Advertisement

The Role of Calcium, Magnesium, and Zinc in Carcinogenesis

  • Kazimierz S. Kasprzak
  • Michael P. Waalkes

Abstract

The effects of calcium, magnesium, and zinc supplementation and of magnesium depletion on carcinogenesis are comprehensively reviewed, including epidemiologic and experimental investigations. Some data on the effects of neoplasia on the homeostasis of these metals are also presented. Despite many conflicting results, this review reveals that (1) calcium supplementation is more likely to enhance than inhibit chemical carcinogenesis; (2) magnesium or zinc supplementation tends to inhibit carcinogenesis; (3) magnesium deficiency increases the incidence of neoplasia in humans and animals; (4) parenteral administration of magnesium along with a carcinogen produces local anticarcinogenic effects, while zinc’s activity tends to be systemic; and (5) there is a simple correlation between the inhibition of carcinogenesis by the magnesium and zinc supplementation and the reduction of carcinogen binding to cells and DNA. The mechanisms of these effects are not clear. They may involve molecular interactions between metal and carcinogen at different enzymatic and regulatory sites of target cells undergoing neoplastic transformation, as well as stimulation of the host immune system.

Keywords

Zinc Acetate Zinc Supplementation Syrian Hamster Zinc Chloride Dietary Zinc 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Abbreviations

DMBA

9,10-dimethylbenz[a]anthracene

DAB

4-dimethyl-aminoazobenzene

BP

benzo[a]pyrene

3-MC

3-methylcholanthrene

3′-MeDAB

3′-methyl-4-dimethylaminoazobenzene

TPA

12-O-tetra-decanoylphorbol-13-acetate (phorbol-12-myristate-13-acetate).

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    R. H. Kretsinger and D. J. Nelson, Calcium in biological systems, Coord. Chem. Rev. 18:29 (1976).CrossRefGoogle Scholar
  2. 2.
    R. B. Mikkelsen, Calcium and neoplasia, Prog. Exp. Tumor Res. 22:123 (1978).Google Scholar
  3. 3.
    L. J. Anghileri and A. M. Tuffet-Anghileri, “The Role of Calcium in Biological Systems, vol. I-III,” CRC Press, Boca Raton, Fla. (1982).Google Scholar
  4. 4.
    L. J. Anghileri, Calcium and cancer, in: “The Role of Calcium in Biological Systems, vol. III,” L. J. Anghileri and A. M. Tuffet-Anghileri, eds., CRC Press, Boca Raton, Fla. (1982).Google Scholar
  5. 5.
    M. Jagerstad, Calcium and cancer, in: “The Role of Calcium in Biological Systems, vol. III,” L. J. Anghileri and A. M. Tuffet-Anghileri, eds., CRC Press, Boca Raton, Fla. (1982).Google Scholar
  6. 6.
    M. S. Seelig, Magnesium (and trace substance) deficiencies in the pathogenesis of cancer, Biol. Trace Element Res. 1:273 (1979).CrossRefGoogle Scholar
  7. 7.
    H. J. Issaq, The role of metals in tumor development and inhibition, in: “Metal Ions in Biological Systems,” H. Siegel, ed., Marcel Dekker, New York (1980).Google Scholar
  8. 8.
    J. K. Aikawa, “Magnesium: Its Biological Significance,” CRC Press, Boca Raton, Fla. (1981).Google Scholar
  9. 9.
    F. Gaudin-Harding, Magnesium et Systeme immunitaire: Donnees recentes, Magnesium-Bull. 1a:229 (1981) (in French).Google Scholar
  10. 10.
    B. Fischer and U. Fischer, Magnesium in der Inneren Medizin, Pathophysiologie und Klinik, Magnesium-Bull. 1a:249 (1981) (in German).Google Scholar
  11. 11.
    G. F. Nordberg and O. Andersen, Metal interactions in carcinogenesis: Enhancement, inhibition, Environ. Health Perspect. 40:65 (1981).CrossRefGoogle Scholar
  12. 12.
    A. S. Prasad, “Zinc in Human Nutrition,” CRC Press, Boca Raton, Fla. (1979).Google Scholar
  13. 13.
    R. S. Beach, M. E. Gershwin, and L. S. Hurley, Zinc, copper, and manganese in immune function and experimental oncogenesis, Nutr. Cancer 3:173 (1982).Google Scholar
  14. 14.
    G. N. Schrauzer, “Inorganic and Nutritional Aspects of Cancer,” Plenum Press, New York (1978).Google Scholar
  15. 15.
    G. R. Newell and N. M. Ellison, “Progress in Cancer Research and Therapy, vol. 17. Nutrition and Cancer: Etiology and Treatment,” Raven Press, New York (1982).Google Scholar
  16. 16.
    C. McGaughey and J. L. Jensen, Promotion of benign hyperplastic lesions by calcium, magnesium and cAMP, and inhibition of tumor progression by magnesium in hamster cheek pouch, Res. Commun. Chem. Pathol. Pharmacol. 38:133 (1982).Google Scholar
  17. 17.
    L. A. Poirier, J. C. Theiss, L. J. Arnold, et al., Inhibition by magnesium and calcium acetates of lead subacetate and nickel acetate-induced lung tumors in strain A mice, Cancer Res. 44:1520 (1984).Google Scholar
  18. 18.
    L. A. Poirier, K. S. Kasprzak, K. L. Hoover, et al., Effects of calcium and magnesium acetates on the carcinogenicity of cadmium chloride in Wistar rats, Cancer Res. 43:4575 (1983).Google Scholar
  19. 19.
    K. S. Kasprzak, R. V. Quander, and L. A. Poirier, Effects of calcium and magnesium salts on nickel subsulfide carcinogenicity in Fischer rats, Carcinogenesis 6:1161 (1985).CrossRefGoogle Scholar
  20. 20.
    K. S. Kasprzak, K. L. Hoover, and L. A. Poirier, Effects of dietary calcium acetate on lead subacetate carcinogenicity in kidneys of Sprague-Dawley rats, Carcinogenesis 6:279 (1985).CrossRefGoogle Scholar
  21. 21.
    M. J. Wargovich, V. W. Eng, H. L. Newmark, et al., Calcium ameliorates the toxic effect of deoxycholic acid in colonic epithelium, Carcinogenesis 4:1205 (1983).CrossRefGoogle Scholar
  22. 22.
    M. J. Wargovich, V. W. Eng, H. L. Newmark, Calcium inhibits the damaging and compensatory proliferative effects of fatty acids on mouse colon epithelium, Cancer Lett. 23:253 (1984).CrossRefGoogle Scholar
  23. 23.
    H. L. Newmark, M. J. Wargovich, and W. R. Bruce, Colon cancer and dietary fat, phosphate, and calcium: A hypothesis, J. Natl. Cancer Inst. 72:1323 (1984).Google Scholar
  24. 24.
    K. S. Kasprzak and L. A. Poirier, Effects of calcium, magnesium and sodium acetates on tissue distribution of nickel(II) in strain A mice, In: “Chemical Toxicology and Clinical Chemistry of Metals,” S. S. Brown and J. Savory, eds., Academic Press, New York (1983).Google Scholar
  25. 25.
    K. S. Kasprzak and L. A. Poirier, Effects of calcium(II) and magnesium(II) on nickel(II) uptake and stimulation of thymidine incorporation into DNA in the lungs of strain A mice, Carcinogenesis 6:1819 (1985).CrossRefGoogle Scholar
  26. 26.
    K. S. Kasprzak and L. A. Poirier, Effects of calcium and magnesium acetates on tissue distribution of carcinogenic doses of cadmium in Wistar rats, Toxicology 34:221 (1985).CrossRefGoogle Scholar
  27. 27.
    H. D. Heath, R. E. Weiler, and G. R. Mundy, Canine lymphosarcoma: A model for study of the hypercalcemia of cancer, Calcif. Tissue Int. 30:127 (1980).CrossRefGoogle Scholar
  28. 28.
    E. Heidbreder, K. Schafferhaus, and A. Heidland, Hypercalcemia in malignant disease, Klin. Wochenschr. 61:773 (1983).CrossRefGoogle Scholar
  29. 29.
    G. R. Mundy, R. Wilkinson, and D. A. Heath, Comparative study of available medical therapy for hypercalcemia of malignancy, Am. J. Med. 74:421 (1983).CrossRefGoogle Scholar
  30. 30.
    L. J. Anghileri, Warburg’s cancer theory revisited: A fundamentally new approach, Arch. Geschwulstforsch. 53:1 (1983).Google Scholar
  31. 31.
    L. J. Anghileri, M. Heidbreder, G. Weiler, et al., Liver tumors induced by 4-dimethylaminoazobenzene: Experimental basis for a chemical carcinogenesis concept, Arch. Geschwulstforsch. 46:639 (1976).Google Scholar
  32. 32.
    L. J. Anghileri and M. Heidbreder, Cell membrane ionic permeability and mitochondria changes during 4-dimethylaminoazobenzene carcinogenesis, Arch. Geschwulstforsch. 46:389 (1976).Google Scholar
  33. 33.
    M. L. Veigl, W. D. Sedwick, and T. C. Vanaman, Calmodulin and Ca2+ in normal and transformed cells, Fed. Proc. 41:2283 (1982).Google Scholar
  34. 34.
    J. P. MacManus, Calcium-binding proteins and cell proliferation, in: “Ions, Cell Proliferation and Cancer,” A. L. Boynton, W. L. McKeehan, and J. F. Whitfield, eds., Academic Press, New York (1982).Google Scholar
  35. 35.
    J. W. Wei, H. P. Morris, and R. A. Hickie, Positive correlation between calmodulin content and hepatoma growth rates, Cancer Res. 42:2571 (1982).Google Scholar
  36. 36.
    W. Y. Cheung, Calmodulin: Its potential role in cell proliferation and heavy metal toxicity, Fed. Proc. 43:2995 (1984).Google Scholar
  37. 37.
    L. F. Jaffe, Eggs are activated by a calcium explosion: Carcinogenesis may involve calcium adaptation and habituation, In: “Ions, Cell Proliferation and Cancer,” A. L. Boynton, W. L. McKeehan, and J. F. Whitfield, eds., Academic Press, New York (1982).Google Scholar
  38. 38.
    J. P. O’Neill, R. Machanoff, J. R. San Sebastian, et al., Cytotoxicity and mutagenicity of dimethylnitrosamine in mammalian cells (CHO/HGPRT system) enhancement by calcium phosphate, Environ. Mutagen. 4:7 (1982).CrossRefGoogle Scholar
  39. 39.
    J. D. Heck and M. Costa, Extracellular requirements for the endocytosis of carcinogenic crystalline nickel sulfide particles by facultative phagocytes, Toxicol. Lett. 12:243 (1982).CrossRefGoogle Scholar
  40. 40.
    T. R. Green, D. E. Wu, and M. K. Wirtz, The oxygen-generating oxidoreductase of human neutrophils: Evidence of an obligatory requirement for calcium and magnesium for expression of catalytic activity, Biochem. Biophys. Res. Commun. 110:973 (1983).CrossRefGoogle Scholar
  41. 41.
    J. M. Robinson, J. A. Badwey, M. L. Karnovsky, et al., Superoxide release by neutrophils, synergistic effects of a phorbol ester and calcium ionophore, Biochem. Biophys. Res. Commun. 122:734 (1984).CrossRefGoogle Scholar
  42. 42.
    K. Yamanishi, H. Nishino, and A. Iwashima, Possible role of calmodulin in stimulation of hexose transport by 12-O-tetradecanoylphorbol-13-acetate, a tumor promoter, Experientia 39:1036 (1983).CrossRefGoogle Scholar
  43. 43.
    R. Levenson, D. Housman, and L. Cautley, Amiloride inhibits murine erythroleukemia cell differentiation: Evidence for a Ca2+ requirement for commitment, Proc. Natl. Acad. Sci. U.S.A. 77:5948 (1980).CrossRefGoogle Scholar
  44. 44.
    B. N. Ames, Dietary carcinogens and anticarcinogens. Oxygen radicals and degenerative diseases, Science 221:1256 (1983).CrossRefGoogle Scholar
  45. 45.
    Y. Nishizuka, The role of protein kinase C in cell surface signal transduction and tumor promotion, Nature 308:693 (1984).CrossRefGoogle Scholar
  46. 46.
    H. Hennings, D. Michael, C. Cheng, et al., Calcium regulation of growth and differentiation of mouse epidermal cells in culture, Cell 19:245 (1980).CrossRefGoogle Scholar
  47. 47.
    P. B. Fisher and I. B. Weinstein, Enhancement of cell proliferation in low calcium medium by tumor promoters, Carcinogenesis 2:89 (1981).CrossRefGoogle Scholar
  48. 48.
    C. H. Evans and A. L. Boynton, Calcium dependence of chemical carcinogen induced morphological transformation of Syrian hamster embryo cells, Cancer Lett. 15:271 (1982).CrossRefGoogle Scholar
  49. 49.
    S. H. Yuspa, M. Kulesz-Martin, T. Ben, et al., Transformation of epidermal cells in culture, J. Invest. Dermatol. 81:162s (1983).CrossRefGoogle Scholar
  50. 50.
    J. W. Grisham, J. D. Smith, and M. S. Tsao, Colony forming ability in calcium-poor medium in vitro and tumorigenicity in vivo is not coupled in clones of transformed rat hepatic epithelial cells, Cancer Res. 44:2831 (1984).Google Scholar
  51. 51.
    P. Delbet, “Politique Preventive du Cancer,” Denoel, Paris (1944) (in French).Google Scholar
  52. 52.
    A. V. Chaklin, Geographical differences in the distribution of malignant tumors. Trends in research on the etiology of human tumors, Bull. W.H.O. 27:337 (1962).Google Scholar
  53. 53.
    J. M. Blondell, The anticarcinogenic effect of magnesium, Med. Hypotheses 6:863 (1980).CrossRefGoogle Scholar
  54. 54.
    J. Aleksandrowicz and A. B. Skotnicki, “Leukemia Ecology,” National Library of Medicine, Washington, D.C. (1982).Google Scholar
  55. 55.
    R. W. Armstrong, Is there a particular kind of soil or geologic environment that predisposes to cancer? Ann. N.Y. Acad. Sci. 199:239 (1972).CrossRefGoogle Scholar
  56. 56.
    P. Collery, L. J. Anghileri, P. Coudoux, et al., Magnesium et cancer: Donnees cliniques, Magnesium-Bull. 1:11 (1981) (in French).Google Scholar
  57. 57.
    J. J. Vitale and L. S. Gottlieb, Alcohol and alcohol-related deficiencies as carcinogens, Cancer Res. 35:3336 (1975).Google Scholar
  58. 58.
    E. R. Brown, J. J. Hazdra, and O. H. Callaghan, Intracellular magnesium concentrations found in normal and leukemic human leukocytes, Proc. Am. Assoc. Cancer Res. 19:172 (1978).Google Scholar
  59. 59.
    K. B. Raja, P. M. Leach, G. P. Smith, et al., The concentration and subcellular localization of zinc, magnesium, and calcium in human polymorphonuclear leukocytes, Clin. Chim. Acta 123:19 (1982).CrossRefGoogle Scholar
  60. 60.
    J. Aleksandrowicz, J. Blicharski, J. Dzigowska, et al., Studies on the effects of magnesium salts (Delbiase) on the course of leukemia, Pol. Tyg. Lek. 25:163 (1970).Google Scholar
  61. 61.
    P. Bois, Tumors of thymus in magnesium deficient rats, Nature 204: 1316 (1964).CrossRefGoogle Scholar
  62. 62.
    P. Bois, Peripheral vasodilatation and thymic tumors in magnesium deficient rats, in: “Endocrine Aspects of Disease Processes,” G. Jasmin, ed., W. H. Green, St. Louis, Mo. (1968).Google Scholar
  63. 63.
    G. Jasmin, Action of hormones on the progression of magnesium deficiency syndrome in rats, in: “Endocrine Aspects of Disease Processes,” G. Jasmin, ed., W. H. Green, St. Louis, Mo. (1968).Google Scholar
  64. 64.
    H. A. Battifora, P. A. McCreary, B. M. Hahnemann, et al., Chronic magnesium deficiency in the rat, Arch. Pathol. 86:610 (1968).Google Scholar
  65. 65.
    G. M. Hass, G. H. Laing, R. M. Galt, et al., Role of magnesium deficiency in immunity to neoplasia in the rat, Magnesium-Bull. 1:5 (1981).Google Scholar
  66. 66.
    R. M. Gait, G. H. Laing, and G. M. Hass, Loci of blockade to intrauterine transmission of maternal rat lymphoma-leukemia to fetuses, Fed. Proc. 42:787 (1983).Google Scholar
  67. 67.
    L. H. Bell, M. Brandstrator, C. Roux, et al., Chromosomal abnormalities in maternal and fetal tissues of magnesium or zinc-deficient rats, Teratology 12:221 (1975).CrossRefGoogle Scholar
  68. 68.
    G. A. Young and F. M. Parsons, The effects of dietary deficiencies of magnesium and potassium on the growth and chemistry of transplantable tumors and host tissues in the rats, Eur. J. Cancer 13:103 (1977).CrossRefGoogle Scholar
  69. 69.
    B. J. Mills, W. L. Broghamer, P. J. Higgins, et al., Inhibition of tumor growth by magnesium depletion of rats, J. Nutr. 114:739 (1984).Google Scholar
  70. 70.
    K. A. Bazikyan and A. A. Akimov, Antiblastomogenic action of magnesium, Vopr. Onkol. 61:57 (1968).Google Scholar
  71. 71.
    F. G. Stenback, A. Ferrero, and P. Shubik, Synergistic effects of diethylnitrosamine and different dusts on respiratory carcinogenesis in hamsters, Cancer Res. 33:2209 (1973).Google Scholar
  72. 72.
    F. Stenback, A. Sellakumar, and P. Shubik, Magnesium oxide as carrier dust in benzo[a]pyrene-induced lung carcinogenesis in Syrian hamsters, J. Natl. Cancer Inst. 54:861 (1975).Google Scholar
  73. 73.
    E. Maly, Carcinogenesis from the standpoint of view of molecular geometry and synergism: Relevance of oxygen and magnesium, Med. Hypotheses 11:177 (1983).CrossRefGoogle Scholar
  74. 74.
    H. B. Gamper, K. Straub, M. Calvin, et al., DNA alkylation and unwinding induced by benzo[a]-pyrene diol epoxide: Modulation by ionic strength and superhelicity, Proc. Natl. Acad. Sci. U.S.A. 77:2000 (1980).CrossRefGoogle Scholar
  75. 75.
    M. C. McLeod and J. K. Selkirk, Physical interactions of isomeric benzo[a]pyrene diol-epoxides with DNA, Carcinogenesis 3:287 (1982).CrossRefGoogle Scholar
  76. 76.
    M. P. Waalkes and L. A. Poirier, In vitro cadmium-DNA interactions: Cooperativity of cadmium binding and competitive antagonism by calcium, magnesium, and zinc, Toxicol. Appl. Pharmacol. 75:539 (1984).CrossRefGoogle Scholar
  77. 77.
    K. S. Kasprzak, M. P. Waalkes, and L. A. Poirier, Antagonism by essential divalent metals and amino acids of nickel(II)-DNA binding in vitro, Toxicol. Appl. Pharmacol. 82 (in press, 1986).Google Scholar
  78. 78.
    W. L. McKeehan, Control of normal and transformed cell proliferation by growth factor-nutrient interactions, Fed. Proc. 43:113 (1984).Google Scholar
  79. 79.
    B. L. Vallee, Zinc biochemistry in the normal and neoplastic growth processes, in:. “Cancer Enzymology,” J. Schultz and F. Ahmad, eds., Academic Press, New York (1976).Google Scholar
  80. 80.
    W. E. C. Wacker and B. L. Vallee, Nucleic acids and metals. I. Chromium, manganese, nickel, iron and other metals in ribonucleic acid from diverse biological sources, J. Biol. Chem. 234:3257 (1959).Google Scholar
  81. 81.
    G. L. Eichhorn and Y. A. Shin, Interactions of metal ions with polynucleotides and related compounds. XII. The relative effect of various metal ions on DNA helicity, J. Am. Chem. Soc. 90:7323 (1968).CrossRefGoogle Scholar
  82. 82.
    K. Fuwa, W. E. C. Warren, R. Druyan, et al., Nucleic acids and metals. II. Transition metals as determinants of the conformation of ribonucleic acids, Proc. Natl. Acad. Sci. U.S.A. 46:1298 (1960).CrossRefGoogle Scholar
  83. 83.
    D. Barch and P. M. Iannaccone, The role of zinc deficiency in carcinogenesis, this volume.Google Scholar
  84. 84.
    P. Stocks and R. I. Davies, Zinc and copper content of soils associated with the incidence of cancer of the stomach and other organs, Br. J. Cancer 18:14 (1964).CrossRefGoogle Scholar
  85. 85.
    G. N. Schrauzer, D. A. White, and C. J. Schneider, Cancer mortality correlation studies. IV. Association with dietary intakes and blood levels of certain trace elements, notably Se-antagonists, Bioinorg. Chem. 7:35 (1977).CrossRefGoogle Scholar
  86. 86.
    R. Philipp, A. O. Hughes, and M. C. Robertson, Stomach cancer and soil metal content, Br. J. Cancer 45:482 (1982).CrossRefGoogle Scholar
  87. 87.
    I. Michalowsky, Die experimentelle Erzeugung einer teratoiden Neubildung der Hoden beim Hahn, Centralbl. allg. Path. path. Anat. 38:585 (1926) (in German).Google Scholar
  88. 88.
    L. I. Falin and K. E. Gromzewa, Experimental teratoma testis in fowl produced by injections of zinc sulfate solution, Am. J. Cancer 36:233 (1939).Google Scholar
  89. 89.
    L. I. Falin and K. E. Gromzewa, Zur Pathogenese der Geschlechtsdrusen: Teratoide Geschwulste der Geschlechtsdrusen bei Hahnen, erzeugt durch Injektionen von Zn(NO3)2-Losung, Virchows Arch. [Pathol. Anat.] 306:578 (1940) (in German).CrossRefGoogle Scholar
  90. 90.
    J. Guthrie, Observations of the zinc induced testicular teratomas of fowl, Br. J. Cancer 18:130 (1964).CrossRefGoogle Scholar
  91. 91.
    J. Guthrie, Zinc induction of testicular teratomas in Japanese quail (Coturnix coturnix japonica) after photoperiodic stimulation of the testes, Br. J. Cancer 25:311 (1971).CrossRefGoogle Scholar
  92. 92.
    V. Anissimova, Experimental zinc teratomas of the testes and their transplantation, Am. J. Cancer 36:229 (1939).Google Scholar
  93. 93.
    M. R. Riviere, I. Chouroulinkov, and M. Guerin, Production de tumeurs par injections intratesticulaires de chlorure de zinc chez le rat, Bull. Assoc. Franc. Etude Cancer 47:55 (1960) (in French).Google Scholar
  94. 94.
    J. Guthrie and O. A. Guthrie, Embryonal carcinomas in Syrian hamsters after intratesticular inoculation of zinc chloride during seasonal testicular growth, Cancer Res. 34:2612 (1974).Google Scholar
  95. 95.
    H. J. Bagg, Experimental production of teratoma testis in fowl, Am. J. Cancer 26:69 (1936).Google Scholar
  96. 96.
    L. I. Falin and W. W. Anissimowa, Zur Pathogenese der experimentellen Teratoiden Geschwulste der Geschlechtsdrusen. Teratoide Hodengeschwulst beim Hahn, erzeugt durch Emfuhrung von CuSO4, Z. Krebsforsch. 50:339 (1940) (in German).CrossRefGoogle Scholar
  97. 97.
    W. M. Bresler, On the dynamics of blastomogenesis in the testes, Acta Unio Int. Contra Cancrum 20:1501 (1964).Google Scholar
  98. 98.
    J. Guthrie, Histological effects of intra-testicular injections of cadmium chloride in domestic fowl, Br. J. Cancer 18:255 (1964).CrossRefGoogle Scholar
  99. 99.
    J. C. Heath, M. R. Daniel, J. T. Dingle, et al., Cadmium as a carcinogen, Nature 193:592 (1962).CrossRefGoogle Scholar
  100. 100.
    K. Wallenius, A. Mathur, and M. Abdulla, Effect of different levels of dietary zinc on development of chemically induced oral cancer in rats, Int. J. Oral Surg. 8:56 (1979).CrossRefGoogle Scholar
  101. 101.
    F.-W. Rath and H. Enke, Die Wirkung peroral applizierten Zinks auf die Induzierbarkeit experimenteller Hirntumoren der Ratte, Arch. Geshwulstforsch. 54:201 (1984) (in German).Google Scholar
  102. 102.
    D. E. Poswillo and B. Cohen, Inhibition of carcinogenesis by dietary zinc, Nature 231:337 (1971).CrossRefGoogle Scholar
  103. 103.
    M. B. Edwards, Chemical carcinogenesis in the cheek pouch of Syrian hamsters receiving supplementary zinc, Arch. Oral Biol. 21:133 (1976).CrossRefGoogle Scholar
  104. 104.
    L. Ciapparelli, D. H. Retief, and L. P. Fatti, The effect of zinc on 9,10-dimethyl-l,2-benzanthracene (DMBA) induced salivary gland tumours in the albino rat-a preliminary study, South Afr. J. Med. Sci. 37:85 (1972).Google Scholar
  105. 105.
    J. R. Duncan and I. E. Dreosti, Brief communication: Zinc intake, neoplastic DNA synthesis, and chemical carcinogenesis in rats and mice, J. Natl. Cancer Inst. 55:195 (1975).Google Scholar
  106. 106.
    R. Verma, S. Jain, H. L. Arora, et al., Protective efficacy of zinc supplementation on 20-MCA induced sarcomas: An experimental study in mice, Indian J. Cancer 19:126 (1982).Google Scholar
  107. 107.
    Y. Yamane and K. Sakai, Suppressive effects of concurrent administration of metal salts on carcinogenesis by 3’-methyl-4-(dimethylamino)azobenzene, and the effect of these metals on aminoazo dye metabolism during carcinogenesis, Gann 64:563 (1973).Google Scholar
  108. 108.
    S. A. Gunn, T. C. Gould, and W. A. D. Anderson, Effect of zinc on cancerogenesis by cadmium, Proc. Soc. Exp. Biol. Med. 115:653 (1964).Google Scholar
  109. 109.
    P. L. Goering and C. D. Klaassen, Zinc-induced tolerance to cadmium hepatotoxicity, Toxicol. Appl. Pharmacol. 74:299 (1984).CrossRefGoogle Scholar
  110. 110.
    G. S. Probst, N. F. Bousquet, and T. S. Miya, Correlation of hepatic metallothionein with acute cadmium toxicity in the mouse, Toxicol. Appl. Pharmacol. 39:61 (1977).CrossRefGoogle Scholar
  111. 111.
    M. Webb, The metallothioneins, Biochem. Soc. Trans. 3:632 (1975).Google Scholar
  112. 112.
    J. R. Duncan, I. E. Dreosti, and C. F. Albrecht, Brief communication: Zinc intake and growth of a transplanted hepatoma induced by 3’-methyl-4-dimethylaminoazobenzene in rats, J. Natl. Cancer Inst. 53:277 (1974).Google Scholar
  113. 113.
    A. D. Woster, M. L. Failla, M. W. Taylor, et al., Brief communication: Zinc suppression of initiation of sarcoma 180 growth, J. Natl. Cancer Inst. 54:1001 (1975).Google Scholar
  114. 114.
    J. L. Phillips and P. J. Sheridan, Effect of zinc administration on the growth of L1210 and BW5147 tumors in mice, J. Natl. Cancer Inst. 57:361 (1976).Google Scholar
  115. 115.
    J. T. McQuitty, W. D. DeWys, L. Monaco, et al., Inhibition of tumor growth by dietary zinc deficiency, Cancer Res. 30:1387 (1970).Google Scholar
  116. 116.
    H. Nishioka, Mutagenic activity of metal compounds in bacteria, Mutat. Res. 31:185 (1975).Google Scholar
  117. 117.
    J. A. DiPaolo and B. C. Casto, Quantitative studies of in vitro morphological transformation of Syrian hamster cells by inorganic metal salts, Cancer Res. 39:1008 (1979).Google Scholar
  118. 118.
    M. A. Sirover and L. A. Loeb, Infidelity of DNA synthesis in vitro: Screening for potential metal mutagens or carcinogens, Science 194:1434 (1976).CrossRefGoogle Scholar
  119. 119.
    M. Costa, O. Cantoni, M. deMars, et al., Toxic metals produce an S-phase specific cell cycle block, Res. Commun. Chem. Pathol. Pharmacol. 38:405 (1982).Google Scholar
  120. 120.
    R. Thomson, T. A. Kilroe-Smith, and I. Webster, The effect of asbestos-associated metal ions on the binding of benzo(a)pyrene to macromolecules in vitro, Environ. Res. 15:309 (1978).CrossRefGoogle Scholar
  121. 121.
    R. Thomson, I. Webster, and T. A. Kilroe-Smith, The metabolism of benzo(a)pyrene in rat liver microsomes: The effect of asbestos-associated metal ions and pH, Environ. Res. 7:149 (1974).CrossRefGoogle Scholar
  122. 122.
    M. P. Waalkes and L. A. Poirier, Interactions of cadmium with interstitial tissue of the rat testes: Uptake of cadmium by isolated interstitial cells, Biochem. Pharmacol. 34:2513 (1985).CrossRefGoogle Scholar
  123. 123.
    C. J. Pfeiffer and C.-H. Cho, Inhibition by zinc of hepatic lysosomal release of β-glucuronidase induced by phorbol-12-myristate-13-acetate (PMA), Cancer Lett. 10:51 (1980).CrossRefGoogle Scholar
  124. 124.
    J. F. Whitfield, The roles of calcium and magnesium in cell proliferation: An overview, in: “Cell Proliferation and Cancer,” A. L. Boynton, W. L. McKeehan, and J. F. Whitfield, eds., Academic Press, New York (1982).Google Scholar
  125. 125.
    A. L. Boynton, W. L. McKeehan, and J. F. Whitfield, “Ions, Cell Proliferation and Cancer,” Academic Press, New York (1982).Google Scholar
  126. 126.
    N. J. Shear, The role of sodium, potassium, calcium and magnesium in cancer: A review, Am. J. Cancer 18:924 (1933).Google Scholar

Copyright information

© Plenum Press, New York 1986

Authors and Affiliations

  • Kazimierz S. Kasprzak
    • 1
  • Michael P. Waalkes
    • 1
  1. 1.Nutrition and Metabolism Section, Laboratory of Comparative Carcinogenesis, Division of Cancer EtiologyNational Cancer InstituteFrederickUSA

Personalised recommendations