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Protective effect of magnesium on DNA strand breaks induced by nickel or cadmium
Authors:N A Littlefield  B S Hass  S J James  L A Poirier
Institution:(1) U.S. Public Health Service, Food and Drug Administration, National Center for Toxicological Research, Division of Nutritional Toxicology, Department of Health and Human Services, 72079 Jefferson, AR, USA
Abstract: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 mgrmol/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.Abbreviations ds DNA double-stranded DNA - i.p. intraperitoneally
Keywords:cadmium  DNA damage  lymphocytes  magnesium  nickel
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