serum dependent growth of primary cultured differentiated foetal rat hepatocytes in arginine-deficient medium.J. Cell. Physiol. 81:113PubMedGoogle Scholar
  27. 27.
    Levine, E.M., Becker, Y., Boone, C.W., Eagle, H. 1965. Contact inhibition, macromolecular synthesis and polyribosomes in cultured diploid fibroblasts.Proc. Nat. Acad. Sci. USA 53:350PubMedGoogle Scholar
  28. 28.
    Stoker, M.G.P. 1973. Role of diffusion boundary layer in contact inhibition of growth.Nature 246:200PubMedGoogle Scholar
  29. 29.
    Temin, H.M. 1966. Studies on carcinogenesis by avian sarcoma viruses. III. The differential effect of serum and polyanions on multiplication of uninfected and converted cells.J. Nat. Cancer Inst. 37:167PubMedGoogle Scholar
  30. 30.
    Temin, H.M., Pierson, R.W., Jr., Dulak, J.C. 1972. The role of serum in the control of multiplication of avian and mammalian cells in culture.In: Growth, Nutrition and Metabolism of Cells in Culture. G.H. Rothblat and J.J. Cristofalo, editors. p. 50. Academic Press, New York & LondonGoogle Scholar
  31. 31.
    VanDenBerg, K.J., Betel, I. 1973. Increased transport of 2-aminobutyric acid in rat lymphocytes stimulated with Concanavalin A.Exp. Cell. Res. 76:63PubMedGoogle Scholar
  32. 32.
    VanDenBerg, K.J., Betel, I. 1973. Selective early activation of a sodium-dependent aminoacid transport system in stimulated rat lymphocytes.FEBS Lett. 29:149PubMedGoogle Scholar
  33. 33.
    Waller, J.M., Kirsten, W.M. 1970. Density-dependent inhibition of protein synthesis in normal and virus-transformed cells.Virchows Arch. 6:183Google Scholar
  34. 34.
    Weber, M.J., Edlin, G. 1971. Phosphate transport, nucleotide pools and ribonucleic acid synthesis in growing and in density-inhibited 3T3 cells.J. Biol. Chem. 246:1828PubMedGoogle Scholar
  35. 35.
    Weber, M.J., Rubin, H. 1971. Uridine transport and RNA synthesis in growing and in density-inhibited animal cells.J. Cell. Physiol. 77:157PubMedGoogle Scholar
  36. 36.
    Whitney, R.B., Sutherland, R.M. 1973. Effects of chelating agents on the initial interaction of phytohaemagglutinin with lymphocytes and the subsequent stimulation of aminoacid uptake.Biochim. Biophys. Acta 228:790Google Scholar

Copyright information

© Springer-Verlag New York Inc. 1976

Authors and Affiliations

  • P. M. Bhargava
    • 1
  • P. Vigier
    • 1
  1. 1.Section de BiologieInstitut du RadiumOrsayFrance

Personalised recommendations