Abstract
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.
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References
L. Foulds,Neoplastic Development, Vol. 1, Academic Press, New York, 1969.
D. E. Poswillo and B. Cohen,Nature 231, 447 (1971).
J. R. Duncan and I. E. Dreosti,J. Natl. Cancer Inst. 55, 195 (1975).
L. Y. Y. Fong, A. Sivak, and P. M. Newberne,J. Natl. Cancer Inst. 61, 145 (1978).
P. J. Fraker, S. M. Haas, and R. W. Luecke,J. Nutr. 107, 1889 (1977).
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.
T. Tanako, G. Fernandes, C. Tsao, K. Pih, and R. A. Good,Fed. Proc. 37, 931 (1978).
M. B. Sporn, N. M. Dunlop, D. L. Newton, and J. M. Smith,Fed. Proc. 35, 1332 (1976).
J. C. Smith, Jr., E. G. McDaniel, F. F. Fau, and J. A. Halsted,Science 181, 954 (1973).
H. G. Petering, H. H. Buskirk, and J. A. Crim,Cancer Res. 27, 1115 (1967).
W. DeWys, W. J. Pories, M. C. Richter, and W. H. Stain,Proc. Soc. Expl. Biol. Med. 135, 17 (1970).
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).
W. DeWys and W. Pories,J. Natl. Cancer Inst. 48, 375 (1972).
D. H. Barr and J. W. Harris,Proc. Soc. Expl. Biol. Med. 144, 284 (1973).
D. Minkel, P. T. Dolhun, B. L. Calhoun, L. A. Saryan, and D. H. Petering,Cancer Res. in press (1979).
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).
H. H. Sandstead and R. A. Rinaldi,J. Cell Physiol. 73, 81 (1969).
H. Swenerton, R. Shrader, and L. S. Hurley,Science 166, 1014 (1969).
J. M. Hsu and W. L. Anthony,Clin. Chem. 21, 544 (1975).
A. S. Prasad and D. Oberleas,J. Lab. Clin. Med. 83, 634 (1974).
I. E. Dreosti and L. S. Hurley,Proc. Soc. Expl. Biol. Med. 150, 161 (1975).
J. R. Duncan and I. E. Dreosti,South African Med. J.,50, 711 (1976).
I. Lieberman, R. Abrahms, N. Hunt, and P. Ove,J. Biol. Chem. 238, 3955 (1963).
M. Fujioka and I. Lieberman,J. Biol. Chem. 239, 1164 (1964).
J. K. Chesters,Biochem. J. 130, 133 (1972).
J. K. Chesters,Biochem. J. 150, 211 (1975).
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.
R. O. Williams and L. A. Loeb,J. Cell. Biol. 58, 594 (1973).
K. H. Falchuk and A. Krishan,Cancer Res. 37, 2050 (1977).
L. G. Sillen and A. E. Martell,Stability Constants of Metal Ion Complexes, The Chemical Society, Burlington House, London, 1964.
E. Robbino and T. Pederson,Proc. Natl. Acad. Sci. U.S.A. 66, 1244 (1970).
J. A. Fernandez-Pol,Biochem. Biophys. Res. Commun. 78, 136 (1977).
V. D’Aurora, A. M. Stern, and D. S. Sigman,Biochem. Biophys. Res. Commun. 80, 1025 (1978).
D. H. Petering, inInorganic and Nutritional Aspects of Cancer, G. N. Schrauzer, ed., Plenum, New York, 1977, pp. 179–191.
K. H. Falchuk, A. Krishan, and B. L. Vallee,Biochem. 14, 3439 (1975).
K. H. Falchuk, D. W. Fawcett, and B. L. Vallee,J. Cell Sci. 17, 57 (1975).
B. L. Vallee, inCancer Enzymology, Vol. 14, J. Schultz and F. Ahmad, ed., Academic Press, New York, 1976, p. 159.
P. G. W. Plagemann,J. Cell Physiol. 77, 213 (1971).
E. P. Anderson, in The Enzymes, 3rd Ed., P. D. Boyer, ed., Vol. IX, Academic Press, New York, 1973, pp. 69–93.
D. H. Petering, J. Koch, S. Wielgus, and C. F. Shaw,Fed. Proc. 37, 1352 (1978).
H. Ohtake, K. Hasagawa, and M. Koga,Biochem. J. 174, 999 (1978).
C. D. King and J. L. Van Lancker,Arch. Biochem. Biophys. 129, 603 (1969).
F. Maley and G. F. Maley,J. Biol. Chem. 235, 2968 (1960).
F. S. Bollum and V. R. Potter,Cancer Res. 19, 561 (1959).
H. L. Elford, M. Freese, E. Passamani, and H. P. Morris,J. Biol. Chem. 245, 5228 (1970).
F. Maley and F. G. Maley,Cancer Res. 21, 1421 (1961).
G. P. Wheeler, J. A. Alexander, D. D. Hill, and H. P. Morris,Cancer Res. 26, 2470 (1966).
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Petering, D.H., Saryan, L.A. Control of Ehrlich cell division by zinc. Biol Trace Elem Res 1, 87–100 (1979). https://doi.org/10.1007/BF02821705
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DOI: https://doi.org/10.1007/BF02821705