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Cadmium and Its Impact on Genomic Stability

  • Andrea HartwigEmail author
Chapter

Abstract

The carcinogenicity of cadmium for humans and experimental animals has been long established, most evident for tumors in the lung and kidney, but with increasing evidence also for other tumor locations. While cadmium does not interact directly with DNA, elevated levels of reactive oxygen species (ROS), the interference with the cellular response to DNA damage including all major DNA repair systems as well as the inactivation of tumor suppressor functions appear to be of major importance, thereby increasing the susceptibility towards exogenous and endogenous DNA damage. Furthermore, the deregulation of cell growth, the resistance to apoptosis, as well as epigenetic alterations have been demonstrated in diverse experimental systems. Particularly sensitive targets appear to be proteins with zinc-binding structures, present in many DNA repair proteins, transcription factors and in the tumor suppressor protein p53. The interaction with critical thiol groups and/or the enhanced generation of ROS may also provoke an interference with cellular redox regulation of critical signaling pathways. Especially the combination of these multiple mechanisms may give rise to a high degree of genomic instability in cadmium-adapted cells, relevant not only for tumor initiation but also for later steps in tumor development.

References

  1. 1.
    Hartwig A (2013) Cadmium and cancer. Met Ions Life Sci 11:491–507PubMedCrossRefPubMedCentralGoogle Scholar
  2. 2.
    IARC (1993) Beryllium, Cadmium, Mercury and exposures in the glass manufacturing industry, vol 58. Monographs for the evaluation of the carcinogenic risk to humansGoogle Scholar
  3. 3.
    IARC (1997) Supplement: Cadmium and Cadmium compounds. Monographs for the evaluation of the carcinogenic risk to humansGoogle Scholar
  4. 4.
    IARC (2012) Arsenic, metals fibres and dusts. IARC monographs 100C:121–145Google Scholar
  5. 5.
    Greim H (2006) Cadmium and its inorganic compounds. MAK Value Documentation 2006. The MAK Collection for Occupational Health and Safety 1–41Google Scholar
  6. 6.
    Stayner L, Smith R, Schnorr T, Lemen R, Thun M (1993) Lung cancer. Ann Epidemiol 3(1):114–116PubMedCrossRefGoogle Scholar
  7. 7.
    Sorahan T, Esmen NA (2004) Lung cancer mortality in UK nickel-cadmium battery workers, 1947–2000. Occup Environ Med 61(2):108–116PubMedPubMedCentralCrossRefGoogle Scholar
  8. 8.
    Sorahan T (2009) Lung cancer mortality in arsenic-exposed workers from a cadmium recovery plant. Occup Med (Lond) 59(4):264–266CrossRefGoogle Scholar
  9. 9.
    Jarup L, Bellander T, Hogstedt C, Spang G (1998) Mortality and cancer incidence in Swedish battery workers exposed to cadmium and nickel. Occup Environ Med 55(11):755–759PubMedPubMedCentralCrossRefGoogle Scholar
  10. 10.
    Nawrot T, Plusquin M, Hogervorst J, Roels HA, Celis H, Thijs L, Vangronsveld J, Van Hecke E, Staessen JA (2006) Environmental exposure to cadmium and risk of cancer: a prospective population-based study. Lancet Oncol 7(2):119–126PubMedCrossRefGoogle Scholar
  11. 11.
    Pesch B, Haerting J, Ranft U, Klimpel A, Oelschlägel B, Schill W (2000) Occupational risk factors for renal cell carcinoma: agent-specific results from a case-control study in Germany. MURC Study Group. Multicenter urothelial and renal cancer study. Int J Epidemiol 29 (6):1014–1024PubMedCrossRefGoogle Scholar
  12. 12.
    Hu J, Mao Y, White K (2002) Renal cell carcinoma and occupational exposure to chemicals in Canada. Occup Med (Lond) 52(3):157–164CrossRefGoogle Scholar
  13. 13.
    Siemiatycki J (1991) Risk Factors for Cancer in the Workplace. CRC Press, Boca Raton, FloridaGoogle Scholar
  14. 14.
    Kellen E, Zeegers MP, Hond ED, Buntinx F (2007) Blood cadmium may be associated with bladder carcinogenesis: the Belgian case-control study on bladder cancer. Cancer Detec Prev 31:77–82PubMedCrossRefGoogle Scholar
  15. 15.
    McElroy JA, Shafer MM, Trentham-Dietz A, Hampton JM, Newcomb PA (2006) Cadmium exposure and breast cancer risk. J Natl Cancer Inst 98(12):869–873PubMedCrossRefGoogle Scholar
  16. 16.
    Akesson A, Julin B, Wolk A (2008) Long-term dietary cadmium intake and postmenopausal endometrial cancer incidence: a population-based prospective cohort study. Cancer Res 68(15):6435–6441PubMedCrossRefGoogle Scholar
  17. 17.
    Heinrich U, Peters L, Ernst H, Rittinghausen S, Dasenbrock C, König H (1989) Investigation on the carcinogenic effects of various cadmium compounds after inhalation exposure in hamsters and mice. Exp Pathol 37(1–4):253–258PubMedCrossRefGoogle Scholar
  18. 18.
    Takenaka S, Oldiges H, Konig H, Hochrainer D, Oberdörster G (1983) Carcinogenicity of cadmium chloride aerosols in Wistar rats. J Natl Cancer Inst 70(2):367–373PubMedGoogle Scholar
  19. 19.
    Glaser U, Hochrainer D, Otto FJ, Oldiges H (1990) Carcinogenicity and toxicity of four cadmium compounds inhaled by rats. Toxicol Environ Chem 27:153–162CrossRefGoogle Scholar
  20. 20.
    Huff J, Lunn RM, Waalkes MP, Tomatis L, Infante PF (2007) Cadmium-induced cancers in animals and in humans. Int J Occup Environ Health 13(2):202–212PubMedPubMedCentralCrossRefGoogle Scholar
  21. 21.
    Valverde M, Trejo C, Rojas E (2001) Is the capacity of lead acetate and cadmium chloride to induce genotoxic damage due to direct DNA-metal interaction? Mutagenesis 16(3):265–270PubMedCrossRefGoogle Scholar
  22. 22.
    Beyersmann D, Hartwig A (2008) Carcinogenic metal compounds: recent insight into molecular and cellular mechanisms. Arch Toxicol 82(8):493–512PubMedCrossRefGoogle Scholar
  23. 23.
    Filipic M (2012) Mechanisms of cadmium induced genomic instability. Mutat Res 733(1–2):69–77PubMedCrossRefGoogle Scholar
  24. 24.
    Waisberg M, Joseph P, Hale B, Beyersmann D (2003) Molecular and cellular mechanisms of cadmium carcinogenesis. Toxicology 192(2–3):95–117PubMedCrossRefGoogle Scholar
  25. 25.
    Filipic M, Hei TK (2004) Mutagenicity of cadmium in mammalian cells: implication of oxidative DNA damage. Mutat Res 546(1–2):81–91PubMedCrossRefGoogle Scholar
  26. 26.
    Tapisso JT, Marques CC, Mathias Mda L, Ramalhinho Mda G (2009) Induction of micronuclei and sister chromatid exchange in bone-marrow cells and abnormalities in sperm of Algerian mice (Mus spretus) exposed to cadmium, lead and zinc. Mutat Res 678(1):59–64PubMedCrossRefGoogle Scholar
  27. 27.
    Nersesyan A, Kundi M, Waldherr M, Setayesh T, Misik M, Wultsch G, Filipic M, Mazzaron Barcelos GR, Knasmueller S (2016) Results of micronucleus assays with individuals who are occupationally and environmentally exposed to mercury, lead and cadmium. Mutat Res 770(Pt A):119–139PubMedCrossRefGoogle Scholar
  28. 28.
    Valko M, Jomova K, Rhodes CJ, Kuca K, Musilek K (2016) Redox- and non-redox-metal-induced formation of free radicals and their role in human disease. Arch Toxicol 90(1):1–37PubMedCrossRefGoogle Scholar
  29. 29.
    Valko M, Rhodes CJ, Moncol J, Izakovic M, Mazur M (2006) Free radicals, metals and antioxidants in oxidative stress-induced cancer. Chem Biol Interact 160(1):1–40PubMedCrossRefGoogle Scholar
  30. 30.
    Cadet J, Douki T, Ravanat JL (2010) Oxidatively generated base damage to cellular DNA. Free Radic Biol Med 49(1):9–21PubMedCrossRefPubMedCentralGoogle Scholar
  31. 31.
    Kryston TB, Georgiev AB, Pissis P, Georgakilas AG (2011) Role of oxidative stress and DNA damage in human carcinogenesis. Mutat Res 711(1–2):193–201PubMedCrossRefPubMedCentralGoogle Scholar
  32. 32.
    Liu J, Qu W, Kadiiska MB (2009) Role of oxidative stress in cadmium toxicity and carcinogenesis. Toxicol Appl Pharmacol 238(3):209–214PubMedPubMedCentralCrossRefGoogle Scholar
  33. 33.
    Dally H, Hartwig A (1997) Induction and repair inhibition of oxidative DNA damage by nickel(II) and cadmium(II) in mammalian cells. Carcinogenesis 18(5):1021–1026PubMedCrossRefPubMedCentralGoogle Scholar
  34. 34.
    Schwerdtle T, Ebert F, Thuy C, Richter C, Mullenders LH, Hartwig A (2010) Genotoxicity of soluble and particulate cadmium compounds: impact on oxidative DNA damage and nucleotide excision repair. Chem Res Toxicol 23(2):432–442PubMedCrossRefPubMedCentralGoogle Scholar
  35. 35.
    Ochi T, Ohsawa M (1985) Participation of active oxygen species in the induction of chromosomal aberrations by cadmium chloride in cultured Chinese hamster cells. Mutat Res 143(3):137–142PubMedCrossRefPubMedCentralGoogle Scholar
  36. 36.
    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(2):77–88PubMedCrossRefPubMedCentralGoogle Scholar
  37. 37.
    Valko M, Rhodes CJ, Moncol J, Izakovic M, Mazur M (2006) Free radicals, metals and antioxidants in oxidative stress-induced cancer. Chem Biol Interact 160(1):1–40PubMedCrossRefGoogle Scholar
  38. 38.
    Fischer BM, Neumann D, Piberger AL, Risnes SF, Koberle B, Hartwig A (2016) Use of high-throughput RT-qPCR to assess modulations of gene expression profiles related to genomic stability and interactions by cadmium. Arch Toxicol 90(11):2745–2761PubMedCrossRefPubMedCentralGoogle Scholar
  39. 39.
    O’Brien P, Salacinski HJ (1998) Evidence that the reactions of cadmium in the presence of metallothionein can produce hydroxyl radicals. Arch Toxicol 72:690–700PubMedCrossRefPubMedCentralGoogle Scholar
  40. 40.
    Wang Y, Fang J, Leonard SS, Krishna Rao KM (2004) Cadmium inhibits the electron transfer chain and induces Reactive Oxygen Species. Free Radical Biol Med 36:1434–1443CrossRefGoogle Scholar
  41. 41.
    Genestra M (2007) Oxyl radicals, redox-sensitive signalling cascades and antioxidants. Cell Signal 19(9):1807–1819PubMedCrossRefPubMedCentralGoogle Scholar
  42. 42.
    Hartwig A (2013) Metal interaction with redox regulation: an integrating concept in metal carcinogenesis? Free Radic Biol Med 55:63–72PubMedCrossRefPubMedCentralGoogle Scholar
  43. 43.
    Hakem R (2008) DNA-damage repair; the good, the bad, and the ugly. EMBO J 27(4):589–605PubMedPubMedCentralCrossRefGoogle Scholar
  44. 44.
    Camenisch U, Naegeli H (2009) Role of DNA repair in the protection against genotoxic stress. EXS 99:111–150PubMedPubMedCentralGoogle Scholar
  45. 45.
    Christmann M, Tomicic MT, Roos WP, Kaina B (2003) Mechanisms of human DNA repair: an update. Toxicology 193(1–2):3–34PubMedCrossRefPubMedCentralGoogle Scholar
  46. 46.
    Fousteri M, Mullenders LH (2008) Transcription-coupled nucleotide excision repair in mammalian cells: molecular mechanisms and biological effects. Cell Res 18(1):73–84PubMedCrossRefPubMedCentralGoogle Scholar
  47. 47.
    Hartwig A (1994) Role of DNA repair inhibition in lead- and cadmium-induced genotoxicity: a review. Environ Health Perspect 102(Suppl 3):45–50PubMedPubMedCentralCrossRefGoogle Scholar
  48. 48.
    Giaginis C, Gatzidou E, Theocharis S (2006) DNA repair systems as targets of cadmium toxicity. Toxicol Appl Pharmacol 213(3):282–290PubMedCrossRefPubMedCentralGoogle Scholar
  49. 49.
    Hartwig A (2010) Mechanisms in cadmium-induced carcinogenicity: recent insights. Biometals 23(5):951–960PubMedCrossRefPubMedCentralGoogle Scholar
  50. 50.
    Koedrith P, Seo YR (2011) Advances in carcinogenic metal toxicity and potential molecular markers. Int J Mol Sci 12(12):9576–9595PubMedPubMedCentralCrossRefGoogle Scholar
  51. 51.
    de Boer J, Hoeijmakers JH (2000) Nucleotide excision repair and human syndromes. Carcinogenesis 21(3):453–460PubMedCrossRefPubMedCentralGoogle Scholar
  52. 52.
    Hartmann A, Speit G (1996) Effect of arsenic and cadmium on the persistence of mutagen-induced DNA lesions in human cells. Environ Mol Mutagen 27(2):98–104PubMedCrossRefPubMedCentralGoogle Scholar
  53. 53.
    Snyder RD, Davis GF, Lachmann PJ (1989) Inhibition by metals of X-ray and ultraviolet-induced DNA repair in human cells. Biol Trace Elem Res 21:389–398PubMedCrossRefPubMedCentralGoogle Scholar
  54. 54.
    Mackay JP, Crossley M (1998) Zinc fingers are sticking together. Trends Biochem Sci 23(1):1–4PubMedCrossRefPubMedCentralGoogle Scholar
  55. 55.
    Hartwig A (2001) Zinc finger proteins as potential targets for toxic metal ions: differential effects on structure and function. Antioxid Redox Signal 3(4):625–634PubMedCrossRefPubMedCentralGoogle Scholar
  56. 56.
    Witkiewicz-Kucharczyk A, Bal W (2006) Damage of zinc fingers in DNA repair proteins, a novel molecular mechanism in carcinogenesis. Toxicol Lett 162(1):29–42PubMedCrossRefPubMedCentralGoogle Scholar
  57. 57.
    Asmuss M, Mullenders LH, Hartwig A (2000) Interference by toxic metal compounds with isolated zinc finger DNA repair proteins. Toxicol Lett 112–113:227–231PubMedCrossRefPubMedCentralGoogle Scholar
  58. 58.
    Hartmann M, Hartwig A (1998) Disturbance of DNA damage recognition after UV-irradiation by nickel(II) and cadmium(II) in mammalian cells. Carcinogenesis 19(4):617–621PubMedCrossRefPubMedCentralGoogle Scholar
  59. 59.
    Buchko GW, Hess NJ, Kennedy MA (2000) Cadmium mutagenicity and human nucleotide excision repair protein XPA: CD, EXAFS and (1)H/(15)N-NMR spectroscopic studies on the zinc(II)- and cadmium(II)-associated minimal DNA-binding domain (M98-F219). Carcinogenesis 21(5):1051–1057PubMedCrossRefPubMedCentralGoogle Scholar
  60. 60.
    Kopera E, Schwerdtle T, Hartwig A, Bal W (2004) Co(II) and Cd(II) substitute for Zn(II) in the zinc finger derived from the DNA repair protein XPA, demonstrating a variety of potential mechanisms of toxicity. Chem Res Toxicol 17(11):1452–1458PubMedCrossRefPubMedCentralGoogle Scholar
  61. 61.
    Asmuss M, Mullenders LH, Eker A, Hartwig A (2000) Differential effects of toxic metal compounds on the activities of Fpg and XPA, two zinc finger proteins involved in DNA repair. Carcinogenesis 21(11):2097–2104PubMedCrossRefPubMedCentralGoogle Scholar
  62. 62.
    Fatur T, Lah TT, Filipic M (2003) Cadmium inhibits repair of UV-, methyl methanesulfonate- and N-methyl-N-nitrosourea-induced DNA damage in Chinese hamster ovary cells. Mutat Res 529(1–2):109–116PubMedCrossRefPubMedCentralGoogle Scholar
  63. 63.
    Bialkowski K, Kasprzak KS (1998) A novel assay of 8-oxo-2’-deoxyguanosine 5’-triphosphate pyrophosphohydrolase (8-oxo-dGTPase) activity in cultured cells and its use for evaluation of cadmium(II) inhibition of this activity. Nucleic Acids Res 26(13):3194–3201PubMedPubMedCentralCrossRefGoogle Scholar
  64. 64.
    Zharkov DO, Rosenquist TA (2002) Inactivation of mammalian 8-oxoguanine-DNA glycosylase by cadmium(II): implications for cadmium genotoxicity. DNA Repair (Amst) 1(8):661–670CrossRefGoogle Scholar
  65. 65.
    Potts RJ, Watkin RD, Hart BA (2003) Cadmium exposure down-regulates 8-oxoguanine DNA glycosylase expression in rat lung and alveolar epithelial cells. Toxicology 184(2–3):189–202PubMedCrossRefPubMedCentralGoogle Scholar
  66. 66.
    Hamann I, König C, Richter C, Jahnke G, Hartwig A (2011) Impact of cadmium on hOGG1 and APE1 as a function of the cellular p 53 status. Mutat Res May 13 Epub ahead of printGoogle Scholar
  67. 67.
    Bravard A, Campalans A, Vacher M, Gouget B, Levalois C, Chevillard S, Radicella JP (2010) Inactivation by oxidation and recruitment into stress granules of hOGG1 but not APE1 in human cells exposed to sub-lethal concentrations of cadmium. Mutat Res 685(1–2):61–69PubMedCrossRefPubMedCentralGoogle Scholar
  68. 68.
    Youn CK, Kim SH, Lee DY, Song SH, Chang IY, Hyun JW, Chung MH, You HJ (2005) Cadmium down-regulates human OGG1 through suppression of Sp1 activity. J Biol Chem 280(26):25185–25195PubMedCrossRefPubMedCentralGoogle Scholar
  69. 69.
    Kothinti RK, Blodgett AB, Petering DH, Tabatabai NM (2010) Cadmium down-regulation of kidney Sp1 binding to mouse SGLT1 and SGLT2 gene promoters: possible reaction of cadmium with the zinc finger domain of Sp1. Toxicol Appl Pharmacol 244(3):254–262PubMedPubMedCentralCrossRefGoogle Scholar
  70. 70.
    Bialkowski K, Bialkowska A, Kasprzak KS (1999) Cadmium(II), unlike nickel(II), inhibits 8-oxo-dGTPase activity and increases 8-oxo-dG level in DNA of the rat testis, a target organ for cadmium(II) carcinogenesis. Carcinogenesis 20(8):1621–1624PubMedCrossRefPubMedCentralGoogle Scholar
  71. 71.
    Beneke S, Bürkle A (2007) Poly(ADP-ribosyl)ation in mammalian ageing. Nucleic Acids Res 35(22):7456–7465PubMedPubMedCentralCrossRefGoogle Scholar
  72. 72.
    Petrucco S (2003) Sensing DNA damage by PARP-like fingers. Nucleic Acids Res 31(23):6689–6699PubMedPubMedCentralCrossRefGoogle Scholar
  73. 73.
    Hartwig A, Asmuss M, Ehleben I, Herzer U, Kostelac D, Pelzer A, Schwerdtle T, Bürkle A (2002) Interference by toxic metal ions with DNA repair processes and cell cycle control: molecular mechanisms. Environ Health Perspect 110(Suppl 5):797–799PubMedPubMedCentralCrossRefGoogle Scholar
  74. 74.
    Hsieh P, Yamane K (2008) DNA mismatch repair: molecular mechanism, cancer, and ageing. Mech Ageing Dev 129(7–8):391–407PubMedPubMedCentralCrossRefGoogle Scholar
  75. 75.
    Kunkel TA, Erie DA (2015) Eukaryotic Mismatch Repair in Relation to DNA Replication. Annu Rev Genet 49:291–313PubMedPubMedCentralCrossRefGoogle Scholar
  76. 76.
    Modrich P (1994) Mismatch repair, genetic stability, and cancer. Science 266(5193):1959–1960PubMedCrossRefPubMedCentralGoogle Scholar
  77. 77.
    O’Brien V, Brown R (2006) Signalling cell cycle arrest and cell death through the MMR System. Carcinogenesis 27(4):682–692PubMedCrossRefPubMedCentralGoogle Scholar
  78. 78.
    Jiricny J (2006) The multifaceted mismatch-repair system. Nat Rev Mol Cell Biol 7(5):335–346PubMedCrossRefPubMedCentralGoogle Scholar
  79. 79.
    Jin YH, Clark AB, Slebos RJ, Al-Refai H, Taylor JA, Kunkel TA, Resnick MA, Gordenin DA (2003) Cadmium is a mutagen that acts by inhibiting mismatch repair. Nat Genet 34(3):326–329PubMedPubMedCentralCrossRefGoogle Scholar
  80. 80.
    Oliveira H, Lopes T, Almeida T, Pereira Mde L, Santos C (2012) Cadmium-induced genetic instability in mice testis. Hum Exp Toxicol 31(12):1228–1236PubMedCrossRefGoogle Scholar
  81. 81.
    Lutzen A, Liberti SE, Rasmussen LJ (2004) Cadmium inhibits human DNA mismatch repair in vivo. Biochem Biophys Res Commun 321(1):21–25PubMedCrossRefGoogle Scholar
  82. 82.
    Wieland M, Levin MK, Hingorani KS, Biro FN, Hingorani MM (2009) Mechanism of cadmium-mediated inhibition of Msh2-Msh6 function in DNA mismatch repair. Biochemistry 48(40):9492–9502PubMedPubMedCentralCrossRefGoogle Scholar
  83. 83.
    Wu CL, Huang LY, Chang CL (2017) Linking arsenite- and cadmium-generated oxidative stress to microsatellite instability in vitro and in vivo. Free Radic Biol Med 112:12–23PubMedCrossRefGoogle Scholar
  84. 84.
    Viau M, Gastaldo J, Bencokova Z, Joubert A, Foray N (2008) Cadmium inhibits non-homologous end-joining and over-activates the MRE11-dependent repair pathway. Mutat Res 654(1):13–21PubMedCrossRefGoogle Scholar
  85. 85.
    Li W, Gu X, Zhang X, Kong J, Ding N, Qi Y, Zhang Y, Wang J, Huang D (2015) Cadmium delays non-homologous end joining (NHEJ) repair via inhibition of DNA-PKcs phosphorylation and downregulation of XRCC4 and Ligase IV. Mutat Res 779:112–123PubMedCrossRefGoogle Scholar
  86. 86.
    Morales ME, Derbes RS, Ade CM, Ortego JC, Stark J, Deininger PL, Roy-Engel AM (2016) Heavy Metal Exposure Influences Double Strand Break DNA Repair Outcomes. PLoS ONE 11(3):e0151367PubMedPubMedCentralCrossRefGoogle Scholar
  87. 87.
    Hainaut P, Hollstein M (2000) p53 and human cancer: the first ten thousand mutations. Adv Cancer Res 77:81–137PubMedCrossRefGoogle Scholar
  88. 88.
    Cao F, Zhou T, Simpson D, Zhou Y, Boyer J, Chen B, Jin T, Cordeiro-Stone M, Kaufmann W (2007) p53-Dependent but ATM-independent inhibition of DNA synthesis and G2 arrest in cadmium-treated human fibroblasts. Toxicol Appl Pharmacol 218(2):174–185PubMedCrossRefGoogle Scholar
  89. 89.
    Chatterjee S, Kundu S, Sengupta S, Bhattacharyya A (2009) Divergence to apoptosis from ROS induced cell cycle arrest: effect of cadmium. Mutat Res 663(1–2):22–31PubMedCrossRefGoogle Scholar
  90. 90.
    Yu X, Sidhu JS, Hong S, Robinson JF, Ponce RA, Faustman EM (2011) Cadmium induced p53-dependent activation of stress signaling, accumulation of ubiquitinated proteins, and apoptosis in mouse embryonic fibroblast cells. Toxicol Sci 120(2):403–412PubMedPubMedCentralCrossRefGoogle Scholar
  91. 91.
    Meplan C, Mann K, Hainaut P (1999) Cadmium induces conformational modifications of wild-type p53 and suppresses p53 response to DNA damage in cultured cells. J Biol Chem 274(44):31663–31670PubMedCrossRefGoogle Scholar
  92. 92.
    Hart BA, Potts RJ, Watkin RD (2001) Cadmium adaptation in the lung—a double-edged sword? Toxicology 160(1–3):65–70PubMedCrossRefGoogle Scholar
  93. 93.
    Joseph P (2009) Mechanisms of cadmium carcinogenesis. Toxicol Appl Pharmacol 238(3):272–279PubMedCrossRefGoogle Scholar
  94. 94.
    Thevenod F (2009) Cadmium and cellular signaling cascades: to be or not to be? Toxicol Appl Pharmacol 238(3):221–239PubMedCrossRefGoogle Scholar
  95. 95.
    Chen L, Liu L, Huang S (2008) Cadmium activates the mitogen-activated protein kinase (MAPK) pathway via induction of reactive oxygen species and inhibition of protein phosphatases 2A and 5. Free Radic Biol Med 45(7):1035–1044PubMedCrossRefGoogle Scholar
  96. 96.
    Chen L, Liu L, Yin J, Luo Y, Huang S (2009) Hydrogen peroxide-induced neuronal apoptosis is associated with inhibition of protein phosphatase 2A and 5, leading to activation of MAPK pathway. Int J Biochem Cell Biol 41(6):1284–1295PubMedCrossRefGoogle Scholar
  97. 97.
    Kim HS, Song MC, Kwak IH, Park TJ, Lim IK (2003) Constitutive induction of p-Erk1/2 accompanied by reduced activities of protein phosphatases 1 and 2A and MKP3 due to reactive oxygen species during cellular senescence. J Biol Chem 278(39):37497–37510PubMedCrossRefGoogle Scholar
  98. 98.
    He X, Chen MG, Ma Q (2008) Activation of Nrf2 in defense against cadmium-induced oxidative stress. Chem Res Toxicol 21(7):1375–1383PubMedCrossRefGoogle Scholar
  99. 99.
    Chen J, Shaikh ZA (2009) Activation of Nrf2 by cadmium and its role in protection against cadmium-induced apoptosis in rat kidney cells. Toxicol Appl Pharmacol 241(1):81–89PubMedCrossRefGoogle Scholar
  100. 100.
    Qu W, Ke H, Pi J, Broderick D, French JE, Webber MM, Waalkes MP (2007) Acquisition of apoptotic resistance in cadmium-transformed human prostate epithelial cells: Bcl-2 overexpression blocks the activation of JNK signal transduction pathway. Environ Health Perspect 115(7):1094–1100PubMedPubMedCentralCrossRefGoogle Scholar
  101. 101.
    Wang B, Li Y, Shao C, Tan Y, Cai L (2012) Cadmium and its epigenetic effects. Curr Med Chem 19(16):2611–2620PubMedCrossRefGoogle Scholar
  102. 102.
    Suzuki M, Takeda S, Teraoka-Nishitani N, Yamagata A, Tanaka T, Sasaki M, Yasuda N, Oda M, Okano T, Yamahira K, Nakamura Y, Kobayashi T, Kino K, Miyazawa H, Waalkes MP, Takiguchi M (2017) Cadmium-induced malignant transformation of rat liver cells: Potential key role and regulatory mechanism of altered apolipoprotein E expression in enhanced invasiveness. Toxicology 382:16–23PubMedCrossRefGoogle Scholar
  103. 103.
    Thevenod F (2010) Catch me if you can! Novel aspects of cadmium transport in mammalian cells. Biometals 23(5):857–875PubMedCrossRefGoogle Scholar
  104. 104.
    Costa M, Heck JD, Robison SH (1982) Selective phagocytosis of crystalline metal sulfide particles and DNA strand breaks as a mechanism for the induction of cellular transformation. Cancer Res 42(7):2757–2763PubMedGoogle Scholar
  105. 105.
    Evans RM, Davies PJ, Costa M (1982) Video time-lapse microscopy of phagocytosis and intracellular fate of crystalline nickel sulfide particles in cultured mammalian cells. Cancer Res 42(7):2729–2735PubMedGoogle Scholar
  106. 106.
    Heinrich U (1992) Pulmonary carcinogenicity of cadmium by inhalation in animals. IARC Sci Publ 118:405–413Google Scholar
  107. 107.
    Martelli A, Rousselet E, Dycke C, Bouron A, Moulis JM (2006) Cadmium toxicity in animal cells by interference with essential metals. Biochimie 88(11):1807–1814PubMedCrossRefGoogle Scholar
  108. 108.
    Potts RJ, Bespalov IA, Wallace SS, Melamede RJ, Hart BA (2001) Inhibition of oxidative DNA repair in cadmium-adapted alveolar epithelial cells and the potential involvement of metallothionein. Toxicology 161(1–2):25–38PubMedCrossRefGoogle Scholar
  109. 109.
    Zhou T, Jia X, Chapin RE, Maronpot RR, Harris MW, Liu J, Waalkes MP, Eddy EM (2004) Cadmium at a non-toxic dose alters gene expression in mouse testes. Toxicol Lett 154(3):191–200PubMedCrossRefGoogle Scholar
  110. 110.
    Lichtlen P, Schaffner W (2001) Putting its fingers on stressful situations: the heavy metal-regulatory transcription factor MTF-1. BioEssays 23(11):1010–1017PubMedCrossRefPubMedCentralGoogle Scholar
  111. 111.
    Takiguchi M, Achanzar WE, Qu W, Li G, Waalkes MP (2003) Effects of cadmium on DNA-(Cytosine-5) methyltransferase activity and DNA methylation status during cadmium-induced cellular transformation. Exp Cell Res 286(2):355–365PubMedCrossRefPubMedCentralGoogle Scholar
  112. 112.
    Prozialeck WC, Lamar PC (1999) Interaction of cadmium (Cd(2 +)) with a 13-residue polypeptide analog of a putative calcium-binding motif of E-cadherin. Biochim Biophys Acta 1451(1):93–100PubMedCrossRefPubMedCentralGoogle Scholar
  113. 113.
    Prozialeck WC, Lamar PC, Lynch SM (2003) Cadmium alters the localization of N-cadherin, E-cadherin, and beta-catenin in the proximal tubule epithelium. Toxicol Appl Pharmacol 189(3):180–195PubMedCrossRefPubMedCentralGoogle Scholar
  114. 114.
    Moulis JM (2010) Cellular mechanisms of cadmium toxicity related to the homeostasis of essential metals. Biometals 23(5):877–896PubMedCrossRefPubMedCentralGoogle Scholar
  115. 115.
    Brigelius-Flohe R, Flohe L (2011) Basic principles and emerging concepts in the redox control of transcription factors. Antioxid Redox Signal 15(8):2335–2381PubMedPubMedCentralCrossRefGoogle Scholar
  116. 116.
    Giles GI (2006) The redox regulation of thiol dependent signaling pathways in cancer. Curr Pharm Des 12(34):4427–4443PubMedCrossRefPubMedCentralGoogle Scholar
  117. 117.
    Ray PD, Huang BW, Tsuji Y (2012) Reactive oxygen species (ROS) homeostasis and redox regulation in cellular signaling. Cell Signal 24(5):981–990PubMedPubMedCentralCrossRefGoogle Scholar
  118. 118.
    Byrne C, Divekar SD, Storchan GB, Parodi DA, Martin MB (2009) Cadmium—a metallohormone? Toxicol Appl Pharmacol 238(3):266–271PubMedPubMedCentralCrossRefGoogle Scholar
  119. 119.
    Klaassen CD, Liu J, Diwan BA (2009) Metallothionein protection of cadmium toxicity. Toxicol Appl Pharmacol 238(3):215–220PubMedPubMedCentralCrossRefGoogle Scholar
  120. 120.
    Singh KP, Kumari R, Pevey C, Jackson D, DuMond JW (2009) Long duration exposure to cadmium leads to increased cell survival, decreased DNA repair capacity, and genomic instability in mouse testicular Leydig cells. Cancer Lett 279(1):84–92PubMedCrossRefGoogle Scholar
  121. 121.
    Börjesson J, Bellander T, Jarup L, Elinder CG, Mattsson S (1997) In vivo analysis of cadmium in battery workers versus measurements of blood, urine, and workplace air. Occup Environ Med 54(6):424–431PubMedPubMedCentralCrossRefGoogle Scholar
  122. 122.
    Hengstler JG, Bolm-Audorff U, Faldum A, Janssen K, Reifenrath M, Gotte W, Jung D, Mayer-Popken O, Fuchs J, Gebhard S, Bienfait HG, Schlink K, Dietrich C, Faust D, Epe B, Oesch F (2003) Occupational exposure to heavy metals: DNA damage induction and DNA repair inhibition prove co-exposures to cadmium, cobalt and lead as more dangerous than hitherto expected. Carcinogenesis 24(1):63–73PubMedCrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2018

Authors and Affiliations

  1. 1.Food Chemistry and Toxicology, Karlsruhe Institute of Technology (KIT)KarlsruheGermany

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