Skip to main content
SpringerLink
Log in

Molecular Mechanisms of Metal-Induced Carcinogenesis

  • Chapter
  • First Online:
Cancer Research: An Interdisciplinary Approach

Part of the book series: Interdisciplinary Cancer Research ((ICR,volume 1))

Abstract

Occupational and environmental exposures to metals are strongly associated with an increased risk of various cancers. Although carcinogenesis caused by metals has been intensively investigated, the exact mechanisms are still ambiguous. Given the different chemical properties of metals, a uniform mechanism of action for all metals is unlikely. Recent evidence suggests that carcinogenic metals induce genotoxicity in a diversity of ways, either alone or by enhancing the effects of other agents.

This review summarizes current information on the mechanisms of carcinogenesis of metals including arsenic, chromium, cadmium, nickel, cobalt, beryllium, copper, lead, vanadium, silver, zinc, selenium, iron, antimony, manganese, and aluminum. Each of these metals is distinct in its primary modes of action; yet there are several mechanisms induced by more than one metal, including the induction of oxidative stress, inhibition of DNA metabolism and repair, formation of DNA and/or protein cross-links, induction of cancer-related genes and proteins, and disturbance of cell cycle and function. Also attention is paid to responsive signal transduction pathways with major roles in cell growth and development such as growth factor receptors, ras, src, MAPKs, NFkB, Nrf2, HIF-1, p53, NFAT, and AP-1. These signaling pathways can lead to induction of transcription in genes that promote proliferation or confer apoptosis resistance to metal-exposed cells. Dysregulation of protective pathways, including cellular antioxidant network against free radicals as well as impaired DNA repair, is related to oncogenic stimulation. Epigenetic modifications including DNA methylation, histone modification, microRNAs, and their roles in metal carcinogenesis are also reviewed.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 219.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 279.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Achanzar WE, Achanzar KB, Lewis JG, Webber MM, Waalkes MP (2000) Cadmium induces c-myc, p53, and c-Jun expression in normal human prostate epithelial cells as a prelude to apoptosis. Toxicol Appl Pharmacol 164:291–300

    CAS  PubMed  Google Scholar 

  • Agudo A, Ahrens W, Benhamou E, Benhamou S, Boffetta P, Darby SC, Forastiere F, Fortes C, Gaborieau V, González CA (2000) Lung cancer and cigarette smoking in women: a multicenter case-control study in Europe. Int J Cancer 88:820–827

    CAS  PubMed  Google Scholar 

  • Aiyar J, Berkovits HJ, Floyd RA, Wetterhahn KE (1991) Reaction of chromium (VI) with glutathione or with hydrogen peroxide: identification of reactive intermediates and their role in chromium (VI)-induced DNA damage. Environ Health Perspect 92:53–62

    CAS  PubMed  PubMed Central  Google Scholar 

  • Andrew AS, Karagas MR, Hamilton JW (2003) Decreased DNA repair gene expression among individuals exposed to arsenic in United States drinking water. Int J Cancer 104:263–268

    CAS  PubMed  Google Scholar 

  • Arita A, Costa M (2009) Epigenetics in metal carcinogenesis: nickel, arsenic, chromium and cadmium. Metallomics 1:222–228

    CAS  PubMed  Google Scholar 

  • Bagchi D, Bagchi M, Stohs SJ (2001) Chromium (VI)-induced oxidative stress, apoptotic cell death and modulation of p53 tumor suppressor gene. Mol Cell Biochem 222:149–158

    CAS  PubMed  Google Scholar 

  • Baines AT, Xu D, Der CJ (2011) Inhibition of Ras for cancer treatment: the search continues. Future Med Chem 3:1787–1808

    CAS  PubMed  Google Scholar 

  • Bal W, Kasprzak KS (2002) Induction of oxidative DNA damage by carcinogenic metals. Toxicol Lett 127:55–62

    CAS  PubMed  Google Scholar 

  • Bal W, Schwerdtle T, Hartwig A (2003) Mechanism of nickel assault on the zinc finger of DNA repair protein XPA. Chem Res Toxicol 16:242–248

    CAS  PubMed  Google Scholar 

  • Basu A, Ghosh P, Das JK, Banerjee A, Ray K, Giri AK (2004) Micronuclei as biomarkers of carcinogen exposure in populations exposed to arsenic through drinking water in West Bengal, India: a comparative study in three cell types. Cancer Epidemiol Biomark Prev 13:820–827

    CAS  Google Scholar 

  • Beezhold K, Liu J, Kan H, Meighan T, Castranova V, Shi X, Chen F (2011) miR-190-mediated downregulation of PHLPP contributes to arsenic-induced Akt activation and carcinogenesis. Toxicol Sci 123:411–420

    CAS  PubMed  PubMed Central  Google Scholar 

  • Beyersmann D (2002) Effects of carcinogenic metals on gene expression. Toxicol Lett 127:63–68

    CAS  PubMed  Google Scholar 

  • Beyersmann D, Hartwig A (2008) Carcinogenic metal compounds: recent insight into molecular and cellular mechanisms. Arch Toxicol 82:493–512

    CAS  PubMed  Google Scholar 

  • Bhattacharjee P, Banerjee M, Giri AK (2013) Role of genomic instability in arsenic-induced carcinogenicity. Rev Environ Int 53:29–40

    CAS  Google Scholar 

  • Bollati V, Marinelli B, Apostoli P, Bonzini M, Nordio F, Hoxha M, Pegoraro V, Motta V, Tarantini L, Cantone L (2010) Exposure to metal-rich particulate matter modifies the expression of candidate microRNAs in peripheral blood leukocytes. Environ Health Perspect 118:763–768

    CAS  PubMed  PubMed Central  Google Scholar 

  • Boutten A, Goven D, Artaud-Macari E, Boczkowski J, Bonay M (2011) NRF2 targeting: a promising therapeutic strategy in chronic obstructive pulmonary disease. Trends Mol Med 17:363–371

    CAS  PubMed  Google Scholar 

  • Brezova V, Valko M, Breza M, Morris H, Telser J, Dvoranova D, Kaiserova K, Varecka L, Mazur M, Leibfritz D (2003) Role of radicals and singlet oxygen in photoactivated DNA cleavage by the anticancer drug camptothecin: an electron paramagnetic resonance study. J Phys Chem B 107:2415–2425

    CAS  Google Scholar 

  • Cadenas E, Davies KJ (2000) Mitochondrial free radical generation, oxidative stress, and aging. Free Radic Biol Med 29:222–230

    CAS  PubMed  Google Scholar 

  • Cadet J, Douki T, Ravanat J-L (2010) Oxidatively generated base damage to cellular DNA. Free Radic Biol Med 49:9–21

    CAS  PubMed  Google Scholar 

  • Cadet J, Douki T, Ravanat J-L (2011) Measurement of oxidatively generated base damage in cellular DNA. Mutation Res 711:3–12

    CAS  PubMed  Google Scholar 

  • Cadet J, Ravanat J-L, TavernaPorro M, Menoni H, Angelov D (2012) Oxidatively generated complex DNA damage: tandem and clustered lesions. Cancer Lett 327:5–15

    CAS  PubMed  Google Scholar 

  • Cameron KS, Buchner V, Tchounwou PB (2011) Exploring the molecular mechanisms of nickel-induced genotoxicity and carcinogenicity: a literature review. Rev Environ Health 26(2):81–92

    CAS  PubMed  PubMed Central  Google Scholar 

  • Catalani S, Apostoli P (2011) Interactions by carcinogenic metal compounds with DNA repair processes. Selected Topics in DNA Repair

    Google Scholar 

  • Chanda S, Dasgupta UB, GuhaMazumder D, Gupta M, Chaudhuri U, Lahiri S, Das S, Ghosh N, Chatterjee D (2006) DNA hypermethylation of promoter of gene p53 and p16 in arsenic-exposed people with and without malignancy. Toxicol Sci 89:431–437

    CAS  PubMed  Google Scholar 

  • Chang Q, Bhatia D, Zhang Y, Meighan T, Castranova V, Shi X, Chen F (2007) Incorporation of an internal ribosome entry site–dependent mechanism in arsenic-induced GADD45α expression. Cancer Res 67:6146–6154

    CAS  PubMed  Google Scholar 

  • Chen F, Shi X (2002) Signaling from toxic metals to NF-kappaB and beyond: not just a matter of reactive oxygen species. Environ Health Perspect 110:807–811

    CAS  PubMed  PubMed Central  Google Scholar 

  • Chen W, Li Z, Bai L, Lin Y (2011) NF-kappaB in lung cancer, a carcinogenesis mediator and a prevention and therapy target. Front Biosci Landmark 16:1172–1185

    CAS  Google Scholar 

  • Chervona Y, Costa M (2012) The control of histone methylation and gene expression by oxidative stress, hypoxia, and metals. Free Radic Biol Med 53:1041–1047

    CAS  PubMed  PubMed Central  Google Scholar 

  • Chou W-C, Hawkins AL, Barrett JF, Griffin CA, Dang CV (2001) Arsenic inhibition of telomerase transcription leads to genetic instability. J Clin Invest 108:1541–1547

    CAS  PubMed  PubMed Central  Google Scholar 

  • Christmann M, Tomicic MT, Roos WP, Kaina B (2003) Mechanisms of human DNA repair: an update. Toxicology 193:3–34

    CAS  PubMed  Google Scholar 

  • D’Assoro AB, Lingle WL, Salisbury JL (2002) Centrosome amplification and the development of cancer. Oncogene 21:6146–6153

    PubMed  Google Scholar 

  • Davis CD, Uthus EO (2004) DNA methylation, cancer susceptibility, and nutrient interactions. Exp Biol Med 229:988–995

    CAS  Google Scholar 

  • De Boeck M, Kirsch-Volders M, Lison D (2003) Cobalt and antimony: genotoxicity and carcinogenicity. Mut Res 533:135–152

    Google Scholar 

  • De Boer J, Hoeijmakers JH (2000) Nucleotide excision repair and human syndromes. Carcinogenesis 21:453–460

    PubMed  Google Scholar 

  • de Flora S (1989) Mechanism of chromium (VI) metabolism and genotoxicity. Life Chem Rep 7:169–244

    Google Scholar 

  • Denkhaus E, Salnikow K (2002) Nickel essentiality, toxicity, and carcinogenicity. Crit Rev Oncol Hematol 42:35–56

    CAS  PubMed  Google Scholar 

  • Durham TR, Snow ET (2006) Metal ions and carcinogenesis. Cancer 96:97–130

    CAS  Google Scholar 

  • El-Murr N, Abidi Z, Wanherdrick K, Svrcek M, Gaub M-P, Flejou J-F, Hamelin R, Duval A, Lesuffleur T (2012) MiRNA genes constitute new targets for microsatellite instability in colorectal cancer. PLoS One 7:e31862

    CAS  PubMed  PubMed Central  Google Scholar 

  • Ralph F (2011) Quadruplex DNA: a promising drug target for the medicinal inorganic chemist. Curr Top Med Chem 11:572–590

    CAS  PubMed  Google Scholar 

  • Faita F, Cori L, Bianchi F, Andreassi MG (2013) Arsenic-induced genotoxicity and genetic susceptibility to arsenic-related pathologies. Int J Environ Res Public Health 10:1527–1546

    CAS  PubMed  PubMed Central  Google Scholar 

  • Figgitt M, Newson R, Leslie IJ, Fisher J, Ingham E, Case CP (2010) The genotoxicity of physiological concentrations of chromium (Cr (III) and Cr (VI)) and cobalt (co (II)): an in vitro study. Mut Res 688:53–61

    CAS  Google Scholar 

  • Filipič M (2012) Mechanisms of cadmium induced genomic instability. Mut Res 733:69–77

    Google Scholar 

  • Fortini P, Pascucci B, Parlanti E, D’errico M, Simonelli V, Dogliotti E (2003) The base excision repair: mechanisms and its relevance for cancer susceptibility. Biochimie 85:1053–1071

    CAS  PubMed  Google Scholar 

  • Frame MC (2002) Src in cancer: deregulation and consequences for cell behaviour. Biochimica et Biophysica Acta (BBA)-reviews on. Cancer 1602:114–130

    CAS  Google Scholar 

  • Galanis A, Karapetsas A, Sandaltzopoulos R (2009) Metal-induced carcinogenesis, oxidative stress and hypoxia signalling. Mut Res 674:31–35

    CAS  Google Scholar 

  • 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 

  • Gantke T, Sriskantharajah S, Sadowski M, Ley SC (2012) IκB kinase regulation of the TPL-2/ERK MAPK pathway. Immunol Rev 246:168–182

    PubMed  Google Scholar 

  • Gao J, Roy S, Tong L, Argos M, Jasmine F, Rahaman R, Rakibuz-Zaman M, Parvez F, Ahmed A, Hore SK (2015) Arsenic exposure, telomere length, and expression of telomere-related genes among Bangladeshi individuals. Environ Res 136:462–469

    CAS  PubMed  Google Scholar 

  • Gao M, Binks S, Chipman J, Levy L, Braithwaite R, Brown S (1992) Induction of DNA strand breaks in peripheral lymphocytes by soluble chromium compounds. Hum Exp Toxicol 11:77–82

    CAS  PubMed  Google Scholar 

  • Gerber G, Leonard A, Hantson P (2002) Carcinogenicity, mutagenicity and teratogenicity of manganese compounds. Crit Rev Oncol Hematol 42:25–34

    CAS  PubMed  Google Scholar 

  • Harris GK, Shi X (2003) Signaling by carcinogenic metals and metal-induced reactive oxygen species. Mut Res 533:183–200

    CAS  Google Scholar 

  • Hartwig A (1998) Carcinogenicity of metal compounds: possible role of DNA repair inhibition. Toxicol Lett 102:235–239

    PubMed  Google Scholar 

  • Hartwig A (2013) Metal interaction with redox regulation: an integrating concept in metal carcinogenesis? Free Radic Biol Med 55:63–72

    CAS  PubMed  Google Scholar 

  • 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 110:797–799

    CAS  PubMed  PubMed Central  Google Scholar 

  • Hartwig A, Schwerdtle T (2002) Interactions by carcinogenic metal compounds with DNA repair processes: toxicological implications. Toxicol Lett 127:47–54

    CAS  PubMed  Google Scholar 

  • He J, Qian X, Carpenter R, Xu Q, Wang L, Qi Y, Wang Z-X, Liu L-Z, Jiang B-H (2013) Repression of miR-143 mediates Cr (VI)–induced tumor angiogenesis via IGF-IR/IRS1/ERK/IL-8 pathway. Toxicol Sci 134:26–38

    CAS  PubMed  PubMed Central  Google Scholar 

  • Hei TK, Filipic M (2004) Role of oxidative damage in the genotoxicity of arsenic. Free Radic Biol Med 37:574–581

    CAS  PubMed  Google Scholar 

  • Henkler F, Brinkmann J, Luch A (2010) The role of oxidative stress in carcinogenesis induced by metals and xenobiotics. Cancers 2:376–396

    CAS  PubMed  PubMed Central  Google Scholar 

  • Hinhumpatch P, Navasumrit P, Chaisatra K, Promvijit J, Mahidol C, Ruchirawat M (2013) Oxidative DNA damage and repair in children exposed to low levels of arsenic in utero and during early childhood: application of salivary and urinary biomarkers. Toxicol Appl Pharmacol 273:569–579

    CAS  PubMed  Google Scholar 

  • Hodges N, Chipman J (2002) Down-regulation of the DNA-repair endonuclease 8-oxo-guanine DNA glycosylase 1 (hOGG1) by sodium dichromate in cultured human A549 lung carcinoma cells. Carcinogenesis 23:55–60

    CAS  PubMed  Google Scholar 

  • Holmes AL, Wise S, Wise JP Sr (2008) Carcinogenicity of hexavalent chromium. Indian J Med Res

    Google Scholar 

  • Hou L, Zhang X, Wang D, Baccarelli A (2012) Environmental chemical exposures and human epigenetics. Int J Epidemiol 41:79–105

    PubMed  Google Scholar 

  • Hu Y, Jin X, Snow ET (2002) Effect of arsenic on transcription factor AP-1 and NF-κB DNA binding activity and related gene expression. Toxicol Lett 133:33–45

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  • Huang Y, Davidson G, Li J, Yan Y, Chen F, Costa M, Chen LC, Huang C (2002) Activation of nuclear factor-kappaB and not activator protein-1 in cellular response to nickel compounds. Environ Health Perspect 110:835–839

    CAS  PubMed  PubMed Central  Google Scholar 

  • Hubaux R, Becker-Santos DD, Enfield KS, Rowbotham D, Lam S, Lam WL, Martinez VD (2013) Molecular features in arsenic-induced lung tumors. Mol Cancer 12:1–11

    Google Scholar 

  • Inoue M, Sato EF, Nishikawa M, Park A-M, Kira Y, Imada I, Utsumi K (2003) Mitochondrial generation of reactive oxygen species and its role in aerobic life. Curr Med Chem 10:2495–2505

    CAS  PubMed  Google Scholar 

  • Jardim MJ, Fry RC, Jaspers I, Dailey L, Diaz-Sanchez D (2009) Disruption of microRNA expression in human airway cells by diesel exhaust particles is linked to tumorigenesis-associated pathways. Environ Health Perspect 117:1745–1751

    CAS  PubMed  PubMed Central  Google Scholar 

  • Jones R, Brunton V, Frame M (2000) Adhesion-linked kinases in cancer; emphasis on src, focal adhesion kinase and PI 3-kinase. Eur J Cancer 36:1595–1606

    CAS  PubMed  Google Scholar 

  • Kacem S, Feil R (2009) Chromatin mechanisms in genomic imprinting. Mamm Genome 20:544–556

    CAS  PubMed  Google Scholar 

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

    CAS  Google Scholar 

  • Kasten U, Mullenders LH, Hartwig A (1997) Cobalt (II) inhibits the incision and the polymerization step of nucleotide excision repair in human fibroblasts. Mut Res 383:81–89

    CAS  Google Scholar 

  • Keith B, Johnson RS, Simon MC (2012) HIF1α and HIF2α: sibling rivalry in hypoxic tumour growth and progression. Nat Rev Cancer 12:9–22

    CAS  Google Scholar 

  • Kim Y-D, An S-C, Oyama T, Kawamoto T, Kim H (2003) Oxidative stress, hogg1 expression and NF-κB activity in cells exposed to low level chromium. J Occup Health 45:271–277

    CAS  PubMed  Google Scholar 

  • Klaunig JE, Kamendulis LM, Hocevar BA (2010) Oxidative stress and oxidative damage in carcinogenesis. Toxicol Pathol 38:96–109

    CAS  PubMed  Google Scholar 

  • Koedrith P, Kim H, Weon J-I, Seo YR (2013) Toxicogenomic approaches for understanding molecular mechanisms of heavy metal mutagenicity and carcinogenicity. Int J Hyg Environ Health 216:587–598

    CAS  PubMed  Google Scholar 

  • Koedrith P, Seo YR (2011) Advances in carcinogenic metal toxicity and potential molecular markers. Int J Mol Sci 12:9576–9595

    CAS  PubMed  PubMed Central  Google Scholar 

  • Korytowski W, Zareba M, Girotti AW (2000) Inhibition of free radical-mediated cholesterol peroxidation by diazeniumdiolate-derived nitric oxide: effect of release rate on mechanism of action in a membrane system. Chem Res Toxicol 13:1265–1274

    CAS  PubMed  Google Scholar 

  • Lee J-C, Son Y-O, Pratheeshkumar P, Shi X (2012) Oxidative stress and metal carcinogenesis. Free Radic Biol Med 53:742–757

    CAS  PubMed  Google Scholar 

  • Leibeling D, Laspe P, Emmert S (2006) Nucleotide excision repair and cancer. J Mol Histol 37:225–238

    CAS  PubMed  Google Scholar 

  • Lengauer C, Kinzler KW, Vogelstein B (1998) Genetic instabilities in human cancers. Nature 396:643–649

    CAS  PubMed  Google Scholar 

  • Leonard SS, Harris GK, Shi X (2004) Metal-induced oxidative stress and signal transduction. Free Radic Biol Med 37:1921–1942

    CAS  PubMed  Google Scholar 

  • Li G-M (2008) Mechanisms and functions of DNA mismatch repair. Cell Res 18:85–98

    CAS  PubMed  Google Scholar 

  • Linder MC (2012) The relationship of copper to DNA damage and damage prevention in humans. Mut Res 733:83–91

    CAS  Google Scholar 

  • Litwin I, Bocer T, Dziadkowiec D, Wysocki R (2013) Oxidative stress and replication-independent DNA breakage induced by arsenic in Saccharomyces cerevisiae. PLoS Genet 9:e1003640

    CAS  PubMed  PubMed Central  Google Scholar 

  • Liu J, Qu W, Kadiiska MB (2009) Role of oxidative stress in cadmium toxicity and carcinogenesis. Toxicol Appl Pharmacol 238:209–214

    CAS  PubMed  PubMed Central  Google Scholar 

  • Liu L, Li Y, Tollefsbol TO (2008) Gene-environment interactions and epigenetic basis of human diseases. Curr Issues Mol Biol 10:25–36

    CAS  PubMed  Google Scholar 

  • Lu H, Shi X, Costa M, Huang C (2005) Carcinogenic effect of nickel compounds. Mol Cell Biochem 279:45–67

    CAS  PubMed  Google Scholar 

  • Lukiw WJ, Pogue AI (2007) Induction of specific micro RNA (miRNA) species by ROS-generating metal sulfates in primary human brain cells. J Inorg Biochem 101:1265–1269

    CAS  PubMed  PubMed Central  Google Scholar 

  • Macian F, López-Rodríguez C, Rao A (2001) Partners in transcription: NFAT and AP-1. Oncogene 20:2476–2489

    CAS  PubMed  Google Scholar 

  • Mahata J, Chaki M, Ghosh P, Das L, Baidya K, Ray K, Natarajan A, Giri AK (2004) Chromosomal aberrations in arsenic-exposed human populations: a review with special reference to a comprehensive study in West Bengal, India. Cytogenet Genome Res 104:359–364

    CAS  PubMed  Google Scholar 

  • Marsit CJ, Eddy K, Kelsey KT (2006) MicroRNA responses to cellular stress. Cancer Res 66:10843–10848

    CAS  PubMed  Google Scholar 

  • Martinez-Zamudio R, Ha HC (2011) Environmental epigenetics in metal exposure. Epigenetics 6:820–827

    CAS  PubMed  PubMed Central  Google Scholar 

  • Masuda A, Takahashi T (2002) Chromosome instability in human lung cancers: possible underlying mechanisms and potential consequences in the pathogenesis. Oncogene 21:6884–6897

    CAS  PubMed  Google Scholar 

  • Mayo MW, Norris JL, Baldwin AS (2001) Ras regulation of NF-kB and apoptosis. Methods Enzymol 333:73–87

    CAS  PubMed  Google Scholar 

  • McNeill DR, Narayana A, Wong H-K, Wilson DM 3rd (2004) Inhibition of Ape1 nuclease activity by lead, iron, and cadmium. Environ Health Perspect 112:799

    CAS  PubMed  PubMed Central  Google Scholar 

  • Medan D, Luanpitpong S, Azad N, Wang L, Jiang B-H, Davis ME, Barnett JB, Guo L, Rojanasakul Y (2012) Multifunctional role of Bcl-2 in malignant transformation and tumorigenesis of Cr (VI)-transformed lung cells. PLoS One 7:e37045

    CAS  PubMed  PubMed Central  Google Scholar 

  • Meeran SM, Ahmed A, Tollefsbol TO (2010) Epigenetic targets of bioactive dietary components for cancer prevention and therapy. Clin Epigenetics 1:101–116

    CAS  PubMed  PubMed Central  Google Scholar 

  • Mena S, Ortega A, Estrela JM (2009) Oxidative stress in environmental-induced carcinogenesis. Mut Res 674:36–44

    CAS  Google Scholar 

  • Méplan 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 274:31663–31670

    PubMed  Google Scholar 

  • Mishra S, Dwivedi SP, Singh R (2010) A review on epigenetic effect of heavy metal carcinogens on human health. Open Nutraceutic J 3:188

    CAS  Google Scholar 

  • Morse JL, Luczak MW, Zhitkovich A (2013) Chromium (VI) causes interstrand DNA cross-linking in vitro but shows no hypersensitivity in cross-link repair-deficient human cells. Chem Res Toxicol 26:1591–1598

    CAS  PubMed  Google Scholar 

  • Negrini S, Gorgoulis VG, Halazonetis TD (2010) Genomic instability—an evolving hallmark of cancer. Nat Rev Mol Cell Biol 11:220–228

    CAS  PubMed  Google Scholar 

  • Nickens KP, Patierno SR, Ceryak S (2010) Chromium genotoxicity: a double-edged sword. Chem Biol Interact 188:276–288

    CAS  PubMed  PubMed Central  Google Scholar 

  • Novo E, Parola M (2008) Redox mechanisms in hepatic chronic wound healing and fibrogenesis. Fibrogenesis Tissue Repair 1:1–58

    Google Scholar 

  • O’Brien T, Xu J, Patierno SR (2001) Effects of glutathione on chromium-induced DNA. Crosslinking and DNA polymerase arrest. Mol Cell Biochem 222:173–182

    PubMed  Google Scholar 

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

    Google Scholar 

  • Ohshima S (2001) Induction of aneuploidy by nickel sulfate in V79 Chinese hamster cells. Mut Res 492:39–50

    CAS  Google Scholar 

  • Ohshima S (2003) Induction of genetic instability and chromosomal instability by nickel sulfate in V79 Chinese hamster cells. Mutagenesis 18:133–137

    CAS  PubMed  Google Scholar 

  • Okayasu R, Takahashi S, Sato H, Kubota Y, Scolavino S, Bedford JS (2003) Induction of DNA double strand breaks by arsenite: comparative studies with DNA breaks induced by X-rays. DNA Repair 2:309–314

    CAS  PubMed  Google Scholar 

  • Osburn WO, Kensler TW (2008) Nrf2 signaling: an adaptive response pathway for protection against environmental toxic insults. Mut Res 659:31–39

    CAS  Google Scholar 

  • Pande V, Ramos M (2005) NF-κB in human disease: current inhibitors and prospects for de novo structure based design of inhibitors. Curr Med Chem 12:357–374

    CAS  PubMed  Google Scholar 

  • Parasramka MA, Ho E, Williams DE, Dashwood RH (2012) MicroRNAs, diet, and cancer: new mechanistic insights on the epigenetic actions of phytochemicals. Mol Carcinog 51:213–230

    CAS  PubMed  Google Scholar 

  • Pereira S, Cavalie I, Camilleri V, Gilbin R, Adam-Guillermin C (2013) Comparative genotoxicity of aluminium and cadmium in embryonic zebrafish cells. Mut Res 750:19–26

    CAS  Google Scholar 

  • Pierce B, Gao J, Zhang C, Jasmine F, Roy S, Kibriya M, Habibul A (2014). Arsenic exposure, telomere length, and expression of telomere-related genes among Bangladeshi individuals. ISEE Conference Abstracts

    Google Scholar 

  • Pogribny IP, Rusyn I (2013) Environmental toxicants, epigenetics, and cancer. Adv Exp Med Biol 754:215–232

    CAS  PubMed  PubMed Central  Google Scholar 

  • Pogue AI, Li YY, Cui J-G, Zhao Y, Kruck TP, Percy ME, Tarr MA, Lukiw WJ (2009) Characterization of an NF-κB-regulated, miRNA-146a-mediated down-regulation of complement factor H (CFH) in metal-sulfate-stressed human brain cells. J Inorg Biochem 103:1591–1595

    CAS  PubMed  Google Scholar 

  • Poirier LA, Vlasova TI (2002) The prospective role of abnormal methyl metabolism in cadmium toxicity. Environ Health Perspect 110:793–795

    CAS  PubMed  PubMed Central  Google Scholar 

  • Prá D, Franke SIR, Henriques JAP, Fenech M (2012) Iron and genome stability: an update. Mut Res 733:92–99

    Google Scholar 

  • Ren X, McHale CM, Skibola CF, Smith AH, Smith MT, Zhang L (2011) An emerging role for epigenetic dysregulation in arsenic toxicity and carcinogenesis. Environ Health Perspect 119:11–19

    CAS  PubMed  Google Scholar 

  • Rodrigues C, Urbano A, Matoso E, Carreira I, Almeida A, Santos P, Botelho F, Carvalho L, Alves M, Monteiro C (2009) Human bronchial epithelial cells malignantly transformed by hexavalent chromium exhibit an aneuploid phenotype but no microsatellite instability. Mut Res 670:42–52

    CAS  Google Scholar 

  • Rodríguez-Rodero S, Fernández-Morera JL, Fernandez AF, Menendez-Torre E, Fraga MF (2010) Epigenetic regulation of aging. Discov Med 10:225–233

    PubMed  Google Scholar 

  • Rossman TG (1981) Effect of metals on mutagenesis and DNA repair. Environ Health Perspect 40:189–195

    CAS  PubMed  PubMed Central  Google Scholar 

  • Rossman TG (2003) Mechanism of arsenic carcinogenesis: an integrated approach. Mut Res 533:37–65

    CAS  Google Scholar 

  • Rudolf E, Rudolf K, Červinka M (2008) Selenium activates p53 and p38 pathways and induces caspase-independent cell death in cervical cancer cells. Cell Biol Toxicol 24:123–141

    CAS  PubMed  Google Scholar 

  • Salnikow K, Donald SP, Bruick RK, Zhitkovich A, Phang JM, Kasprzak KS (2004) Depletion of intracellular ascorbate by the carcinogenic metals nickel and cobalt results in the induction of hypoxic stress. J Biol Chem 279:40337–40344

    CAS  PubMed  Google Scholar 

  • Salnikow K, Su W, Blagosklonny MV, Costa M (2000) Carcinogenic metals induce hypoxia-inducible factor-stimulated transcription by reactive oxygen species-independent mechanism. Cancer Res 60:3375–3378

    CAS  PubMed  Google Scholar 

  • Salnikow K, Zhitkovich A (2008) Genetic and epigenetic mechanisms in metal carcinogenesis and cocarcinogenesis: nickel, arsenic, and chromium. Chem Res Toxicol 21:28–44

    PubMed  Google Scholar 

  • Schembri F, Sridhar S, Perdomo C, Gustafson AM, Zhang X, Ergun A, Lu J, Liu G, Zhang X, Bowers J (2009) MicroRNAs as modulators of smoking-induced gene expression changes in human airway epithelium. Proc Natl Acad Sci 106:2319–2324

    CAS  PubMed  PubMed Central  Google Scholar 

  • 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 23:432–442

    CAS  PubMed  Google Scholar 

  • Shainkin-Kestenbaum R, Caruso C, Berlyne G (1991) Effect of chromium on oxygen free radical metabolism, inhibition of superoxide dismutase and enhancement of 6-hydroxydopamine oxidation. J Trace Elem Electrolytes Health Dis 5:197–201

    CAS  PubMed  Google Scholar 

  • Sharma M, Sharma S, Arora M, Kaul D (2013) Regulation of cellular cyclin D1 gene by arsenic is mediated through miR-2909. Gene 522:60–64

    CAS  PubMed  Google Scholar 

  • Shen S, Wang C, Weinfeld M, Le XC (2013) Inhibition of nucleotide excision repair by arsenic. Chin Sci Bull 58:214–221

    CAS  Google Scholar 

  • Shi Q, Sutariya V, Bishayee A, Bhatia D (2014) Sequential activation of Elk-1/Egr-1/GADD45α by arsenic. Oncotarget 5:3862

    PubMed  PubMed Central  Google Scholar 

  • Shrivastav M, De Haro LP, Nickoloff JA (2008) Regulation of DNA double-strand break repair pathway choice. Cell Res 18:134–147

    CAS  PubMed  Google Scholar 

  • Silbergeld EK, Waalkes M, Rice JM (2000) Lead as a carcinogen: experimental evidence and mechanisms of action. Am J Ind Med 38:316–323

    CAS  PubMed  Google Scholar 

  • Simeonova PP, Luster MI (2002) Arsenic carcinogenicity: relevance of c-Src activation. Mol Cell Biochem 234:277–282

    PubMed  Google Scholar 

  • Sinha D, Biswas J, Bishayee A (2013) Nrf2-mediated redox signaling in arsenic carcinogenesis: a review. Arch Toxicol 87:383–396

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  • Son Y-O, Pratheeshkumar P, Wang L, Wang X, Fan J, Kim D-H, Lee J-Y, Zhang Z, Lee J-C, Shi X (2013) Reactive oxygen species mediate Cr (VI)-induced carcinogenesis through PI3K/AKT-dependent activation of GSK-3β/β-catenin signaling. Toxicol Appl Pharmacol 271:239–248

    CAS  PubMed  PubMed Central  Google Scholar 

  • Soto-Reyes E, Del Razo LM, Valverde M, Rojas E (2005) Role of the alkali labile sites, reactive oxygen species and antioxidants in DNA damage induced by methylated trivalent metabolites of inorganic arsenic. Biometals 18:493–506

    CAS  PubMed  Google Scholar 

  • Steenland K, Loomis D, Shy C, Simonsen N (1996) Review of occupational lung carcinogens. Am J Ind Med 29:474–490

    CAS  PubMed  Google Scholar 

  • Su LJ, Mahabir S, Ellison GL, McGuinn LA, Reid BC (2012) Epigenetic contributions to the relationship between cancer and dietary intake of nutrients, bioactive food components, and environmental toxicants. Front Genet 2:91

    PubMed  PubMed Central  Google Scholar 

  • Sun H, Zhou X, Chen H, Li Q, Costa M (2009) Modulation of histone methylation and MLH1 gene silencing by hexavalent chromium. Toxicol Appl Pharmacol 237:258–266

    CAS  PubMed  PubMed Central  Google Scholar 

  • Sun X, Zhou X, Du L, Liu W, Liu Y, Hudson LG, Liu KJ (2014) Arsenite binding-induced zinc loss from PARP-1 is equivalent to zinc deficiency in reducing PARP-1 activity, leading to inhibition of DNA repair. Toxicol Appl Pharmacol 274:313–318

    CAS  PubMed  Google Scholar 

  • Sykora P, Snow ET (2008) Modulation of DNA polymerase beta-dependent base excision repair in cultured human cells after low dose exposure to arsenite. Toxicol Appl Pharmacol 228:385–394

    CAS  PubMed  Google Scholar 

  • Thilly WG (2003) Have environmental mutagens caused oncomutations in people? Nat Genet 34:255–259

    CAS  PubMed  Google Scholar 

  • Valko M, Izakovic M, Mazur M, Rhodes CJ, Telser J (2004) Role of oxygen radicals in DNA damage and cancer incidence. Mol Cell Biochem 266:37–56

    CAS  PubMed  Google Scholar 

  • Valko M, Rhodes C, Moncol J, Izakovic M, Mazur M (2006) Free radicals, metals and antioxidants in oxidative stress-induced cancer. Chem Biol Interact 160:1–40

    CAS  PubMed  Google Scholar 

  • 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. Mut Res 654:13–21

    CAS  Google Scholar 

  • Werfel U, Langen V, Eickhoff I, Schoonbrood J, Vahrenholz C, Brauksiepe A, Popp W, Norpoth K (1998) Elevated DNA single-strand breakage frequencies in lymphocytes of welders exposed to chromium and nickel. Carcinogenesis 19:413–418

    CAS  PubMed  Google Scholar 

  • Witkiewicz-Kucharczyk A, Bal W (2006) Damage of zinc fingers in DNA repair proteins, a novel molecular mechanism in carcinogenesis. Toxicol Lett 162:29–42

    CAS  PubMed  Google Scholar 

  • Woźniak K, Błasiak J (2004) Nickel impairs the repair of UV-and MNNG-damaged DNA. Cell Mol Biol Lett 9:83–94

    PubMed  Google Scholar 

  • Wozniak K, Czechowska A, Blasiak J (2006) Nickel (II) affects poly (ADP-ribose) polymerase-mediated DNA repair in normal and cancer cells. Zeitschrift für Naturforschung C 61:142–148

    CAS  Google Scholar 

  • Xia Y, Choi H-K, Lee K (2012) Recent advances in hypoxia-inducible factor (HIF)-1 inhibitors. Eur J Med Chem 49:24–40

    CAS  PubMed  Google Scholar 

  • Yang C, Frenkel K (2002) Arsenic-mediated cellular signal transduction, transcription factor activation, and aberrant gene expression: implications in carcinogenesis. J Environ Pathol Toxicol Oncol 21

    Google Scholar 

  • Yang M (2011) A current global view of environmental and occupational cancers. J Environ Sci Health C 29:223–249

    CAS  Google Scholar 

  • Youn C-K, Kim S-H, Song SH, Chang I-Y, Hyun J-W, Chung M-H, You HJ (2005) Cadmium down-regulates human OGG1 through suppression of Sp1 activity. J Biol Chem 280:25185–25195

    CAS  PubMed  Google Scholar 

  • Yuan C, Kadiiska M, Achanzar WE, Mason RP, Waalkes MP (2000) Possible role of caspase-3 inhibition in cadmium-induced blockage of apoptosis. Toxicol Appl Pharmacol 164:321–329

    CAS  PubMed  Google Scholar 

  • Zhang J, Zhou Y, Ma L, Huang S, Wang R, Gao R, Wu Y, Shi H, Zhang J (2013a) The alteration of miR-222 and its target genes in nickel-induced tumor. Biol Trace Elem Res 152:267–274

    CAS  PubMed  Google Scholar 

  • Zhang J, Zhou Y, Wu Y-J, Li M-J, Wang R-J, Huang S-Q, Gao R-R, Ma L, Shi H-J, Zhang J (2013b) Hyper-methylated miR-203 dysregulates ABL1 and contributes to the nickel-induced tumorigenesis. Toxicol Lett 223:42–51

    CAS  PubMed  Google Scholar 

  • Zhang X, Tang N, Hadden TJ, Rishi AK (2011) Akt, FoxO and regulation of apoptosis. Biochimica et Biophysica Acta (BBA)-molecular. Cell Res 1813:1978–1986

    CAS  Google Scholar 

  • Zhang Y, Bhatia D, Xia H, Castranova V, Shi X, Chen F (2006) Nucleolin links to arsenic-induced stabilization of GADD45α mRNA. Nucleic Acids Res 34:485–495

    CAS  PubMed  PubMed Central  Google Scholar 

  • Zhou X, Li Q, Arita A, Sun H, Costa M (2009) Effects of nickel, chromate, and arsenite on histone 3 lysine methylation. Toxicol Appl Pharmacol 236:78–84

    CAS  PubMed  PubMed Central  Google Scholar 

Download references

Conflicts of Interest

The authors declare no conflicts of interest.

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Author information

Authors and Affiliations

  1. Department of Cellular and Molecular Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran

    Ehsan Ghaedi

  2. Cancer Immunology Project (CIP), Universal Scientific Education and Research Network (USERN), Tehran, Iran

    Ehsan Ghaedi & Mahsa Keshavarz-Fathi

  3. Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA

    Shadi A. Esfahani

  4. Network of Immunity in Infection, Malignancy and Autoimmunity (NIIMA), Universal Scientific Education and Research Network (USERN), Boston, MA, USA

    Shadi A. Esfahani

  5. Research Center for Immunodeficiencies, Children’s Medical Center, Tehran University of Medical Sciences, Tehran, Iran

    Mahsa Keshavarz-Fathi & Nima Rezaei

  6. Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran

    Nima Rezaei

  7. Network of Immunity in Infection, Malignancy and Autoimmunity (NIIMA), Universal Scientific Education and Research Network (USERN), Stockholm, Sweden

    Nima Rezaei

Authors
  1. Ehsan Ghaedi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Shadi A. Esfahani
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Mahsa Keshavarz-Fathi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Nima Rezaei
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Nima Rezaei .

Editor information

Editors and Affiliations

  1. Cancer Immunology Project (CIP), Universal Scientific Education and Research Network (USERN), Stockholm, Sweden

    Nima Rezaei

Rights and permissions

Reprints and permissions

Copyright information

© 2023 The Author(s), under exclusive license to Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Ghaedi, E., Esfahani, S.A., Keshavarz-Fathi, M., Rezaei, N. (2023). Molecular Mechanisms of Metal-Induced Carcinogenesis. In: Rezaei, N. (eds) Cancer Research: An Interdisciplinary Approach. Interdisciplinary Cancer Research, vol 1. Springer, Cham. https://doi.org/10.1007/16833_2023_151

Download citation

Publish with us

Policies and ethics

Search

Navigation