Biological Trace Element Research

, Volume 1, Issue 2, pp 87–100 | Cite as

Control of Ehrlich cell division by zinc

  • David H. Petering
  • Leon A. Saryan


The nutritional requirement for zinc in the proliferation of normal and malignant cells has been demonstrated in a number of animal studies. A distinction is made between the effect of zinc status upon the host during carcinogenesis and tumor growth. The present studies focus on the Ehrlich ascites tumor in mice fed a semipurified zinc-deficient diet along with defined concentration of zinc in the drinking water. This model of zinc deficiency is compared with others in which chelating agents are used to create zinc-deficient conditions or the microorganismEuglena gracilis is examined in a defined zinc-deficient medium. It is reported here that Ehrlich cells remain quiescent for several weeks in severely deficient mice, suggesting their restriction to a G1 or G0 state of the cell cycle. The kinetics of thymidine and uridine uptake and incorporation into DNA and RNA in Zn-normal and Zn-deficient tumors is consistent with the inhibition of thymidine kinase and DNA polymerase in the Zn-deprived system, but with little effect on RNA synthesis. The concentration of metabolites of these labeled nucleosides in Ehrlich cells is also consistent with a primary effect upon thymidine kinase. Although the ascites fluid Zn is depressed in Zn deficiency, total cellular zinc and its distribution among cell fractions is not significantly affected. It is suggested that these effects are specific in nature and not the result of a general lack of zinc for zinc metalloproteins and other binding sites in the cell.

Key Words

Zinc, cell division control by DNA synthesis, control by zinc RNA synthesis, control by zinc Ehrlich cells, zinc control of cell division 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    L. Foulds,Neoplastic Development, Vol. 1, Academic Press, New York, 1969.Google Scholar
  2. 2.
    D. E. Poswillo and B. Cohen,Nature 231, 447 (1971).PubMedCrossRefGoogle Scholar
  3. 3.
    J. R. Duncan and I. E. Dreosti,J. Natl. Cancer Inst. 55, 195 (1975).PubMedGoogle Scholar
  4. 4.
    L. Y. Y. Fong, A. Sivak, and P. M. Newberne,J. Natl. Cancer Inst. 61, 145 (1978).PubMedGoogle Scholar
  5. 5.
    P. J. Fraker, S. M. Haas, and R. W. Luecke,J. Nutr. 107, 1889 (1977).PubMedGoogle Scholar
  6. 6.
    P. Frost, J. C. Chen, I. Robbini, J. Smith, and A. Prasad, inZinc Metabolism: Current Aspects in Health and Disease, Liss, 1977, pp. 143–150.Google Scholar
  7. 7.
    T. Tanako, G. Fernandes, C. Tsao, K. Pih, and R. A. Good,Fed. Proc. 37, 931 (1978).Google Scholar
  8. 8.
    M. B. Sporn, N. M. Dunlop, D. L. Newton, and J. M. Smith,Fed. Proc. 35, 1332 (1976).PubMedGoogle Scholar
  9. 9.
    J. C. Smith, Jr., E. G. McDaniel, F. F. Fau, and J. A. Halsted,Science 181, 954 (1973).PubMedCrossRefGoogle Scholar
  10. 10.
    H. G. Petering, H. H. Buskirk, and J. A. Crim,Cancer Res. 27, 1115 (1967).PubMedGoogle Scholar
  11. 11.
    W. DeWys, W. J. Pories, M. C. Richter, and W. H. Stain,Proc. Soc. Expl. Biol. Med. 135, 17 (1970).Google Scholar
  12. 12.
    J. T. McQuitty, Jr., W. D. DeWys, L. Monaco, W. H. Stain, C. G. Rob, J. Apgar, and W. J. Pories,Cancer Res. 30, 1387 (1970).PubMedGoogle Scholar
  13. 13.
    W. DeWys and W. Pories,J. Natl. Cancer Inst. 48, 375 (1972).PubMedGoogle Scholar
  14. 14.
    D. H. Barr and J. W. Harris,Proc. Soc. Expl. Biol. Med. 144, 284 (1973).Google Scholar
  15. 15.
    D. Minkel, P. T. Dolhun, B. L. Calhoun, L. A. Saryan, and D. H. Petering,Cancer Res. in press (1979).Google Scholar
  16. 16.
    L. A. Saryan, D. T. Minkel, P. J. Dolhun, B. L. Calhoun, S. Wielgus, M. Schaller, and D. H. Petering,Cancer Res. in press (1979).Google Scholar
  17. 17.
    H. H. Sandstead and R. A. Rinaldi,J. Cell Physiol. 73, 81 (1969).PubMedCrossRefGoogle Scholar
  18. 18.
    H. Swenerton, R. Shrader, and L. S. Hurley,Science 166, 1014 (1969).PubMedCrossRefGoogle Scholar
  19. 19.
    J. M. Hsu and W. L. Anthony,Clin. Chem. 21, 544 (1975).PubMedGoogle Scholar
  20. 20.
    A. S. Prasad and D. Oberleas,J. Lab. Clin. Med. 83, 634 (1974).PubMedGoogle Scholar
  21. 21.
    I. E. Dreosti and L. S. Hurley,Proc. Soc. Expl. Biol. Med. 150, 161 (1975).Google Scholar
  22. 22.
    J. R. Duncan and I. E. Dreosti,South African Med. J.,50, 711 (1976).Google Scholar
  23. 23.
    I. Lieberman, R. Abrahms, N. Hunt, and P. Ove,J. Biol. Chem. 238, 3955 (1963).PubMedGoogle Scholar
  24. 24.
    M. Fujioka and I. Lieberman,J. Biol. Chem. 239, 1164 (1964).PubMedGoogle Scholar
  25. 25.
    J. K. Chesters,Biochem. J. 130, 133 (1972).PubMedGoogle Scholar
  26. 26.
    J. K. Chesters,Biochem. J. 150, 211 (1975).PubMedGoogle Scholar
  27. 27.
    J. K. Chesters, inTrace Element Metabolism in Animals, W. G. Hoekstra, J. W. Suttie, H. E. Ganther, and W. Mertz, eds., University Park Press, Baltimore, Vol. 2, 1974, pp. 39–50.Google Scholar
  28. 28.
    R. O. Williams and L. A. Loeb,J. Cell. Biol. 58, 594 (1973).PubMedCrossRefGoogle Scholar
  29. 29.
    K. H. Falchuk and A. Krishan,Cancer Res. 37, 2050 (1977).PubMedGoogle Scholar
  30. 30.
    L. G. Sillen and A. E. Martell,Stability Constants of Metal Ion Complexes, The Chemical Society, Burlington House, London, 1964.Google Scholar
  31. 31.
    E. Robbino and T. Pederson,Proc. Natl. Acad. Sci. U.S.A. 66, 1244 (1970).CrossRefGoogle Scholar
  32. 32.
    J. A. Fernandez-Pol,Biochem. Biophys. Res. Commun. 78, 136 (1977).PubMedCrossRefGoogle Scholar
  33. 33.
    V. D’Aurora, A. M. Stern, and D. S. Sigman,Biochem. Biophys. Res. Commun. 80, 1025 (1978).PubMedCrossRefGoogle Scholar
  34. 34.
    D. H. Petering, inInorganic and Nutritional Aspects of Cancer, G. N. Schrauzer, ed., Plenum, New York, 1977, pp. 179–191.Google Scholar
  35. 35.
    K. H. Falchuk, A. Krishan, and B. L. Vallee,Biochem. 14, 3439 (1975).CrossRefGoogle Scholar
  36. 36.
    K. H. Falchuk, D. W. Fawcett, and B. L. Vallee,J. Cell Sci. 17, 57 (1975).PubMedGoogle Scholar
  37. 37.
    B. L. Vallee, inCancer Enzymology, Vol. 14, J. Schultz and F. Ahmad, ed., Academic Press, New York, 1976, p. 159.Google Scholar
  38. 38.
    P. G. W. Plagemann,J. Cell Physiol. 77, 213 (1971).PubMedCrossRefGoogle Scholar
  39. 39.
    E. P. Anderson, in The Enzymes, 3rd Ed., P. D. Boyer, ed., Vol. IX, Academic Press, New York, 1973, pp. 69–93.Google Scholar
  40. 40.
    D. H. Petering, J. Koch, S. Wielgus, and C. F. Shaw,Fed. Proc. 37, 1352 (1978).Google Scholar
  41. 41.
    H. Ohtake, K. Hasagawa, and M. Koga,Biochem. J. 174, 999 (1978).PubMedGoogle Scholar
  42. 42.
    C. D. King and J. L. Van Lancker,Arch. Biochem. Biophys. 129, 603 (1969).PubMedCrossRefGoogle Scholar
  43. 43.
    F. Maley and G. F. Maley,J. Biol. Chem. 235, 2968 (1960).PubMedGoogle Scholar
  44. 44.
    F. S. Bollum and V. R. Potter,Cancer Res. 19, 561 (1959).PubMedGoogle Scholar
  45. 45.
    H. L. Elford, M. Freese, E. Passamani, and H. P. Morris,J. Biol. Chem. 245, 5228 (1970).PubMedGoogle Scholar
  46. 46.
    F. Maley and F. G. Maley,Cancer Res. 21, 1421 (1961).PubMedGoogle Scholar
  47. 47.
    G. P. Wheeler, J. A. Alexander, D. D. Hill, and H. P. Morris,Cancer Res. 26, 2470 (1966).PubMedGoogle Scholar

Copyright information

© The Humana Press Inc 1979

Authors and Affiliations

  • David H. Petering
    • 1
  • Leon A. Saryan
    • 1
  1. 1.Department of ChemistryUniversity of Wisconsin-MilwaukeeMilwaukee

Personalised recommendations