Cell Biology and Toxicology

, Volume 10, Issue 2, pp 127–135 | Cite as

Protective effect of magnesium on DNA strand breaks induced by nickel or cadmium

  • N. A. Littlefield
  • B. S. Hass
  • S. J. James
  • L. A. Poirier


Magnesium, an essential metal that is important in the normal functioning of DNA, has been shown to interact with some of the toxic heavy metals in respect to biochemical and molecular mechanisms and in altering the tumorigenic process. This study examined the influence of magnesium in combination with nickel and cadmium in respect to damage of the DNA molecule. The purpose of this study was to evaluate the influence of magnesium on the amelioration of the toxic metals nickel and cadmium in respect to sustaining DNA damage. Two types of lymphocytes were used, i.e., primary Fischer 344 rat splenocytes and AHH-1 TK+/-, a human B-lymphoblastoid cell line that has been spontaneously transformed. These cells were grown in either a magnesium-free or magnesium-supplemented RPMI 1640 medium that was specifically formulated for this study. A 2x2 factorial design was employed with magnesium and either nickel or cadmium serving as the two factors. The experimental groups were as follows: +Mg+Ni, +Mg−Ni, −Mg+Ni, −Mg−Ni, with cadmium alternating for the nickel in the subsequent studies. The nickel or cadmium was added at a concentration of 50 μmol/L. The presence of double-stranded DNA was determined in each of the respective treatment groups with the two types of cell lines. Based on the results of this study, nickel is not directly toxic to DNA, whereas cadmium produces damage directly on the DNA molecule. The magnesium has little or no direct influence on the occurrence of DNA damage from nickel since the toxicity of nickel appears to be manifested in areas other than the DNA molecule, such as in the heterochromatin. The presence of cadmium in the treatment group resulted in DNA damage, which in turn was reduced significantly by the presence of magnesium.


cadmium DNA damage lymphocytes magnesium nickel 


ds DNA

double-stranded DNA




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  1. Aidoo A, Lyn-Cook L, Heflich RH, George EO, Casiano D. The effect of time after treatment, treatment schedule and animal age on the frequency of 6-thioguanine-resistant T-lymphocytes induced in Fischer 344 rats byN-ethyl-N-nitrosourea. Mutat Res. 1993;298:169–78.Google Scholar
  2. Aleksandrowicz J, Skotnicki, AB. Leukemia ecology. Washington D.C.: National Library of Medicine; 1982.Google Scholar
  3. Battifora HE, McCreary PA, Hahneman BM, Laing GH, Hass GM. Chronic magnesium deficiency in the rat. Arch Pathol. 1968;86:610–20.Google Scholar
  4. Bell LT, Branstrator M, Roux C, Hurley LS. Chromosomal abnormalities in maternal and fetal tissues of magnesium- or zinc-deficient rats. Teratology. 1975;12:221–6.Google Scholar
  5. Birnboim HC, Jevcak JJ. Fluorometric method for rapid detection of DNA strand breaks in human white blood cells produced by low doses of radiation. Cancer Res. 1981;41:1889–92.Google Scholar
  6. Bois P. Tumour of the thymus in magnesium-deficient rats. Nature. 1964;204:1316.Google Scholar
  7. Conway K, Costa M. The involvement of heterochromatic damage in nickel-induced transformation. Biol Trace Elem Res. 1989;21:437–44.Google Scholar
  8. Conway K, Wang X, Xu L, Costa M. Effect of magnesium on nickel-induced genotoxicity and cell transformation. Carcinogenesis. 1987;8:1115–21.Google Scholar
  9. Costa M. Perspectives of the mechanism of nickel carcinogenesis gained from models ofin vitro carcinogenesis. Environ Health Perspect. 1989;81:73–6.Google Scholar
  10. Durlach J, Bara M, Guiet-Bara M, Collery P. Relationship between magnesium, cancer and carcinogenic or anticancer metals. Anticancer Res. 1986;6:1353–62.Google Scholar
  11. Durlach J, Bara M, Guiet-Bara A. Magnesium and its relationship to oncology. Metal Ions Biol Syst. 1990;26:549–78.Google Scholar
  12. Freedman HJ, Gurtoo HL, Minowada J, Paigen B, Vaught JB. Aryl hydrocarbon hydroxylase in a stable human B-lymphocyte cell line, RPMI-1788, cultured in the absence of mitogens. Cancer Res. 1979;39:4605–11.Google Scholar
  13. Hass GM, Galt RM, Laing GH, Coogan PS. Induction of a rat T cell lymphoma-leukemia by magnesium deficiency. A study of fetal defense against maternal neoplasia. Magnesium. 1989;8:45–55.Google Scholar
  14. Jacobson KB, Turner JE. The interaction of cadmium and certain other metal ions with proteins and nucleic acids. Toxicology. 1980;16:1–37.Google Scholar
  15. James SJ, Yin L. Diet-induced DNA damage and altered nucleotide metabolism in lymphocytes from methyl-donor-deficient rats. Carcinogenesis. 1989;10:1209–14.Google Scholar
  16. Kasprzak KS, Poirier LA. 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. 1985;6:1819–21.Google Scholar
  17. Kasprazk KS, Waalkes MP. The role of calcium, magnesium and zinc in carcinogenesis. In: Poirier LA, Newberne PM, Periza MW, eds. Essential nutrients in carcinogenesis. New York: Plenum Press; 1986.Google Scholar
  18. Kasprzak KS, Quander RV, Poirier LA. Effects of calcium and magnesium salts on nickel subsulfide carcinogenicity in Fischer rats. Carcinogenesis. 1985;6:1161–6.Google Scholar
  19. Kasprzak KS, Waalkes MP, Poirier LA. Antagonism by essential metals and amino acids of nickel(II)-DNA bindingin vitro. Toxicol Appl Pharmacol. 1986;82:336–43.Google Scholar
  20. Kasprzak KS, Waalkes MP, Poirier LA. Effects of essential divalent metals on carcinogenicity and metabolism of nickel and cadmium. Biol Trace Elem Res. 1987;13:253–73.Google Scholar
  21. Nordberg GF, Anderson O. Metal interactions in carcinogenesis: enhancement, inhibition. Environ Health Perspect. 1981;40:65–81.Google Scholar
  22. Okazaki T, Mochizuki T, Tashma M, Sawada H, Uchino H. Magnesium deprivation inhibits the expression of differentiation-related phenotypes in human promyelocytic leukemia HL-60 cells. J Cell Physiol. 1987;31:50–7.Google Scholar
  23. Patierno SR, Costa M. DNA-protein cross-links induced by nickel compounds in intact cultured mammalian cells. Chem-Biol Interact. 1985;5:75–91.Google Scholar
  24. Patierno SR, Sugiyama M, Basilion JP, Costa M. Preferential DNA-protein cross-linking by NiCl2 in magnesium-insoluble regions of fractionated Chinese hamster ovary cell chromatin. Cancer Res. 1985;5:5787–94.Google Scholar
  25. Poirier LA, Kasprzak KS, Hoover KL, Wenk ML. Effects of calcium and magnesium acetates on the carcinogenicity of cadmium chloride in Wistar rats. Cancer Res. 1983;43:4575–81.Google Scholar
  26. Poirier LA, Theiss JC, Arnold LJ, Shimkin MB. Inhibition by magnesium and calcium acetates of lead subacetate- and nickel acetate-induced lung tumors in strain A mice. Cancer Res. 1984;44:1520–2.Google Scholar
  27. Rubin H. Central role for magnesium in coordinate control of metabolism and growth in animal cells. Proc Natl Acad Sci USA. 1975;72:3551–5.Google Scholar
  28. Rubin H. Effect of magnesium content on density-dependent regulation of the onset of DNA synthesis in transformed 3T3 cells. Cancer Res. 1982;42:1761–6.Google Scholar
  29. Rubin H, Vidair C, Sanui H. Restoration of normal appearance, growth behavior, and calcium content to transformed 3T3 cells by magnesium deprivation. Proc Natl Acad Sci USA. 1981;78:2350–4.Google Scholar
  30. Sen P, Conway K, Costa M. Comparison of the localization of chromosome damage induced by calcium chromate and nickel compounds. Cancer Res. 1987;47:2142–7.Google Scholar
  31. Waalkes MP, Poirier LA.In vitro cadmium-DNA interactions: cooperativity of cadmium binding and competitive antagonism by calcium, magnesium, and zinc. Toxicol Appl Pharmacol. 1984;75:539–46.Google Scholar

Copyright information

© Kluwer Academic Publishers 1994

Authors and Affiliations

  • N. A. Littlefield
    • 1
  • B. S. Hass
    • 1
  • S. J. James
    • 1
  • L. A. Poirier
    • 1
  1. 1.U.S. Public Health Service, Food and Drug Administration, National Center for Toxicological Research, Division of Nutritional ToxicologyDepartment of Health and Human ServicesJeffersonUSA

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