Skip to main content
SpringerLink
Log in

Cadmium Carcinogenesis and Mechanistic Insights

  • Chapter
  • First Online:
Essential and Non-essential Metals

Part of the book series: Molecular and Integrative Toxicology ((MOLECUL))

  • 668 Accesses

Abstract

The heavy metal cadmium is ubiquitous in the environment. Occupational exposures to cadmium have long been linked to cancers of various organs. Emerging epidemiological data, although often limited by study deficits, provide convincing evidence of lung, kidney, prostate, and breast cancers after cadmium exposure. Experimental evidences from animal models and in vitro cell culture systems aid in discerning the molecular pathways of these cancers and provide biological plausibility for cadmium carcinogenesis. The International Agency for Research on Cancer declared cadmium as group I carcinogen with sufficient evidence for cancer in humans. This chapter discusses the molecular pathways of cadmium carcinogenesis for specific organs followed by a brief discussion on general molecular pathways of cadmium-induced carcinogenesis. Finally, conclusions are drawn on the existing database in order to identify common and unique molecular pathways of these cancers and to infer biological plausibility.

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 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
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

Abbreviations

A549:

Human lung epithelial carcinoma cells A549 cells

AR:

Androgen receptor (AR)

Bax:

bcl-2-like protein 4

Bcl-2:

B-cell lymphoma2

Bcl-xL:

B-cell lymphoma-extra-large

BER:

Base excision repair (BER)

CCR4:

C-C chemokine receptor type 4 (CCR4)

CD44:

Cell surface glycoprotein44

CHO:

Chinese hamster Ovary cells

CK8:

Cytokeratin 8

DNMT3b:

DNA methyl transferase3b

EGFR:

Epidermal growth factor receptor

ERCC1:

Excision repair cross-complementing 1

FOXO:

Forkhead box class O

FOXO3a:

Forkhead box class O transcription factor a

GAPDH:

Glyceraldehyde-3-phosphate dehydrogenase

GRP30:

G-protein coupled receptor

GSK3α/β:

Glycogen synthase kinase-3α/

HER2:

Human Epidermal growth factor receptor

hMSH2:

Human mismatch repair protein homologue2

hoGG1:

The human 8-oxoguanine DNA N-glycosylase 1

IARC:

International Agency for Research on Cancer

IL-1β:

Interleukin-1 beta

IL-6:

Interleukin-6

Ki67:

Antigen KI-67

NHANES:

National health and nutrition examination survey

MMR:

Mismatch repair

MMS:

Methyl methane sulfonate

MNU:

N-methyl -N-nitrosourea

MT:

Metallothionein

NER:

Nucleotide excision pathway (NER)

NKX3.1:

Homeobox protein NKX3.1

Nrf2 :

Nuclear factor (erythroid-derived 2)-like 2’

OCT4:

Octamer-binding transcription factor 4

P53:

Tumor suppressor protein p53

PI3K:

Phosphoinositide-3-kinase

PSA:

prostate-specific antigen

PSCA:

Prostate stem cell antigen

RSK2:

Ribosomal s6 kinase 2

ROS:

Reactive oxygen species (ROS)

S100P:

S100 calcium-binding protein P

SCID mice:

The severe combined immunodeficiency mice

SPCA:

Secretory pathway Ca-ATPase

TNF-α:

Tumor necrosis factor-alpha

XIAP:

X-linked inhibitor of apoptosis protein

XPA:

Xeroderma Pigmentosum group A protein

XPC:

Xeroderma pigmentosum, complementation group C protein

XRCC1:

X-ray repair cross-complementing protein 1

References

  1. IARC. IARC monograph on cadmium and cadmium compounds. Lyon: IARC; 2012. http://monographs.iarc.fr/ENG/Monographs/vol100C/mono100C-8.pdf.

  2. Waalkes MP. Cadmium carcinogenesis in review. J Inorg Biochem. 2000;79(1-4):241–4.

    Article  CAS  PubMed  Google Scholar 

  3. Nawrot T, Plusquin M, Hogervorst J, et al. Environmental exposure to cadmium and risk of cancer: a prospective population-based study. Lancet Oncol. 2006;7:119–26.

    Article  CAS  PubMed  Google Scholar 

  4. Park RM, Stayner LT, Petersen MR, et al. Cadmium and lung cancer mortality accounting for simultaneous arsenic exposure. Occup Environ Med. 2012;69(5):303–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Lei YX, Wei L, Wang M, et al. Malignant transformation and abnormal expression of eukaryotic initiation factor in bronchial epithelial cells induced by cadmium chloride. Biomed Environ Sci. 2008;21(4):332–8.

    Article  CAS  PubMed  Google Scholar 

  6. Person RJ, Tokar EJ, Xu Y, et al. Chronic cadmium exposure in vitro induces cancer cell characteristics in human lung cells. Toxicol Appl Pharmacol. 2013;273(2):281–8.

    Article  CAS  PubMed  Google Scholar 

  7. Waalkes MP. Cadmium carcinogenesis. Mutat Res. 2003;533(1-2):107–20.

    Article  CAS  PubMed  Google Scholar 

  8. Zhou Z, Wang C, Liu H, et al. Cadmium induced cell apoptosis, DNA damage, decreased DNA repair capacity, and genomic instability during malignant transformation of human bronchial epithelial cells. Int J Med Sci. 2013;10(11):1485–96.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  9. Lag M, Westly S, Lerstad T, et al. Cadmium-induced apoptosis of primary epithelial lung cells: Involvement of Bax and p53, but not of oxidative stress. Cell Biol Toxicol. 2002;18(1):29–42.

    Article  CAS  PubMed  Google Scholar 

  10. Mowers EE, Sharifi MN, Macleod KF. Autophagy in cancer metastasis. Oncogene. 2016;36(12):1619–30. doi:10.1038/onc.2016.333.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  11. Kenific CM, Debnath J. Cellular and metabolic functions for autophagy in cancer cells. Trends Cell Biol. 2015;25(1):37–45.

    Article  CAS  PubMed  Google Scholar 

  12. Yo S, Wang X, Hitron JA. Cadmium induces autophagy through ROS-dependent activation of the LKB1-AMPK signaling in skin epidermal cells. Toxicol Appl Pharmacol. 2011;255(3):287–96.

    Article  CAS  Google Scholar 

  13. Park CH, Lee BH, Ahn SG, et al. Serine 9 and Tyrosine 216 phosphorylation of GSK-3β differentially regulates autophagy in acquired cadmium resistance. Toxicol Sci. 2013;135(2):380–9.

    Article  CAS  PubMed  Google Scholar 

  14. Kim HR, Lee KY, Ahn SG, et al. Transcriptional regulation, stabilization, and subcellular redistribution of multidrug resistance-associated protein 1 (MRP1) by glycogen synthase kinase 3αβ: novel insights on modes of cadmium-induced cell death stimulated by MRP1. Arch Toxicol. 2015;89(8):1271–84.

    Article  CAS  PubMed  Google Scholar 

  15. Son YO, Pratheeshkumar P, Roy RV, et al. Nrf2/p62 signaling in apoptosis resistance and its role in cadmium-induced carcinogenesis. J Biol Chem. 2014;289(41):28660–75.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Kundu S, Sengupta S, Chatterjee S, et al. Cadmium induces lung inflammation independent of lung cell proliferation: a molecular approach. J Inflamm (Lond). 2009;6:6–19.

    Article  Google Scholar 

  17. Kundu S, Sengupta S, Bhattacharyya A. EGFR upregulates inflammatory and proliferative responses in human lung adenocarcinoma cell line (A549), induced by lower dose of cadmium chloride. Inhal Toxicol. 2011;23(6):339–48.

    Article  CAS  PubMed  Google Scholar 

  18. Kalish LH, Kwong RA, Cole IE, et al. Deregulated cyclin D1 expression is associated with decreased efficacy of the selective epidermal growth factor receptor tyrosine kinase inhibitor gefitinib in head and neck squamous cell carcinoma cell lines. Clin Cancer Res. 2004;10(22):7764–74.

    Article  CAS  PubMed  Google Scholar 

  19. Waalkes MP, Klassen CD. Concentration of metallothionein in major organs of rats after administration of various metals. Fundam Appl Toxicol. 1985;5(3):473–7.

    Article  CAS  PubMed  Google Scholar 

  20. Bridges CC, Zalups RK. Molecular and ionic mimicry and the transport of toxic metals. Toxicol Appl Pharmacol. 2005;204(3):274–308.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. He L, Wang B, Hay EB, et al. Discovery of ZIP transporters that participate in cadmium damage to testis and kidney. Toxicol Appl Pharmacol. 2009;238(3):250–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Jin T, Lu J, Nordberg M. Toxicokinetics and biochemistry of cadmium with special emphasis on the role of metallothionein. Neurotoxicology. 1998;19(4-5):529–35.

    CAS  PubMed  Google Scholar 

  23. Klassen CD, Liu J, Diwan BA. Metallothionein protection of cadmium toxicity. Toxicol Appl Pharmacol. 2009;238:215–20.

    Article  CAS  Google Scholar 

  24. Goyer R A, Fowler BA, Nordberg GF, Shepard G, Moustafa L, editors. Proceedings of the Metallothionein and Cadmium Nephrotoxicity Conference 1983, Environ Health Perspect. 1984;54:1–295.

    Google Scholar 

  25. Klassen CD, Liu J. Induction of metallothionein as an adaptive mechanism affecting the magnitude and progression of toxicological injury. Environ Health Perspect. 1998;106:297–300.

    Article  Google Scholar 

  26. Huff J, Lunn RM, Waalkes MP, et al. Cadmium-induced cancers in animals and in humans. Int J Occup Environ Health. 2007;13(2):202–12.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Kaewnate Y, Niyomtam S, Tangvarasittichai O, et al. Association of elevated urinary cadmium with urinary stone, hypercalciuria and renal tubular dysfunction in the population of cadmium-contaminated area. Bull Environ Contam Toxicol. 2012;89(6):1120–4.

    Article  CAS  PubMed  Google Scholar 

  28. Suwazono Y, Nogawa K, Morikawa Y, et al. Renal tubular dysfunction increases mortality in the Japanese general population living in cadmium non-polluted areas. J Expo Sci Environ Epidemiol. 2015;25(4):399–404.

    Article  CAS  PubMed  Google Scholar 

  29. Hamada T, Nakano S, Iwai S, et al. Pathological study on beagles after long-term oral administration of cadmium. Toxicol Pathol. 1991;19(2):138–47.

    Article  CAS  PubMed  Google Scholar 

  30. Tanimoto A, Hamada T, Koide O. Cell death and regeneration of renal proximal tubular cells in rats with sub chronic cadmium intoxication. Toxicol Pathol. 1993;21(4):341–52.

    Article  CAS  PubMed  Google Scholar 

  31. Tanimoto A, Hamada T, Higashi K, et al. Distribution of cadmium and metallothionein in CdCl2-exposed rat kidney: relationship with apoptosis and regeneration. Pathol Int. 1999;49(2):125–32.

    Article  CAS  PubMed  Google Scholar 

  32. Yan H, Carter CE, Xu C, et al. Cadmium-induced apoptosis in the urogenital organs of the male rat and its suppression by chelation. J Toxicol Environ Health. 1997;52(2):149–68.

    Article  CAS  PubMed  Google Scholar 

  33. Hamada T, Tanimoto A, Sasaguri Y. Apoptosis induced by cadmium. Apoptosis. 1997;2(4):359–67.

    Article  CAS  PubMed  Google Scholar 

  34. Aoyagi T, Hayakawa K, Miyaji K, et al. Cadmium nephrotoxicity and evacuation from the body in a rat modeled subchronic intoxication. Int J Urol. 2003;10(6):332–8.

    Article  CAS  PubMed  Google Scholar 

  35. Prozialeck WC, Edwards JR, Lamar PC, et al. Expression of kidney injury molecule-1 (Kim-1) in relation to necrosis and apoptosis during the early stages of Cd-induced proximal tubule injury. Toxicol Appl Pharmacol. 2009;238(3):306–14.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Chargui A, Zekri S, Jacquillet G, et al. Cadmium-induced autophagy in rat kidney: an early biomarker of subtoxic exposure. Toxicol Sci. 2011;121(1):31–42.

    Article  CAS  PubMed  Google Scholar 

  37. Liu Y, Templeton DM. Initiation of caspase-independent death in mouse mesangial cells by Cd2+: involvement of p38 kinase and CaMK-II. J Cell Physiol. 2008;217(2):307–18.

    Article  CAS  PubMed  Google Scholar 

  38. Xiao W, Liu Y, Templeton DM, et al. Pleiotropic effects of cadmium in mesangial cells. Toxicol Appl Pharmacol. 2009;238(3):315–26.

    Article  CAS  PubMed  Google Scholar 

  39. Chen L, Xu B, Liu L, Luo Y, et al. Cadmium induction of reactive oxygen species activates the mTOR pathway, leading to neuronal cell death. Free Radic Biol Med. 2011;50(5):624–32.

    Article  CAS  PubMed  Google Scholar 

  40. Son YO, Wang L, Poyil P, et al. Cadmium induces carcinogenesis in BEAS-2B cells through ROS-dependent activation of PI3K/AKT/GSK-3β/β-catenin signaling. Toxicol Appl Pharmacol. 2012;264(2):153–60.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Fujiki K, Inamura H, Matsuoka M. Phosphorylation of FOXO3a by PI3K/Akt pathway in HK-2 renal proximal tubular epithelial cells exposed to cadmium. Arch Toxicol. 2013;87(12):2119–27.

    Article  CAS  PubMed  Google Scholar 

  42. Fujiki K, Inamura H, Matsuoka M. PI3K signaling mediates diverse regulation of ATF4 expression for the survival of HK-2 cells exposed to cadmium. Arch Toxicol. 2014;88(2):403–14.

    Article  CAS  PubMed  Google Scholar 

  43. Dansen TB, Burgering B. Unravelling the tumor-suppressive functions of FOXO proteins. Trends Cell Biol. 2008;18(9):421–9.

    Article  CAS  PubMed  Google Scholar 

  44. Prozialeck WC, Edwards JR. Cell adhesion molecules in chemically induced renal injury. Pharmacol Ther. 2007;14:74–93.

    Article  CAS  Google Scholar 

  45. Parrish AR, Prozialeck WC. Metals and cell adhesion molecules. In: Koropatkick J, Zalups RK, editors. Cellular and molecular biology of metals. Oxford: Taylor & Francis; 2010. p. 327–50.

    Chapter  Google Scholar 

  46. Prozialeck WC, Lamar PC, Lynch SM. Cadmium alters the localization of N-cadherin, E-cadherin, and beta-catenin in the proximal tubule epithelium. Toxicol Appl Pharmacol. 2003;189(3):180–95.

    Article  CAS  PubMed  Google Scholar 

  47. Prozialeck WC, Lamar PC, Appelt DM. Differential expression of E-cadherin, N-cadherin and beta-catenin in proximal and distal segments of the rat nephron. BMC Physiol. 2004;4:10. doi:10.1186/1472-6793-4-10.

    Article  PubMed  PubMed Central  Google Scholar 

  48. Molitoris BA, Marrs J. The role of cell adhesion molecules in ischemic acute renal failure. Am J Med. 1999;106:583–92.

    Article  CAS  PubMed  Google Scholar 

  49. Sabolić I, Herak-Kramberger CM, Brown D. Sub chronic cadmium treatment affects the abundance and arrangement of cytoskeletal proteins in rat renal proximal tubule cells. Toxicology. 2001;165(2-3):205–16.

    Article  PubMed  Google Scholar 

  50. Sabolic I, Herak-Kramberger CM, Antolovic R, et al. Loss of basolateral invaginations in proximal tubules of cadmium-intoxicated rats is independent of microtubules and clathrin. Toxicology. 2006;218:149–63.

    Article  CAS  PubMed  Google Scholar 

  51. Chakraborty PK, Scharner B, Jurasovic J, et al. Chronic cadmium exposure induces transcriptional activation of the Wnt pathway and upregulation of epithelial-to-mesenchymal transition markers in mouse kidney. Toxicol Lett. 2010;198:69–76.

    Article  CAS  PubMed  Google Scholar 

  52. Yin L, Velazquez OC, Liu ZJ. Notch signaling: emerging molecular targets for cancer therapy. Biochem Pharmacol. 2010;80(5):690–701.

    Article  CAS  PubMed  Google Scholar 

  53. Fujiki K, Inamura H, Matsuoka M. Detrimental effects of Notch1 signaling activated by cadmium in renal proximal tubular epithelial cells. Cell Death Dis. 2014;5:e1378.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Zhang L, Zhu Y, Hao R, et al. Cadmium levels in tissue and plasma as a risk factor for prostate carcinoma: a meta-analysis. Biol Trace Elem Res. 2015;172(1):86–92.

    Article  PubMed  CAS  Google Scholar 

  55. Waalkes MP, Rehm S, Riggs CW, et al. Cadmium carcinogenesis in male Wistar [Crl:(WI)BR] rats: dose-response analysis of tumor induction in the prostate and testes and at the injection site. Cancer Res. 1988;48(16):4656–63.

    CAS  PubMed  Google Scholar 

  56. Waalkes MP, Rehm S, Riggs CW, et al. Cadmium carcinogenesis in male Wistar [Crl: (WI)BR] rats: dose-response analysis of effects of zinc on tumor induction in the prostate, in the testes, and at the injection site. Cancer Res. 1989;49(15):4282–8.

    CAS  PubMed  Google Scholar 

  57. Waalkes MP, Anver M, Diwan BA. Carcinogenic effects of cadmium in the noble (NBL/Cr) rat: induction of pituitary, testicular, and injection site tumors and intraepithelial proliferative lesions of the dorsolateral prostate. Toxicol Sci. 1999;52(2):154–61.

    Article  CAS  PubMed  Google Scholar 

  58. Waalkes MP, Anver MR, Diwan BA. Chronic toxic and carcinogenic effects of oral cadmium in the Noble (NBL/Cr) rat: induction of neoplastic and proliferative lesions of the adrenal, kidney, prostate, and testes. J Toxicol Environ Health A. 1999;58(4):199–214.

    Article  CAS  PubMed  Google Scholar 

  59. Nakamura K, Yasunaga Y, Ko D. Cadmium-induced neoplastic transformation of human prostate epithelial cells. Int J Oncol. 2002;20(3):543–7.

    CAS  PubMed  Google Scholar 

  60. Zhou T, Zhou G, Song W. Cadmium-induced apoptosis and changes in expression of p53, c-jun and MT-I genes in testes and ventral prostate of rats. Toxicology. 1999;142(1):1–13.

    Article  CAS  PubMed  Google Scholar 

  61. Achanzar WE, Achanzar KB, Lewis JG, et al. Cadmium induces c-myc, p53, and c-jun expression in normal human prostate epithelial cells as a prelude to apoptosis. Toxicol Appl Pharmacol. 2000;164(3):291–300.

    Article  CAS  PubMed  Google Scholar 

  62. Qu W, Ke H, Pi J, et al. 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. 2007;115(7):1094–100.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Aimola P, Carmignani M, Volpe AR, et al. Cadmium induces p53-dependent apoptosis in human prostate epithelial cells. PLoS One. 2012;7(3), e33647.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. El-Atta HM, El-Bakary AA, Attia AM, et al. DNA fragmentation, caspase 3 and prostate-specific antigen genes expression induced by arsenic, cadmium, and chromium on non-tumorigenic human prostate cells. Biol Trace Elem Res. 2014;162(1-3):95–105.

    Article  CAS  PubMed  Google Scholar 

  65. Martín JJ, Martín R, Codesal J, et al. Cadmium chloride-induced dysplastic changes in the ventral rat prostate: an immune histochemical and quantitative study. Prostate. 2001;46(1):​11–20.

    Article  PubMed  Google Scholar 

  66. Arriazu R, Pozuelo JM, Henriques-Gil N, et al. Immunohistochemical study of cell proliferation, Bcl-2, p53, and caspase-3 expression on pre-neoplastic changes induced by cadmium and zinc chloride in the ventral rat prostate. J Histochem Cytochem. 2005;54(9):981–90.

    Article  CAS  Google Scholar 

  67. Arriazu R, Durán E, Pozuelo JM. Expression of lysophosphatidic acid receptor 1 and relation with cell proliferation, apoptosis, and angiogenesis on pre-neoplastic changes induced by cadmium chloride in the rat ventral prostate. PLoS One. 2013;8(2), e57742.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Bakshi S, Zhang X, Godoy-Tundidor S, et al. Transcriptome analyses in normal prostate epithelial cells exposed to low-dose cadmium: oncogenic and immunomodulations involving the action of tumor necrosis factor. Environ Health Perspect. 2008;116(6):769–76.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Golovine K, Makhov P, Uzzo RG, et al. Cadmium down-regulates expression of XIAP at the post-transcriptional level in prostate cancer cells through an NF-kappaβ-independent, proteasome-mediated mechanism. Mol Can. 2010;9:183–93.

    Article  CAS  Google Scholar 

  70. Julin B, Wolk A, Bergkvist L, et al. Dietary cadmium exposure and risk of postmenopausal breast cancer: a population-based prospective cohort study. Cancer Res. 2012;72(6):​1459–66.

    Article  CAS  PubMed  Google Scholar 

  71. Van Maele-Fabry G, Lombaert N, Lison D. Dietary exposure to cadmium and risk of breast cancer in postmenopausal women: A systematic review and meta-analysis. Environ Int. 2016;86:1–13.

    Article  PubMed  CAS  Google Scholar 

  72. McElroy JA, Shafer MM, Trentham-Dietz A, et al. Cadmium exposure and breast cancer risk. J Natl Cancer Inst. 2006;98(12):869–73.

    Article  CAS  PubMed  Google Scholar 

  73. Gallagher CM, Chen JJ, Kovach JS. Environmental cadmium and breast cancer risk. Aging (Albany NY). 2010;2(11):804–14.

    Article  CAS  Google Scholar 

  74. Nagata C, Nagao Y, Nakamura Y, et al. Cadmium exposure and the risk of breast cancer in Japanese women. Breast Cancer Res Treat. 2013;138(1):235–9.

    Article  CAS  PubMed  Google Scholar 

  75. Strumylaite L, Kregzdyte R, Bogusevicius A, et al. Association between cadmium and breast cancer risk according to estrogen receptor and human epidermal growth factor receptor 2: epidemiological evidence. Breast Cancer Res Treat. 2014;145(1):225–32.

    Article  CAS  PubMed  Google Scholar 

  76. Romanowicz-Makowska H, Forma E, Bryś M, et al. Concentration of cadmium, nickel and aluminium in female breast cancer. Pol J Pathol. 2011;62(4):257–61.

    CAS  PubMed  Google Scholar 

  77. Ionescu JG, Novotny J, Stejskal V, et al. Increased levels of transition metals in breast cancer tissue. Neuro Endocrinol Lett. 2006;27 Suppl 1:36–9.

    CAS  PubMed  Google Scholar 

  78. Mohammadi M, Riyahi Bakhtiari A, Khodabandeh S, et al. Concentration of Cd, Pb, Hg, and Se in different parts of human breast cancer tissues. J Toxicol. 2014;2014:413870. doi:10.1155/2014/413870.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  79. Larsson SC, Orsini N, Wolk A. Urinary cadmium concentration and risk of breast cancer: a systematic review and dose-response meta-analysis. Am J Epidemiol. 2015;182(5):375–80.

    Article  PubMed  Google Scholar 

  80. Kippler M, Lönnerdal B, Goessler W. Cadmium interacts with the transport of essential micronutrients in the mammary gland—a study in rural Bangladeshi women. Toxicology. 2009;257(1-2):64–9.

    Article  CAS  PubMed  Google Scholar 

  81. Adams SV, Newcomb PA, Shafer MM, et al. Urinary cadmium and mammographic density in premenopausal women. Breast Cancer Res Treat. 2011;128(3):837–44.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Ohrvik H, Ullerås E, Oskarsson A, et al. Effects of cadmium on calcium transporter SPCA, calcium homeostasis and β-casein expression in the murine mammary epithelium. Toxicol Lett. 2011;201(1):80–5.

    Article  CAS  PubMed  Google Scholar 

  83. Lönnerdal B. Trace element transport in the mammary gland. Annu Rev Nutr. 2007;27:165–77.

    Article  PubMed  CAS  Google Scholar 

  84. Ohrvik H, Thiele DJ. How copper traverses cellular membranes through the mammalian copper transporter 1, Ctr1. Ann N Y Acad Sci. 2014;1314:32–41.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Aquino NB, Sevigny MB, Sabangan J, et al. The role of cadmium and nickel in estrogen receptor signaling and breast cancer: metallo-estrogens or not? J Environ Sci Health C Environ Carcinog Ecotoxicol Rev. 2012;30(3):189–224.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Silva N, Peiris-John R, Wickremasinghe R, et al. Cadmium a metallo-estrogen: are we convinced? J Appl Toxicol. 2012;32(5):318–32.

    Article  CAS  PubMed  Google Scholar 

  87. Garcia-Morales P, Saceda M, Kenney N. Effect of Cadmium on estrogen receptor levels and estrogen-induced responses in human breast cancer cells. J Biol Chem. 1994;269(24):​16896–901.

    CAS  PubMed  Google Scholar 

  88. Stoica A, Katzenellenbogen BS, Martin MB. Activation of estrogen receptor-alpha by the heavy metal cadmium. Mol Endocrinol. 2000;14(4):545–53.

    CAS  PubMed  Google Scholar 

  89. Wilson VS, Bobseine K, Gray Jr LE. Development and characterization of a cell line that stably expresses an estrogen-responsive luciferase reporter for the detection of estrogen receptor agonist and antagonists. Toxicol Sci. 2004;81:69–77.

    Article  CAS  PubMed  Google Scholar 

  90. Brama M, Gnessi L, Basciani S, Cerulli N, et al. Cadmium induces mitogenic signaling in breast cancer cell by an ER alpha-dependent mechanism. Mol Cell Endocrinol. 2007;264(1-2):102–891.

    Article  CAS  PubMed  Google Scholar 

  91. Siewit CL, Gengler B, Vegas E, et al. Cadmium promotes breast cancer cell proliferation by potentiating the interaction between ER alpha and c-Jun. Mol Endocrinol. 2010;24(5):981–92.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Sun X, Fontaine JM. Bartl I. Induction of Hsp22 (HspB8) by estrogen and the metallo-estrogen cadmium in estrogen receptor-positive breast cancer cells. Cell Stress Chaperones. 2007 Winter;12(4):307–19.

    Google Scholar 

  93. Sirchia R, Longo A, Luparello C. Cadmium regulation of apoptotic and stress response genes in tumoral and immortalized epithelial cells of the human breast. Biochimie. 2008;90(10):1578–90.

    Article  CAS  PubMed  Google Scholar 

  94. Casano C, Sirchia R, et al. Cadmium effects on p38/MAPK isoforms in MDA-MB231 breast cancer cells. Biometals. 2010;3(1):83–92.

    Article  CAS  Google Scholar 

  95. Martínez-Campa CM, Alonso-González C, Mediavilla MD, et al. Melatonin down-regulates hTERT expression induced by either natural estrogens (17beta-estradiol) or metallo-estrogens (cadmium) in MCF-7 human breast cancer cells. Cancer Lett. 2008;268(2):272–7.

    Article  PubMed  CAS  Google Scholar 

  96. Pilav ZL, Borras DM, Ponce E, et al. Using expression profiling to understand the effects of chronic cadmium exposure on MCF-7 breast cancer cells. PLoS One. 2013;8(12), e84646.

    Article  CAS  Google Scholar 

  97. Zang Y, Odwin-Dacosta S, Yager JD, et al. Effects of cadmium on estrogen receptor mediated signaling and estrogen induced DNA synthesis in T47D human breast cancer cells. Toxicol Lett. 2009;184(2):134–8.

    Article  CAS  PubMed  Google Scholar 

  98. Song X, Wei Z, Shaikh ZA. Requirement of ERα and basal activities of EGFR and Src kinase in Cd-induced activation of MAPK/ERK pathway in human breast cancer MCF-7 cells. Toxicol Appl Pharmacol. 2015;287(1):26–34.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Johnson MD, Kenney N, Stoica A, et al. Cadmium mimics the in vivo effects of estrogen in the uterus and mammary gland. Nat Med. 2003;9(8):1081–4.

    Article  CAS  PubMed  Google Scholar 

  100. Alonso-González C, González A, Mazarrasa O. Melatonin prevents the estrogenic effects of sub-chronic administration of cadmium on mice mammary glands and uterus. J Pineal Res. 2007;42(4):403–10.

    Article  PubMed  CAS  Google Scholar 

  101. Liu J, Huang H, Zhang W. Cadmium-induced increase in uterine wet weight and its mechanism. Birth Defects Res B Dev Reprod Toxicol. 2010;89(1):43–9.

    CAS  PubMed  Google Scholar 

  102. Ali I, Penttinen-Damdimopoulou PE, Mäkelä SI. Estrogen-like effects of cadmium in vivo do not appear to be mediated via the classical the classical estrogen receptor transcriptional pathway. Environ Health Perspect. 2010;118(10):1389–94.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Yu X, Filardo EJ, Shaikh ZA. The membrane estrogen receptor GPR30 mediates cadmium-induced proliferation of breast cancer cells. Toxicol Appl Pharmacol. 2010;245(1):83–90.

    Article  CAS  PubMed  Google Scholar 

  104. Ariazi EA, Brailoiu E, Yerrum SS, et al. The G protein-coupled receptor GPR30 inhibits proliferation of estrogen receptor-positive breast cancer cells. Cancer Res. 2010;70(3):​1184–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  105. Strumylaite L, Bogusevicius A, Abdrachmanovas O. Cadmium concentration in biological media of breast cancer patients. Breast Cancer Res Treat. 2011;125(2):511–7.

    Article  CAS  PubMed  Google Scholar 

  106. Prozialeck WC. Evidence that E-cadherin may be a target for cadmium toxicity in epithelial cells. Toxicol Appl Pharmacol. 2000;164(3):231–49.

    Article  CAS  PubMed  Google Scholar 

  107. Prozialeck WC, Edwards JR. Mechanisms of cadmium-induced proximal tubule injury: new insights with implications for biomonitoring and therapeutic interventions. J Pharmacol Exp Ther. 2012;343(1):2–12.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  108. Thevenod F. Cadmium and cellular signaling cascades: to be or not to be? Toxicol Appl Pharmacol. 2009;238(3):221–39.

    Article  CAS  PubMed  Google Scholar 

  109. Mann B, Gelos M, Siedow A, et al. Target genes of beta catenin-T cell-factor/lymphoid-enhancer-factor signaling in human colorectal carcinomas. Proc Natl Acad Sci U S A. 1999;96(4):1603–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  110. Crawford HC, Fingleton BM, Rudolph-Owen LA, et al. The metalloproteinase matrilysin is a target of beta-catenin transactivation in intestinal tumors. Oncogene. 1999;8(18):​2883–91.

    Article  CAS  Google Scholar 

  111. Knirsh R, Ben-Dror I, Spangler B, et al. Loss of E-cadherin-mediated cell-cell contacts activates a novel mechanism for up-regulation of the proto-oncogene c-Jun. Mol Biol Cell. 2009;20(7):2121–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  112. Thévenod F, Wolff NA, Bork U. Cadmium induces nuclear translocation of beta-catenin and increases expression of c-myc and Abcb1a in kidney proximal tubule cells. Biometals. 2007;20(5):807–20.

    Article  PubMed  CAS  Google Scholar 

  113. Kuphal S, Poser I, Jobin C. Loss of E-cadherin leads to upregulation of NFkappa B activity in malignant melanoma. Oncogene. 2004;23(52):8509–19.

    Article  CAS  PubMed  Google Scholar 

  114. Pearson CA, Prozialeck WC. E-Cadherin, beta-catenin and cadmium carcinogenesis. Med Hypotheses. 2001;56(5):573–81.

    Article  CAS  PubMed  Google Scholar 

  115. Park CS, Kim OS, Yun SM. Presenilin 1/gamma-secretase is associated with cadmium-induced E-cadherin cleavage and COX-2 gene expression in T47D breast cancer cells. Toxicol Sci. 2008;106(2):413–22.

    Article  CAS  PubMed  Google Scholar 

  116. Ponce E, Louie MC, Sevigny MB, et al. Acute and chronic cadmium exposure promotes E-cadherin degradation in MCF7 breast cancer cells. Mol Carcinog. 2015;54(10):1014–25.

    Article  CAS  PubMed  Google Scholar 

  117. Barrett JR. A potential window onto early pancreatic cancer development: evidence of cancer-stem cell growth after exposure to cadmium chloride in vitro. Environ Health Perspect. 2012;120(9):A363.

    Article  PubMed  PubMed Central  Google Scholar 

  118. Eneman JD, Potts RJ, Osier M, et al. Suppressed oxidant-induced apoptosis in cadmium adapted alveolar epithelial cells and its potential involvement in cadmium carcinogenesis. Toxicology. 2000;147(3):215–28.

    Article  CAS  PubMed  Google Scholar 

  119. Ochi T, Ohsawa M. Participation of active oxygen species in the induction of chromosomal aberrations by Cadmium. Mutat Res. 1985;143(3):137–42.

    Article  CAS  PubMed  Google Scholar 

  120. Filipic M, Hei TK. Mutagenicity of Cadmium in mammalian cells: implications of oxidative DNA damage. Mut Res. 2004;546(1-2):81–91.

    Article  CAS  Google Scholar 

  121. Potts RJ, Bespalov IA, Wallace SS, et al. Inhibition of oxidative DNA repair in cadmium-adapted alveolar epithelial cells and the potential involvement of metallothionein. Toxicology. 2001;161(1-2):25–38.

    Article  CAS  PubMed  Google Scholar 

  122. Hengstler J, Audorff UB, Faldum A. Occupational exposures 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. 2003;24(1):63–73.

    Article  CAS  PubMed  Google Scholar 

  123. Hirano T, Yamaguchi Y, Kasai H, et al. Inhibition of 8-hydroxyguanine repair in testes after administration of cadmium chloride to GSH-depleted rats. Toxicol Appl Pharmacol. 1997;147(1):9–14.

    Article  CAS  PubMed  Google Scholar 

  124. Candéias S, Pons B, Viau M, et al. Direct inhibition of excision/synthesis DNA repair activities by cadmium: analysis on dedicated biochips. Mutat Res. 2010;94(1-2):53–9.

    Article  CAS  Google Scholar 

  125. Hamann I, König C, Richter C, et al. impact of cadmium on hOGG1 and APE1 as a function of the cellular p53 status. Mutat Res. 2012;736(1-2):56–63.

    Article  CAS  PubMed  Google Scholar 

  126. Bravard A, Campalans A, Vacher M. 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. 2010;685(1-2):61–9.

    Article  CAS  PubMed  Google Scholar 

  127. Hartmann M, Hartwig A. Disturbance of DNA damage recognition after UV-irradiation by nickel(II) and cadmium(II) in mammalian cells. Carcinogenesis. 1998;19:617–21.

    Article  CAS  PubMed  Google Scholar 

  128. Fatur T, Lah TT, Filipic M. Cadmium inhibits repair of UV-, methyl methanesulfonate- and N-methyl-N-nitrosourea-induced DNA damage in Chinese hamster ovary cells. Mutat Res. 2003;529(1-2):109–16.

    Article  CAS  PubMed  Google Scholar 

  129. Schwerdtle T, Ebert F, Thuy C, et al. Genotoxicity of soluble and particulate cadmium compounds: impact on oxidative DNA damage and nucleotide excision repair. Chem Res Toxicol. 2010;23(2):432–42.

    Article  CAS  PubMed  Google Scholar 

  130. Meplan C, Mann K, Hainaut P. Cadmium induces conformational modifications of wild-type p53 and suppresses p53 response to DNA damage in cultured cells. J Boil. 1999;274:​31663–70.

    Article  CAS  Google Scholar 

  131. Adimoolam S, Ford JM. p53 and DNA damage-inducible expression of the Xeroderma pigmentosum group C gene. Proc Natl Acad Sci U S A. 2002;99(20):12985–90.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  132. Jin YH, Clark AB, Slebos RJ, et al. Cadmium is a mutagen that acts by inhibiting mismatch repair. Nat Genet. 2003;34(3):326–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  133. Filipic M. Mechanisms of cadmium induced genomic stability. Mutat Res. 2012;733(1-2):​69–77.

    Article  CAS  PubMed  Google Scholar 

  134. Clark AB, Kunkel TA. Cadmium inhibits the functions of eukaryotic MutS complexes. J Biol Chem. 2004;279(52):53903–6.

    Article  CAS  PubMed  Google Scholar 

  135. Lützen A, Rasmussen LJ, Liberti SE. Cadmium inhibits human DNA mismatch repair in vivo. Biochem Biophys Res Commun. 2004;321(1):21–5.

    Article  PubMed  CAS  Google Scholar 

  136. Banerjee S, Flores-Rozas H. Cadmium inhibits mismatch repair by blocking the ATPase activity of the MSH-2 MSH-6 complex. Nucleic Acids Res. 2005;33(4):1410–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  137. Wieland M, Levin MK, Hingorani KS, et al. Mechanism of cadmium-mediated inhibition of Msh2-Msh6 function in DNA mismatch repair. Biochemistry. 2009;48(40):9492–502. doi:10.1021/bi9001248.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  138. Lee MJ, Nishio H, Ayaki H, et al. Upregulation of stress response mRNAs in COS-7 cells exposed to cadmium. Toxicology. 2002;174(2):109–17.

    Article  CAS  PubMed  Google Scholar 

  139. Misra UK, Gawdi G, Pizzo SV. Induction of mitogenic signaling in the 1LN prostate cell line on exposure to sub-micromolar concentrations of cadmium+. Cell Signal. 2003;5(11):​1059–70.

    Article  CAS  Google Scholar 

  140. IARC. IARC monographs on the evaluation of carcinogenic risk to humans. Lyon: IARC; 1993. http://monographs.iarc.fr/ENG/monographs/vol58/.iARC.

  141. Liu J, Corton C, Dix DJ, Liu Y, et al. Genetic background but not metallothionein phenotype dictates sensitivity to cadmium-induced testicular injury in mice. Toxicol Appl Pharmacol. 2001;176(1):1–9.

    Article  CAS  PubMed  Google Scholar 

  142. Joseph P, Klishis ML. Cadmium-induced cell transformation and tumorigenesis are associated with transcriptional activation of c-fos, c-jun, and c-myc proto-oncogenes: role of cellular calcium and reactive oxygen species. Toxicol Sci. 2001;61:295–303.

    Article  CAS  PubMed  Google Scholar 

  143. Watkin RD, Nawrot T, Potts RJ, et al. Mechanisms regulating the cadmium-mediated suppression of Sp1 transcription factor activity in alveolar epithelial cells. Toxicology. 2003;184(2-3):157–78.

    Article  CAS  PubMed  Google Scholar 

  144. Obara N, Imagawa S, Nakano Y, et al. Suppression of erythropoietin gene expression by cadmium depends on inhibition of HIF-1, not stimulation of GATA-2. Arch Toxicol. 2003;77(5):267–73.

    Article  CAS  PubMed  Google Scholar 

  145. Misra UK, Gawdi G, Akabani G, et al. Cadmium-induced DNA synthesis and cell proliferation in macrophages: the role of intracellular calcium and signal transduction mechanisms. Cell Signal. 2002;14(4):327–40.

    Article  CAS  PubMed  Google Scholar 

  146. Alam J, Wicks C, Stewart D, et al. Mechanism of heme oxygenase-1 gene activation by cadmium in MCF-7 mammary epithelial cells. Role of p38 kinase and Nrf2 transcription factor. J Biol Chem. 2000;275(36):27694–702.

    CAS  PubMed  Google Scholar 

  147. Joseph P, Lei YX, Whong WZ, et al. Molecular cloning and functional analysis of a novel cadmium-responsive proto-oncogene. Cancer Res. 2000;62(3):703–7.

    Google Scholar 

  148. Joseph P, Lei YX, Whong WZ, et al. Oncogenic potential of mouse translation elongation factor-1 delta, a novel cadmium-responsive proto-oncogene. J Biol Chem. 2000;277(8):6131–6.

    Article  CAS  Google Scholar 

  149. Luparello C, Sirchia R, Longo A. Cadmium as a transcriptional modulator in human cells. Crit Rev Toxicol. 2011;41(1):75–82.

    Article  PubMed  CAS  Google Scholar 

  150. Joseph P, Lei YX, Ong TM. Up-regulation of expression of translation factors—a novel molecular mechanism for cadmium carcinogenesis. Mol Cell Biochem. 2004;255(1-2):93–101.

    Article  CAS  PubMed  Google Scholar 

  151. Mukherjee JJ, Gupta SK, Kumar S, et al. Effects of cadmium(II) on (+/−)-anti-benzo[a]pyrene-7,8-diol-9,10-epoxide-induced DNA damage response in human fibroblasts and DNA repair: a possible mechanism of cadmium’s co-genotoxicity. Chem Res Toxicol. 2004;17(3):287–93.

    Article  CAS  PubMed  Google Scholar 

  152. Chao JI, Yang JL. Opposite roles of ERK and p38 mitogen-activated protein kinases in cadmium-induced genotoxicity and mitotic arrest. Chem Res Toxicol. 2001;14(9):1193–202.

    Article  CAS  PubMed  Google Scholar 

  153. Chatterjee S, Kundu S, Sengupta S, et al. Divergence to apoptosis from ROS induced cell cycle arrest: effect of cadmium. Mutat Res. 2009;663(1-2):22–31.

    Article  CAS  PubMed  Google Scholar 

  154. Choi YJ, Yin HQ, Suh HR, et al. Involvement of E2F1 transcriptional activity in cadmium-induced cell-cycle arrest at G1 in human lung fibroblasts. Environ Mol Mutagen. 2011;52(2):145–52.

    Article  CAS  PubMed  Google Scholar 

  155. Kim J, Kim SH, Johnson VJ, et al. Extracellular signal-regulated kinase-signaling-dependent G2/M arrest and cell death in murine macrophages by cadmium. Environ Toxicol Chem. 2005;24(12):3069–77.

    Article  CAS  PubMed  Google Scholar 

  156. Xie J, Shaikh ZA. Cadmium induces cell cycle arrest in rat kidney epithelial cells in G2/M phase. Toxicology. 2006;224(1-2):56–65.

    Article  CAS  PubMed  Google Scholar 

  157. Bork BU, Lee WK, Kuchler A. Cadmium-induced DNA damage triggers G (2)/M arrest via chk1/2 and cdc2 in p53-deficient kidney proximal tubule cells. Am J Physiol Renal Physiol. 2010;298(2):F255–65.

    Article  CAS  PubMed  Google Scholar 

  158. Joseph P. Mechanisms of cadmium carcinogenesis. Toxicol Appl Pharmacol. 2009;238(3):​73–9.

    Article  CAS  Google Scholar 

  159. Achanzar WE, Diwan BA, Liu J, et al. Cadmium-induced malignant transformation of human prostate epithelial cells. Cancer Res. 2001;61(2):455–8.

    CAS  PubMed  Google Scholar 

  160. Achanzar WE, Webber MM, Waalkes MP. Altered apoptotic gene expression and acquired apoptotic resistance in cadmium-transformed human prostate epithelial cells. Prostate. 2002;52(3):236–44.

    Article  CAS  PubMed  Google Scholar 

  161. Yuan C, Kadiiska M, Achanzar WE, et al. Possible role of caspase-3 inhibition in cadmium-induced blockage of apoptosis. Toxicol Appl Pharmacol. 2000;164(3):321–9.

    Article  CAS  PubMed  Google Scholar 

  162. Shimada H, Shiao YH, Shibata M, et al. Cadmium suppresses apoptosis induced by chromium. J Toxicol Environ Health. 1998;54(2):159–68.

    Article  CAS  Google Scholar 

  163. Shih YL, Lin CJ, Hsu SW, et al. Cadmium toxicity toward caspase-independent apoptosis through the mitochondria-calcium pathway in mtDNA-depleted cells. Ann N Y Acad Sci. 2005;1042:497–505.

    Article  CAS  PubMed  Google Scholar 

  164. Lee WK, Abouhamed M, Thévenod F. Caspase-dependent and -independent pathways for cadmium-induced apoptosis in cultured kidney proximal tubule cells. Am J Physiol Renal Physiol. 2006;291(4):F823–32.

    Article  CAS  PubMed  Google Scholar 

  165. Shih CM, Ko WC, Wu JS, et al. Mediating of caspase-independent apoptosis by cadmium through the mitochondria-ROS pathway in MRC-5 fibroblasts. J Cell Biochem. 2004;91(2):​384–97.

    Article  CAS  PubMed  Google Scholar 

  166. Coutant A, Lebeau J, Bidon-Wagner N, et al. Cadmium-induced apoptosis in lymphoblastoid cell line: involvement of caspase-dependent and -independent pathways. Biochimie. 2006;88(11):1815–22.

    Article  CAS  PubMed  Google Scholar 

  167. Venza M, Visalli M, Biondo C, et al. Epigenetic effects of cadmium in cancer: focus on melanoma. Curr Genomics. 2014;15(6):420–35.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  168. Zhou ZH, Lei YX, Wang CX. Analysis of aberrant methylation in DNA repair genes during malignant transformation of human bronchial epithelial cells induced by cadmium. Toxicol Sci. 2012;125(2):412–7.

    Article  CAS  PubMed  Google Scholar 

  169. Takiguchi M, Achanzar WE, Qu W, Li G, Waalkes MP. Effects of cadmium on DNA-(Cytosine-5) methyltransferase activity and DNA methylation status during cadmium-induced cellular transformation. Exp Cell Res. 2003;286(2):355–65.

    Article  CAS  PubMed  Google Scholar 

  170. Wright RO, Schwartz J, Wright RJ, et al. Biomarkers of lead exposure and DNA methylation within retrotransposons. Environ Health Perspect. 2010;118(6):790–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  171. Cho YH, Yazici H, Wu HC, Terry MB, et al. Aberrant promoter hyper-methylation and genomic hypo-methylation in tumor, adjacent normal tissues and blood from breast cancer patients. Anticancer Res. 2010;30(7):2489–96.

    CAS  PubMed  PubMed Central  Google Scholar 

  172. Choi SH, Worswick S, Byun HM. Changes in DNA methylation of tandem DNA repeats are different from interspersed repeats in cancer. Int J Cancer. 2009;125(3):723–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  173. Zhou XD, Sens MA, Garrett SH, et al. Enhanced expression of metallothionein isoform 3 (MT-3) protein in tumor hetero-transplants derived from As3+ and Cd+2 transformed human urothelial cells. Toxicol Sci. 2006;93:322–30.

    Article  CAS  PubMed  Google Scholar 

  174. Somji S, Garrett SH, Toni C, et al. Differences in the epigenetic regulation of MT-3 gene expression between parental and Cd+2 or As+3 transformed human urothelial cells. Cancer Cell Int. 2011;11(1):2.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  175. Chen P, Duan X, Li M, et al. Systematic network assessment of the carcinogenic activities of cadmium. Toxicol Appl Pharmacol. 2016;310:9150–8.

    Google Scholar 

  176. Smith MT, Guyton KZ, Gibbons CF, et al. key characteristics of carcinogens as a basis for organizing data on Mechanisms of carcinogenesis. Environ Health Perspect. 2016;124(6):713–21.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Hazardous Pollutants Assessment Group, National Center for Environmental Assessment, United States Environmental Protection Agency, Research Triangle Park, NC, 27711, USA

    Anuradha Mudipalli

Authors
  1. Anuradha Mudipalli
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Anuradha Mudipalli .

Editor information

Editors and Affiliations

  1. Natl Ctr Envtl Assessment Office of Res and Devt, Research Triangle Park, North Carolina, USA

    Anuradha Mudipalli

  2. Professor of Environmental Medicine, New York University, Tuxedo, New York, USA

    Judith T. Zelikoff

Rights and permissions

Reprints and permissions

Copyright information

© 2017 Springer International Publishing AG

About this chapter

Cite this chapter

Mudipalli, A. (2017). Cadmium Carcinogenesis and Mechanistic Insights. In: Mudipalli, A., Zelikoff, J. (eds) Essential and Non-essential Metals. Molecular and Integrative Toxicology. Humana Press, Cham. https://doi.org/10.1007/978-3-319-55448-8_6

Download citation

Publish with us

Policies and ethics

Search

Navigation