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Metal ions and carcinogenesis

  • Chapter
Cancer: Cell Structures, Carcinogens and Genomic Instability

Part of the book series: Experientia Supplementum ((EXS,volume 96))

Abstract

Metals are essential for the normal functioning of living organisms. Their uses in biological systems are varied, but are frequently associated with sites of critical protein function, such as zinc finger motifs and electron or oxygen carriers. These functions only require essential metals in minute amounts, hence they are termed trace metals. Other metals are, however, less beneficial, owing to their ability to promote a wide variety of deleterious health effects, including cancer. Metals such as arsenic, for example, can produce a variety of diseases ranging from keratosis of the palms and feet to cancers in multiple target organs. The nature and type of metal-induced pathologies appear to be dependent on the concentration, speciation, and length of exposure. Unfortunately, human contact with metals is an inescapable consequence of human life, with exposures occurring from both occupational and environmental sources. A uniform mechanism of action for all harmful metals is unlikely, if not implausible, given the diverse chemical properties of each metal. In this chapter we will review the mechanisms of carcinogenesis of arsenic, cadmium, chromium, and nickel, the four known carcinogenic metals that are best understood. The key areas of speciation, bioavailability, and mechanisms of action are discussed with particular reference to the role of metals in alteration of gene expression and maintenance of genomic integrity.

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References

  1. IARC (1980) IARC monographs on the evaluation of carcinogenic risks to humans. Arsenic and arsenic compounds. Vol. 23, Lyon, France. The Agency; Secretariat of the World Health Organization, Geneva

    Google Scholar 

  2. IARC (1980) Some Metals and Metallic Compounds. IARC monographs on the evaluation of carcinogenic risks to humans. Vol. 23. World Health Organization, Geneva

    Google Scholar 

  3. IARC (1990) Chromium, nickel and welding. IARC monographs on the evaluation of carcinogenic risks to humans, Vol. 49, Lyon, France. World Health Organization, Geneva

    Google Scholar 

  4. IARC (1993) Beryllium, cadmium, mercury, and exposures in the glass manufacturing industry. IARC monographs on the evaluation of carcinogenic risks to humans, Vol. 58. World Health Organization, Geneva

    Google Scholar 

  5. Snow ET (1992) Metal carcinogenesis: mechanistic implications. Pharmacol Ther 53: 31–65

    Article  CAS  PubMed  Google Scholar 

  6. Klein CB, Snow ET, Frenkel K (1998) Molecular mechanisms in metal carcinogenesis: role of oxidative stress. In: OI Aruoma, B Halliwell(eds): Molecular Biology of Free Radicals in Human Diseases. OICA International, Saint Lucia, London, 80–137

    Google Scholar 

  7. Theophanides T, Anastassopoulou J (2002) Copper and carcinogenesis. Crit Rev Oncol Hematol 42: 57–64

    CAS  PubMed  Google Scholar 

  8. Huang X (2003) Iron overload and its association with cancer risk in humans: evidence for iron as a carcinogenic metal. Mutat Res 533: 153–171

    CAS  PubMed  Google Scholar 

  9. Cangul H, Broday L, Salnikow K, Sutherland J, Peng W, Zhang Q, Poltaratsky V, Yee H, Zoroddu MA, Costa M (2002) Molecular mechanisms of nickel carcinogenesis. Toxicol Lett 127: 69–75

    Article  CAS  PubMed  Google Scholar 

  10. Waisberg M, Joseph P, Hale B, Beyersmann D (2003) Molecular and cellular mechanisms of cadmium carcinogenesis. Toxicology 192: 95–117

    Article  CAS  PubMed  Google Scholar 

  11. Toyokuni S (2002) Iron and carcinogenesis: from Fenton reaction to target genes. Redox Rep 7: 189–197

    Article  CAS  PubMed  Google Scholar 

  12. Kasprzak KS, Sunderman FW Jr, Salnikow K (2003) Nickel carcinogenesis. Mutat Res 533: 67–97

    CAS  PubMed  Google Scholar 

  13. O’Brien TJ, Ceryak S, Patierno SR (2003) Complexities of chromium carcinogenesis: role of cellular response, repair and recovery mechanisms. Mutat Res 533: 3–36

    CAS  PubMed  Google Scholar 

  14. Huang C, Ke Q, Costa M, Shi X (2004) Molecular mechanisms of arsenic carcinogenesis. Mol Cell Biochem 255: 57–66

    Article  CAS  PubMed  Google Scholar 

  15. Dubins JS, LaVelle JM (1986) Nickel(II) genotoxicity: potentiation of mutagenesis of simple alkylating agents. Mutat Res 162: 187–199

    CAS  PubMed  Google Scholar 

  16. Ding M, Shi X (2002) Molecular mechanisms of Cr(VI)-induced carcinogenesis. Mol Cell Biochem 234–235: 293–300

    PubMed  Google Scholar 

  17. Galaris D, Evangelou A (2002) The role of oxidative stress in mechanisms of metal-induced carcinogenesis. Crit Rev Oncol Hematol 42: 93–103

    PubMed  Google Scholar 

  18. Kim JY, Mukherjee S, Ngo LC, Christiani DC (2004) Urinary 8-hydroxy-2’-deoxyguanosine as a biomarker of oxidative DNA damage in workers exposed to fine particulates. Environ Health Perspect 112: 666–671

    CAS  PubMed  Google Scholar 

  19. Machella N, Regoli F, Cambria A, Santella RM (2004) Application of an immunoperoxidase staining method for detection of 7,8-dihydro-8-oxodeoxyguanosine as a biomarker of chemical-induced oxidative stress in marine organisms. Aquat Toxicol 67: 23–32

    Article  CAS  PubMed  Google Scholar 

  20. De Flora S, Bagnasco M, Serra D, Zanacchi P (1990) Genotoxicity of chromium compounds. A review. Mutat Res 238: 99–172

    PubMed  Google Scholar 

  21. Lee AJ, Hodges NJ, Chipman JK (2004) Modified comet assay as a biomarker of sodium dichromate-induced oxidative DNA damage: optimization and reproducibility. Biomarkers 9: 103–115

    Article  CAS  PubMed  Google Scholar 

  22. Zhitkovich A (2005) Importance of Chromium-DNA Adducts in Mutagenicity and Toxicity of Chromium(VI). Chem Res Toxicol 18: 3–11

    Google Scholar 

  23. Klein CB, Costa M (1997) DNA methylation, heterochromatin and epigenetic carcinogens. Mutat Res 386: 163–180

    CAS  PubMed  Google Scholar 

  24. Costa M (2002) Molecular mechanisms of nickel carcinogenesis. Biol Chem 383: 961–967

    Google Scholar 

  25. Chen H, Li S, Liu J, Diwan BA, Barrett JC, Waalkes MP (2004) Chronic inorganic arsenic exposure induces hepatic global and individual gene hypomethylation: implications for arsenic hepatocarcinogenesis. Carcinogenesis 25: 1779–1786

    CAS  PubMed  Google Scholar 

  26. Lee TC, Wei ML, Chang WJ, Ho IC, Lo JF, Jan KY, Huang H (1989) Elevation of glutathione levels and glutathione S-transferase activity in arsenic-resistant Chinese hamster ovary cells. In Vitro Cell Dev Biol 25: 442–448

    CAS  PubMed  Google Scholar 

  27. Stohs SJ, Bagchi D, Hassoun E, Bagchi M (2001) Oxidative mechanisms in the toxicity of chromium and cadmium ions. J Environ Pathol Toxicol Oncol 20: 77–88

    CAS  PubMed  Google Scholar 

  28. Ercal N, Gurer-Orhan H, Aykin-Burns N (2001) Toxic metals and oxidative stress part I: mechanisms involved in metal-induced oxidative damage. Curr Top Med Chem 1: 529–539

    Article  CAS  PubMed  Google Scholar 

  29. Prozialeck WC, Grunwald GB, Dey PM, Reuhl KR, Parrish AR (2002) Cadherins and NCAM as potential targets in metal toxicity. Toxicol Appl Pharmacol 182: 255–265

    Article  CAS  PubMed  Google Scholar 

  30. Waxman S, Anderson KC (2001) History of the development of arsenic derivatives in cancer therapy. Oncologist 6,Suppl 2: 3–10

    CAS  PubMed  Google Scholar 

  31. Weider B, Fournier JH (1999) Activation analyses of authenticated hairs of Napoleon Bonaparte confirm arsenic poisoning. Am J Forensic Med Pathol 20: 378–382

    Article  CAS  PubMed  Google Scholar 

  32. Evens AM, Tallman MS, Gartenhaus RB (2004) The potential of arsenic trioxide in the treatment of malignant disease: past, present, and future. Leuk Res 28: 891–900

    Article  CAS  PubMed  Google Scholar 

  33. Agency for Toxic Substances and Disease Registry (ATSDR) (2000) Toxicological Profile for arsenic. Update. Agency for Toxic Substances and Disease Registry, Department of Health and Human Services, Public Health Service, Atlanta, GA

    Google Scholar 

  34. Alam MG, Allinson G, Stagnitti F, Tanaka A, Westbrooke M (2002) Arsenic contamination in Bangladesh groundwater: a major environmental and social disaster. Int J Environ Health Res 12: 235–253

    Article  CAS  PubMed  Google Scholar 

  35. Guha Mazumder DN (2003) Chronic arsenic toxicity: clinical features, epidemiology, and treatment: experience in West Bengal. J Environ Sci Health Part A Tox Hazard Subst Environ Eng 38: 141–163

    CAS  Google Scholar 

  36. Subramanian KS, Kosnett MJ (1998) Human exposures to arsenic from consumption of well water in West Bengal, India. Int J Occup Environ Health 4: 217–230

    CAS  PubMed  Google Scholar 

  37. Chowdhury UK, Biswas BK, Chowdhury TR, Samanta G, Mandal BK, Basu GC, Chanda CR, Lodh D, Saha KC, Mukherjee SK et al. (2000) Groundwater arsenic contamination in Bangladesh and West Bengal, India. Environ Health Perspect 108: 393–397

    CAS  PubMed  Google Scholar 

  38. Chen Y, Ahsan H (2004) Cancer burden from arsenic in drinking water in Bangladesh. Am J Public Health 94: 741–744

    PubMed  Google Scholar 

  39. Rahman MM, Mandal BK, Chowdhury TR, Sengupta MK, Chowdhury UK, Lodh D, Chanda CR, Basu GK, Mukherjee SC, Saha KC et al. (2003) Arsenic groundwater contamination and sufferings of people in North 24-Parganas, one of the nine arsenic affected districts of West bengal, India. J Environ Sci Health Part A Tox Hazard Subst Environ Eng 38: 25–59

    Google Scholar 

  40. Kligerman AD, Doerr CL, Tennant AH, Harrington-Brock K, Allen JW, Winkfield E, Poorman-Allen P, Kundu B, Funasaka K, Roop BC et al. (2003) Methylated trivalent arsenicals as candidate ultimate genotoxic forms of arsenic: induction of chromosomal mutations but not gene mutations. Environ Mol Mutagen 42: 192–205

    Article  CAS  PubMed  Google Scholar 

  41. Sahu G, Jena R (2005) Significance of intracellular arsenic trioxide for therapeutic response in acute promyelocytic leukemia. Am J Hematol 78: 113–116

    Article  CAS  PubMed  Google Scholar 

  42. Dopp E, Hartmann LM, Florea A-M, von Recklinghausen U, Pieper R, Shokouhi B, Rettenmeier AW, Hirner AV, Obe G (2004) Uptake of inorganic and organic derivatives of arsenic associated with induced cytotoxic and genotoxic effects in Chinese hamster ovary (CHO) cells. Toxicol Appl Pharmacol 201: 156–165

    Article  CAS  PubMed  Google Scholar 

  43. Komissarova EV, Saha SK, Rossman TG (2005) Dead or dying: the importance of time in cytotoxicity assays using arsenite as an example. Toxicol Appl Pharmacol 202: 99–107

    Article  CAS  PubMed  Google Scholar 

  44. Schwerdtle T, Walter I, Mackiw I, Hartwig A (2003) Induction of oxidative DNA damage by arsenite and its trivalent and pentavalent methylated metabolites in cultured human cells and isolated DNA. Carcinogenesis 24: 967–974

    Article  CAS  PubMed  Google Scholar 

  45. Le XC, Cullen WR, Reimer KJ (1994) Human Urinary Arsenic Excretion after One-Time Ingestion of Seaweed, Crab, and Shrimp. Clinical Chemistry 40: 617–624

    CAS  PubMed  Google Scholar 

  46. Andrewes P, Demarini DM, Funasaka K, Wallace K, Lai VW, Sun H, Cullen WR, Kitchin KT (2004) Do arsenosugars pose a risk to human health? The comparative toxicities of a trivalent and pentavalent arsenosugar. Environ Sci Technol 38: 4140–4148

    Article  CAS  PubMed  Google Scholar 

  47. Tchounwou PB, Patlolla AK, Centeno JA (2003) Carcinogenic and systemic health effects associated with arsenic exposure—a critical review. Toxicol Pathol 31: 575–588

    CAS  PubMed  Google Scholar 

  48. Schwartz RA (1996) Premalignant keratinocytic neoplasms. J Am Acad Dermatol 35(2 Pt 1): 223–242

    CAS  PubMed  Google Scholar 

  49. Liu Z, Shen J, Carbrey JM, Mukhopadhyay R, Agre P, Rosen BP (2002) Arsenite transport by mammalian aquaglyceroporins AQP7 and AQP9. Proc Natl Acad Sci USA 99: 6053–6058

    CAS  PubMed  Google Scholar 

  50. Chowdhury UK, Rahman MM, Sengupta MK, Lodh D, Chanda CR, Roy S, Quamruzzaman Q, Tokunaga H, Ando M, Chakraborti D (2003) Pattern of excretion of arsenic compounds [arsenite, arsenate, MMA(V), DMA(V)] in urine of children compared to adults from an arsenic exposed area in Bangladesh. J Environ Sci Health Part A Tox Hazard Subst Environ Eng 38: 87–113

    Google Scholar 

  51. Buchet JP, Lauwerys R, Roels H (1981) Comparison of the urinary excretion of arsenic metabolites after a single oral dose of sodium arsenite, monomethylarsonate, or dimethylarsinate in man. Int Arch Occup Environ Health 48: 71–79

    CAS  PubMed  Google Scholar 

  52. Hakala E, Pyy L (1995) Assessment of exposure to inorganic arsenic by determining the arsenic species excreted in urine. Toxicol Lett 77: 249–258

    Article  CAS  PubMed  Google Scholar 

  53. Yamanaka K, Hoshino M, Okamoto M, Sawamura R, Hasegawa A, Okada S (1990) Induction of DNA damage by dimethylarsine, a metabolite of inorganic arsenics, is for the major part likely due to its peroxyl radical. Biochem Biophys Res Commun 168: 58–64

    Article  CAS  PubMed  Google Scholar 

  54. McMurray CT, Tainer JA (2003) Cancer, cadmium and genome integrity. Nat Genet 34: 239–241

    Article  CAS  PubMed  Google Scholar 

  55. Peters JM, Thomas D, Falk H, Oberdorster G, Smith TJ (1986) Contribution of metals to respiratory cancer. Environ Health Perspect 70: 71–83

    CAS  PubMed  Google Scholar 

  56. Jin T, Lu J, Nordberg M (1998) Toxicokinetics and biochemistry of cadmium with special emphasis on the role of metallothionein. Neurotoxicology 19: 529–535

    CAS  PubMed  Google Scholar 

  57. Sorahan T, Lancashire RJ (1997) Lung cancer mortality in a cohort of workers employed at a cadmium recovery plant in the United States: an analysis with detailed job histories. Occup Environ Med 54: 194–201

    CAS  PubMed  Google Scholar 

  58. Stayner L, Smith R, Thun M, Schnorr T, Lemen R (1992) A quantitative assessment of lung cancer risk and occupational cadmium exposure. IARC Sci Publ 118: 447–455

    CAS  PubMed  Google Scholar 

  59. Agency for Toxic Substances and Disease Registry (ATSDR) (1999) Toxicological Profile for cadmium. Agency for Toxic Substances and Disease Registry, Department of Health and Human Services, Public Health Service, Atlanta, GA

    Google Scholar 

  60. Agency for Toxic Substances and Disease Registry (ATSDR) (2000) Toxicological Profile for chromium. Agency for Toxic Substances and Disease Registry, Department of Health and Human Services, Public Health Service, Atlanta, GA

    Google Scholar 

  61. Vincent JB (2000) The biochemistry of chromium. J Nutr 130: 715–718

    CAS  PubMed  Google Scholar 

  62. Arslan P, Beltrame M, Tomasi A (1987) Intracellular chromium reduction. Biochim Biophys Acta

    Google Scholar 

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Authors and Affiliations

  1. Centre for Cellular and Molecular Biology, School of Biological and Chemical Sciences, Deakin University, 221 Burwood Highway, Burwood, Victoria, Australia, 3125

    Troy R. Durham & Elizabeth T. Snow

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  1. Troy R. Durham
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  2. Elizabeth T. Snow
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Durham, T.R., Snow, E.T. (2006). Metal ions and carcinogenesis. In: Cancer: Cell Structures, Carcinogens and Genomic Instability. Experientia Supplementum, vol 96. Birkhäuser Basel. https://doi.org/10.1007/3-7643-7378-4_5

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