Abstract
Nickel compounds are recognized to cause nasal and lung cancers. Magnesium is an effective protector against nickel-induced carcinogenesis in vivo, although its mechanisms of protection remain elusive. The effects of magnesium carbonate on the cytotoxicity and genotoxicity induced by nickel subsulfide were examined with respect to the inhibition of cell proliferation, micronuclei formation, DNA-protein cross-link formation, and intranuclear nickel concentration. The generation of reactive oxygen by nickel chloride was also analyzed by observing 8-hydroxy-deoxyguanosine formation from deoxyguanosine in the presence and absence of magnesium chloride. The suppression of up to 64% of the proliferation of BALB/3T3 fibroblasts by nickel subsulfide (1 microgram/ml) was reversed by magnesium. The nickel compound increased not only the number of micronuclei but also the amount of DNA-protein cross-links examined with CHO and BALB/3T3 cells, respectively. These genotoxic effects of nickel were again lessened by magnesium carbonate. In addition, the cellular accumulation of nickel increased 80-fold with nickel subsulfide treatment and decreased with magnesium carbonate treatment. Nickel also enhanced 8-hydroxy-deoxyguanosine formation in the presence of H2O2 and ascorbic acid, where magnesium played another suppressive role. In fact, inhibition by magnesium was still observed even in the absence of nickel treatment. These results suggest that the protective role of magnesium in nickel-induced cytotoxicity and genotoxicity can be attributed to its ability to reduce either the intracellular nickel concentration or reactive oxygen formation.
Full text
PDF




Images in this article
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Athar M., Hasan S. K., Srivastava R. C. Evidence for the involvement of hydroxyl radicals in nickel mediated enhancement of lipid peroxidation: implications for nickel carcinogenesis. Biochem Biophys Res Commun. 1987 Sep 30;147(3):1276–1281. doi: 10.1016/s0006-291x(87)80208-5. [DOI] [PubMed] [Google Scholar]
- Ciccarelli R. B., Wetterhahn K. E. Nickel distribution and DNA lesions induced in rat tissues by the carcinogen nickel carbonate. Cancer Res. 1982 Sep;42(9):3544–3549. [PubMed] [Google Scholar]
- Costa M. Analysis of DNA-protein complexes induced by chemical carcinogens. J Cell Biochem. 1990 Nov;44(3):127–135. doi: 10.1002/jcb.240440302. [DOI] [PubMed] [Google Scholar]
- Costa M., Mollenhauer H. H. Carcinogenic activity of particulate nickel compounds is proportional to their cellular uptake. Science. 1980 Jul 25;209(4455):515–517. doi: 10.1126/science.7394519. [DOI] [PubMed] [Google Scholar]
- Costa M., Simmons-Hansen J., Bedrossian C. W., Bonura J., Caprioli R. M. Phagocytosis, cellular distribution, and carcinogenic activity of particulate nickel compounds in tissue culture. Cancer Res. 1981 Jul;41(7):2868–2876. [PubMed] [Google Scholar]
- Costa M., Zhuang Z., Huang X., Cosentino S., Klein C. B., Salnikow K. Molecular mechanisms of nickel carcinogenesis. Sci Total Environ. 1994 Jun 6;148(2-3):191–199. doi: 10.1016/0048-9697(94)90396-4. [DOI] [PubMed] [Google Scholar]
- Damjanov I., Sunderman F. W., Jr, Mitchell J. M., Allpass P. R. Induction of testicular sarcomas in Fischer rats by intratesticular injection of nickel subsulfide. Cancer Res. 1978 Feb;38(2):268–276. [PubMed] [Google Scholar]
- Dickens B. F., Weglicki W. B., Li Y. S., Mak I. T. Magnesium deficiency in vitro enhances free radical-induced intracellular oxidation and cytotoxicity in endothelial cells. FEBS Lett. 1992 Oct 26;311(3):187–191. doi: 10.1016/0014-5793(92)81098-7. [DOI] [PubMed] [Google Scholar]
- Fenech M., Morley A. A. Measurement of micronuclei in lymphocytes. Mutat Res. 1985 Feb-Apr;147(1-2):29–36. doi: 10.1016/0165-1161(85)90015-9. [DOI] [PubMed] [Google Scholar]
- Grandjean P., Andersen O., Nielsen G. D. Carcinogenicity of occupational nickel exposures: an evaluation of the epidemiological evidence. Am J Ind Med. 1988;13(2):193–209. doi: 10.1002/ajim.4700130202. [DOI] [PubMed] [Google Scholar]
- Hartwig A., Mullenders L. H., Schlepegrell R., Kasten U., Beyersmann D. Nickel(II) interferes with the incision step in nucleotide excision repair in mammalian cells. Cancer Res. 1994 Aug 1;54(15):4045–4051. [PubMed] [Google Scholar]
- Kasai H., Nishimura S. Hydroxylation of deoxyguanosine at the C-8 position by ascorbic acid and other reducing agents. Nucleic Acids Res. 1984 Feb 24;12(4):2137–2145. doi: 10.1093/nar/12.4.2137. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kasprzak K. S., Gabryel P., Jarczewska K. Carcinogenicity of nickel(II)hydroxides and nickel(II)sulfate in Wistar rats and its relation to the in vitro dissolution rates. Carcinogenesis. 1983;4(3):275–279. doi: 10.1093/carcin/4.3.275. [DOI] [PubMed] [Google Scholar]
- Kasprzak K. S., Hernandez L. Enhancement of hydroxylation and deglycosylation of 2'-deoxyguanosine by carcinogenic nickel compounds. Cancer Res. 1989 Nov 1;49(21):5964–5968. [PubMed] [Google Scholar]
- Kasprzak K. S., Quander R. V., Poirier L. A. Effects of calcium and magnesium salts on nickel subsulfide carcinogenicity in Fischer rats. Carcinogenesis. 1985 Aug;6(8):1161–1166. doi: 10.1093/carcin/6.8.1161. [DOI] [PubMed] [Google Scholar]
- Kasprzak K. S. The role of oxidative damage in metal carcinogenicity. Chem Res Toxicol. 1991 Nov-Dec;4(6):604–615. doi: 10.1021/tx00024a002. [DOI] [PubMed] [Google Scholar]
- Klein C. B., Frenkel K., Costa M. The role of oxidative processes in metal carcinogenesis. Chem Res Toxicol. 1991 Nov-Dec;4(6):592–604. doi: 10.1021/tx00024a001. [DOI] [PubMed] [Google Scholar]
- Krishna G., Kropko M. L., Theiss J. C. Use of the cytokinesis-block method for the analysis of micronuclei in V79 Chinese hamster lung cells: results with mitomycin C and cyclophosphamide. Mutat Res. 1989 Jan;222(1):63–69. doi: 10.1016/0165-1218(89)90036-0. [DOI] [PubMed] [Google Scholar]
- Kuchino Y., Mori F., Kasai H., Inoue H., Iwai S., Miura K., Ohtsuka E., Nishimura S. Misreading of DNA templates containing 8-hydroxydeoxyguanosine at the modified base and at adjacent residues. Nature. 1987 May 7;327(6117):77–79. doi: 10.1038/327077a0. [DOI] [PubMed] [Google Scholar]
- Lee J. E., Ciccarelli R. B., Jennette K. W. Solubilization of the carcinogen nickel subsulfide and its interaction with deoxyribonucleic acid and protein. Biochemistry. 1982 Feb 16;21(4):771–778. doi: 10.1021/bi00533a030. [DOI] [PubMed] [Google Scholar]
- Lynn S., Yew F. H., Hwang J. W., Tseng M. J., Jan K. Y. Glutathione can rescue the inhibitory effects of nickel on DNA ligation and repair synthesis. Carcinogenesis. 1994 Dec;15(12):2811–2816. doi: 10.1093/carcin/15.12.2811. [DOI] [PubMed] [Google Scholar]
- Miller C. A., 3rd, Costa M. Immunodetection of DNA-protein crosslinks by slot blotting. Mutat Res. 1990 Apr;234(2):97–106. doi: 10.1016/0165-1161(90)90036-n. [DOI] [PubMed] [Google Scholar]
- Nishimura M., Umeda M. Inducation of chromosomal aberrations in cultured mammalian cells by nickel compounds. Mutat Res. 1979 Dec;68(4):337–349. doi: 10.1016/0165-1218(79)90166-6. [DOI] [PubMed] [Google Scholar]
- Patierno S. R., Costa M. Effects of nickel(II) on nuclear protein binding to DNA in intact mammalian cells. Cancer Biochem Biophys. 1987 May;9(2):113–126. [PubMed] [Google Scholar]
- Patierno S. R., Sugiyama M., Basilion J. P., Costa M. Preferential DNA-protein cross-linking by NiCl2 in magnesium-insoluble regions of fractionated Chinese hamster ovary cell chromatin. Cancer Res. 1985 Nov;45(11 Pt 2):5787–5794. [PubMed] [Google Scholar]
- Poirier L. A., Theiss J. C., Arnold L. J., Shimkin M. B. Inhibition by magnesium and calcium acetates of lead subacetate- and nickel acetate-induced lung tumors in strain A mice. Cancer Res. 1984 Apr;44(4):1520–1522. [PubMed] [Google Scholar]
- Sen P., Conway K., Costa M. Comparison of the localization of chromosome damage induced by calcium chromate and nickel compounds. Cancer Res. 1987 Apr 15;47(8):2142–2147. [PubMed] [Google Scholar]
- Sen P., Costa M. Induction of chromosomal damage in Chinese hamster ovary cells by soluble and particulate nickel compounds: preferential fragmentation of the heterochromatic long arm of the X-chromosome by carcinogenic crystalline NiS particles. Cancer Res. 1985 May;45(5):2320–2325. [PubMed] [Google Scholar]
- Stafford R. E., Mak I. T., Kramer J. H., Weglicki W. B. Protein oxidation in magnesium deficient rat brains and kidneys. Biochem Biophys Res Commun. 1993 Oct 29;196(2):596–600. doi: 10.1006/bbrc.1993.2291. [DOI] [PubMed] [Google Scholar]
- Sugiyama M., Patierno S. R., Cantoni O., Costa M. Characterization of DNA lesions induced by CaCrO4 in synchronous and asynchronous cultured mammalian cells. Mol Pharmacol. 1986 Jun;29(6):606–613. [PubMed] [Google Scholar]
- Sunderman F. W., Jr Mechanisms of nickel carcinogenesis. Scand J Work Environ Health. 1989 Feb;15(1):1–12. doi: 10.5271/sjweh.1888. [DOI] [PubMed] [Google Scholar]
- Tsapakos M. J., Hampton T. H., Wetterhahn K. E. Chromium(VI)-induced DNA lesions and chromium distribution in rat kidney, liver, and lung. Cancer Res. 1983 Dec;43(12 Pt 1):5662–5667. [PubMed] [Google Scholar]
- Wakata A., Sasaki M. S. Measurement of micronuclei by cytokinesis-block method in cultured Chinese hamster cells: comparison with types and rates of chromosome aberrations. Mutat Res. 1987 Jan;190(1):51–57. doi: 10.1016/0165-7992(87)90082-0. [DOI] [PubMed] [Google Scholar]
- Waksvik H., Boysen M., Høgetveit A. C. Increased incidence of chromosomal aberrations in peripheral lymphocytes of retired nickel workers. Carcinogenesis. 1984 Nov;5(11):1525–1527. doi: 10.1093/carcin/5.11.1525. [DOI] [PubMed] [Google Scholar]
- Zhitkovich A., Costa M. A simple, sensitive assay to detect DNA-protein crosslinks in intact cells and in vivo. Carcinogenesis. 1992 Aug;13(8):1485–1489. doi: 10.1093/carcin/13.8.1485. [DOI] [PubMed] [Google Scholar]
- Zhuang Z., Huang X., Costa M. Protein oxidation and amino acid-DNA crosslinking by nickel compounds in intact cultured cells. Toxicol Appl Pharmacol. 1994 Jun;126(2):319–325. doi: 10.1006/taap.1994.1122. [DOI] [PubMed] [Google Scholar]


