Location via proxy:   [ UP ]  
[Report a bug]   [Manage cookies]                
Skip to main content

Advertisement

Springer Nature Link
Log in

Disruption of Mitotic Progression by Arsenic

  • Published:
Biological Trace Element Research Aims and scope Submit manuscript

Abstract

Arsenic is an enigmatic xenobiotic that causes a multitude of chronic diseases including cancer and also is a therapeutic with promise in cancer treatment. Arsenic causes mitotic delay and induces aneuploidy in diploid human cells. In contrast, arsenic causes mitotic arrest followed by an apoptotic death in a multitude of virally transformed cells and cancer cells. We have explored the hypothesis that these differential effects of arsenic exposure are related by arsenic disruption of mitosis and are differentiated by the target cell’s ability to regulate or modify cell cycle checkpoints. Functional p53/CDKN1A axis has been shown to mitigate the mitotic block and to be essential to induction of aneuploidy. More recent preliminary data suggest that microRNA modulation of chromatid cohesion also may play a role in escape from mitotic block and in generation of chromosomal instability. Other recent studies suggest that arsenic may be useful in treatment of solid tumors when used in combination with other cytotoxic agents such as cisplatin.

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

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Mondal D, Banerjee M, Kundu M, Banerjee N, Bhattacharya U, Giri AK, Ganguli B, Sen Roy S, Polya DA (2010) Comparison of drinking water, raw rice and cooking of rice as arsenic exposure routes in three contrasting areas of West Bengal, India. Environ Geochem Health 32(6):463–477. doi:10.1007/s10653-010-9319-5

    Article  CAS  PubMed  Google Scholar 

  2. Polya D, Charlet L (2009) Environmental science: rising arsenic risk? Nat Geosci 2(6):383–384

    Article  CAS  Google Scholar 

  3. Yoshida T, Yamauchi H, Fan Sun G (2004) Chronic health effects in people exposed to arsenic via the drinking water: dose-response relationships in review. Toxicol Appl Pharmacol 198(3):243–252. doi:10.1016/j.taap.2003.10.022

    Article  CAS  PubMed  Google Scholar 

  4. Kapaj S, Peterson H, Liber K, Bhattacharya P (2006) Human health effects from chronic arsenic poisoning—a review. J Environ Sci Health, Part A: Tox Hazard Subst Environ Eng 41(10):2399–2428. doi:10.1080/10934520600873571

    Article  CAS  Google Scholar 

  5. Vahidnia A, van der Voet GB, de Wolff FA (2007) Arsenic neurotoxicity—a review. Hum Exp Toxicol 26(10):823–832. doi:10.1177/0960327107084539

    Article  CAS  PubMed  Google Scholar 

  6. Guha Mazumder DN (2008) Chronic arsenic toxicity & human health. Indian J Med Res 128(4):436–447

    CAS  PubMed  Google Scholar 

  7. Soto-Martinez M, Sly PD (2010) Relationship between environmental exposures in children and adult lung disease: the case for outdoor exposures. Chron Respir Dis 7(3):173–186. doi:10.1177/1479972309345929

    Article  PubMed  Google Scholar 

  8. Guha Mazumder D, Dasgupta UB (2011) Chronic arsenic toxicity: studies in West Bengal, India. Kaohsiung J Med Sci 27(9):360–370. doi:10.1016/j.kjms.2011.05.003

    Article  CAS  PubMed  Google Scholar 

  9. Liu J, Lu Y, Wu Q, Goyer RA, Waalkes MP (2008) Mineral arsenicals in traditional medicines: orpiment, realgar, and arsenolite. J Pharmacol Exp Ther 326(2):363–368. doi:10.1124/jpet.108.139543

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  10. Kennedy PG (2013) Clinical features, diagnosis, and treatment of human African trypanosomiasis (sleeping sickness). Lancet Neurol 12(2):186–194. doi:10.1016/S1474-4422(12)70296-X

    Article  PubMed  Google Scholar 

  11. Antman KH (2001) Introduction: the history of arsenic trioxide in cancer therapy. Oncologist 6(Suppl 2):1–2

    Article  CAS  PubMed  Google Scholar 

  12. Humans. IWGotEoCRt (2012) Arsenic, metals, fibres, and dusts. IARC Monogr Eval Carcinog Risks Hum 100(Pt C):11–465

    Google Scholar 

  13. Waalkes MP, Liu J, Diwan BA (2007) Transplacental arsenic carcinogenesis in mice. Toxicol Appl Pharmacol 222(3):271–280. doi:10.1016/j.taap.2006.12.034

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  14. Tokar EJ, Diwan BA, Ward JM, Delker DA, Waalkes MP (2011) Carcinogenic effects of “whole-life” exposure to inorganic arsenic in CD1 mice. Toxicol Sci 119(1):73–83. doi:10.1093/toxsci/kfq315

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  15. Subcommittee on Arsenic in Drinking Water, National Research Council (1999) Arsenic in drinking water. National Academy Press, Washington

  16. Subcommittee to Update the 1999 Arsenic in Drinking Water Report, Committee on Toxicology, Board on Environmental Studies and Toxicology, National Research Council (2001) Arsenic in drinking water: 2001 update. National Academy Press, Washington

  17. Cassidy LD, Liau SS, Venkitaraman AR (2014) Chromosome instability and carcinogenesis: insights from murine models of human pancreatic cancer associated with BRCA2 inactivation. Mol Oncol 8(2):161–168. doi:10.1016/j.molonc.2013.10.005

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  18. Wu Y, Antony S, Meitzler JL, Doroshow JH (2014) Molecular mechanisms underlying chronic inflammation-associated cancers. Cancer Lett 345(2):164–173. doi:10.1016/j.canlet.2013.08.014

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  19. Kops GJPL, Weaver BAA, Cleveland DW (2005) On the road to cancer: aneuploidy and the mitotic checkpoint. Nat Rev Cancer 5(10):773–785

    Article  CAS  PubMed  Google Scholar 

  20. Shen ZX, Chen GQ, Ni JH, Li XS, Xiong SM, Qiu QY, Zhu J, Tang W, Sun GL, Yang KQ, Chen Y, Zhou L, Fang ZW, Wang YT, Ma J, Zhang P, Zhang TD, Chen SJ, Chen Z, Wang ZY (1997) Use of arsenic trioxide (As2O3) in the treatment of acute promyelocytic leukemia (APL): II. Clinical efficacy and pharmacokinetics in relapsed patients. Blood 89(9):3354–3360

    CAS  PubMed  Google Scholar 

  21. Iland HJ, Seymour JF (2013) Role of arsenic trioxide in acute promyelocytic leukemia. Curr Treat Options Oncol 14(2):170–184. doi:10.1007/s11864-012-0223-3

    Article  PubMed  Google Scholar 

  22. Lo-Coco F, Avvisati G, Vignetti M, Thiede C, Orlando SM, Iacobelli S, Ferrara F, Fazi P, Cicconi L, Di BE, Specchia G, Sica S, Divona M, Levis A, Fiedler W, Cerqui E, Breccia M, Fioritoni G, Salih HR, Cazzola M, Melillo L, Carella AM, Brandts CH, Morra E, von Lilienfeld-Toal M, Hertenstein B, Wattad M, Lubbert M, Hanel M, Schmitz N, Link H, Kropp MG, Rambaldi A, La NG, Luppi M, Ciceri F, Finizio O, Venditti A, Fabbiano F, Dohner K, Sauer M, Ganser A, Amadori S, Mandelli F, Dohner H, Ehninger G, Schlenk RF, Platzbecker U (2013) Retinoic acid and arsenic trioxide for acute promyelocytic leukemia. N Engl J Med 369(2):111–121. doi:10.1056/NEJMoa1300874

    Article  CAS  PubMed  Google Scholar 

  23. Zhang XW, Yan XJ, Zhou ZR, Yang FF, Wu ZY, Sun HB, Liang WX, Song AX, Lallemand-Breitenbach V, Jeanne M, Zhang QY, Yang HY, Huang QH, Zhou GB, Tong JH, Zhang Y, Wu JH, Hu HY, de Thé H, Chen SJ, Chen Z (2010) Arsenic trioxide controls the fate of the PML-RARalpha oncoprotein by directly binding PML. Science 328(5975):240–243. doi:10.1126/science.1183424

    Article  CAS  PubMed  Google Scholar 

  24. Ramirez-Solis A, Mukopadhyay R, Rosen BP, Stemmler TL (2004) Experimental and theoretical characterization of arsenite in water: insights into the coordination environment of As-O. Inorg Chem 43(9):2954–2959. doi:10.1021/ic0351592

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  25. McNeely SC, Taylor BF, States JC (2008) Mitotic arrest-associated apoptosis induced by sodium arsenite in A375 melanoma cells is BUBR1-dependent. Toxicol Appl Pharmacol 231(1):61–67. doi:10.1016/j.taap.2008.03.020

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  26. Qu GP, Xiu QY, Li B, Liu YA, Zhang LZ (2009) Arsenic trioxide inhibits the growth of human lung cancer cell lines via cell cycle arrest and induction of apoptosis at both normoxia and hypoxia. Toxicol Ind Health 25(8):505–515. doi:10.1177/0748233709345936

    Article  CAS  PubMed  Google Scholar 

  27. Akao Y, Yamada H, Nakagawa Y (2000) Arsenic-induced apoptosis in malignant cells in vitro. Leuk Lymphoma 37(1–2):53–63. doi:10.3109/10428190009057628

    Article  CAS  PubMed  Google Scholar 

  28. Kong B, Huang S, Wang W, Ma D, Qu X, Jiang J, Yang X, Zhang Y, Wang B, Cui B, Yang Q (2005) Arsenic trioxide induces apoptosis in cisplatin-sensitive and -resistant ovarian cancer cell lines. IntJ Gynecol Cancer 15(5):872–877. doi:10.1111/j.1525-1438.2005.00251.x

    Article  CAS  Google Scholar 

  29. Uslu R, Sanli UA, Sezgin C, Karabulut B, Terzioglu E, Omay SB, Goker E (2000) Arsenic trioxide-mediated cytotoxicity and apoptosis in prostate and ovarian carcinoma cell lines. Clin Cancer Res 6(12):4957–4964

    CAS  PubMed  Google Scholar 

  30. Pu YS, Hour TC, Chen J, Huang CY, Guan JY, Lu SH (2002) Arsenic trioxide as a novel anticancer agent against human transitional carcinoma—characterizing its apoptotic pathway. Anti-Cancer Drugs 13(3):293–300

    Article  CAS  PubMed  Google Scholar 

  31. Yih LH, Ho IC, Lee TC (1997) Sodium arsenite disturbs mitosis and induces chromosome loss in human fibroblasts. Cancer Res 57(22):5051–5059

    CAS  PubMed  Google Scholar 

  32. Porter PC, Clark DR, McDaniel LD, McGregor WG, States JC (2006) Telomerase-immortalized human fibroblasts retain UV-induced mutagenesis and p53-mediated DNA damage responses. DNA Repair 5(1):61–70. doi:10.1016/j.dnarep.2005.07.005

    Article  CAS  PubMed  Google Scholar 

  33. States JC, Reiners JJ Jr, Pounds JG, Kaplan DJ, Beauerle BD, McNeely SC, Mathieu P, McCabe MJ Jr (2002) Arsenite disrupts mitosis and induces apoptosis in SV40-transformed human skin fibroblasts. Toxicol Appl Pharmacol 180(2):83–91. doi:10.1006/taap.2002.9376

    Article  CAS  PubMed  Google Scholar 

  34. Vega L, Gonsebatt ME, Ostrosky-Wegman P (1995) Aneugenic effect of sodium arsenite on human lymphocytes in vitro: an individual susceptibility effect detected. Mutat Res 334(3):365–373. doi:10.1016/0165-1161(95)90074-8

    Article  CAS  PubMed  Google Scholar 

  35. Salazar AM, Miller HL, McNeely SC, Sordo M, Ostrosky-Wegman P, States JC (2010) Suppression of p53 and p21CIP1/WAF1 reduces arsenite-induced aneuploidy. Chem Res Toxicol 23(2):357–364. doi:10.1021/tx900353v

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  36. McNeely SC, Xu X, Taylor BF, Zacharias W, McCabe MJ Jr, States JC (2006) Exit from arsenite-induced mitotic arrest is p53 dependent. Environ Health Perspect 114(9):1401–1406

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  37. Taylor BF, McNeely SC, Miller HL, Lehmann GM, McCabe MJ, States JC (2006) p53 suppression of arsenite-induced mitotic catastrophe is mediated by p21CIP1/WAF1. J Pharmacol Exp Ther 318(1):142–151. doi:10.1124/jpet.106.103077

    Article  CAS  PubMed  Google Scholar 

  38. Ghosh P, Basu A, Singh KK, Giri AK (2008) Evaluation of cell types for assessment of cytogenetic damage in arsenic exposed population. Mol Cancer 7:45. doi:10.1186/1476-4598-7-45

    Article  PubMed Central  PubMed  Google Scholar 

  39. 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(5):820–827

    CAS  Google Scholar 

  40. Basu A, Mahata J, Roy AK, Sarkar JN, Poddar G, Nandy AK, Sarkar PK, Dutta PK, Banerjee A, Das M, Ray K, Roychaudhury S, Natarajan AT, Nilsson R, Giri AK (2002) Enhanced frequency of micronuclei in individuals exposed to arsenic through drinking water in West Bengal, India. Mutat Res 516(1–2):29–40

    Article  CAS  PubMed  Google Scholar 

  41. Ghosh P, Basu A, Mahata J, Basu S, Sengupta M, Das JK, Mukherjee A, Sarkar AK, Mondal L, Ray K, Giri AK (2006) Cytogenetic damage and genetic variants in the individuals susceptible to arsenic-induced cancer through drinking water. Int J Cancer 118(10):2470–2478. doi:10.1002/ijc.21640

    Article  CAS  PubMed  Google Scholar 

  42. Gonsebatt ME, Vega L, Salazar AM, Montero R, Guzman P, Blas J, Del Razo LM, Garcia-Vargas G, Albores A, Cebrian ME, Kelsh M, Ostrosky-Wegman P (1997) Cytogenetic effects in human exposure to arsenic. Mutat Res 386(3):219–228

    Article  CAS  PubMed  Google Scholar 

  43. Ling YH, Jiang JD, Holland JF, Perez-Soler R (2002) Arsenic trioxide produces polymerization of microtubules and mitotic arrest before apoptosis in human tumor cell lines. Mol Pharmacol 62(3):529–538

    Article  CAS  PubMed  Google Scholar 

  44. McNeely SC, Belshoff AC, Taylor BF, Fan TW, McCabe MJ Jr, Pinhas AR, States JC (2008) Sensitivity to sodium arsenite in human melanoma cells depends upon susceptibility to arsenite-induced mitotic arrest. Toxicol Appl Pharmacol 229(2):252–261. doi:10.1016/j.taap.2008.01.020

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  45. Wu YC, Yen WY, Yih LH (2008) Requirement of a functional spindle checkpoint for arsenite-induced apoptosis. J Cell Biochem 105(3):678–687. doi:10.1002/jcb.21861

    Article  CAS  PubMed  Google Scholar 

  46. Yih LH, Wu YC, Hsu NC, Kuo HH (2012) Arsenic trioxide induces abnormal mitotic spindles through a PIP4KIIgamma/Rho pathway. Toxicol Sci 128(1):115–125. doi:10.1093/toxsci/kfs129

    Article  CAS  PubMed  Google Scholar 

  47. Yih LH, Hsueh SW, Luu WS, Chiu TH, Lee TC (2005) Arsenite induces prominent mitotic arrest via inhibition of G2 checkpoint activation in CGL-2 cells. Carcinogenesis 26(1):53–63. doi:10.1093/carcin/bgh295

    Article  CAS  PubMed  Google Scholar 

  48. Yih LH, Tseng YY, Wu YC, Lee TC (2006) Induction of centrosome amplification during arsenite-induced mitotic arrest in CGL-2 cells. Cancer Res 66(4):2098–2106. doi:10.1158/0008-5472.CAN-05-2308

    Article  CAS  PubMed  Google Scholar 

  49. Taylor BF, McNeely SC, Miller HL, States JC (2008) Arsenite-induced mitotic death involves stress response and is independent of tubulin polymerization. Toxicol Appl Pharmacol 230(2):235–246. doi:10.1016/j.taap.2008.02.030

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  50. Wu YC, Yen WY, Lee TC, Yih LH (2009) Heat shock protein inhibitors, 17-DMAG and KNK437, enhance arsenic trioxide-induced mitotic apoptosis. Toxicol Appl Pharmacol 236(2):231–238. doi:10.1016/j.taap.2009.02.003

    Article  CAS  PubMed  Google Scholar 

  51. Helm CW, States JC (2009) Enhancing the efficacy of cisplatin in ovarian cancer treatment—could arsenic have a role. J Ovarian Res 2:2. doi:10.1186/1757-2215-2-2

    Article  PubMed Central  PubMed  Google Scholar 

  52. Nakaoka T, Ota A, Ono T, Karnan S, Konishi H, Furuhashi A, Ohmura Y, Yamada Y, Hosokawa Y, Kazaoka Y (2014) Combined arsenic trioxide-cisplatin treatment enhances apoptosis in oral squamous cell carcinoma cells. Cell Oncol (Dordr) 37(2):119–129. doi:10.1007/s13402-014-0167-7

    Article  CAS  Google Scholar 

  53. Byun JM, Jeong DH, Lee DS, Kim JR, Park SG, Kang MS, Kim YN, Lee KB, Sung MS, Kim KT (2013) Tetraarsenic oxide and cisplatin induce apoptotic synergism in cervical cancer. Oncol Rep 29(4):1540–1546. doi:10.3892/or.2013.2243

    CAS  PubMed  Google Scholar 

  54. Kotowski U, Heiduschka G, Brunner M, Erovic BM, Martinek H, Thurnher D (2012) Arsenic trioxide enhances the cytotoxic effect of cisplatin in head and neck squamous cell carcinoma cell lines. Oncol Lett 3(6):1326–1330. doi:10.3892/ol.2012.643

    CAS  PubMed Central  PubMed  Google Scholar 

  55. Zhang N, Wu ZM, McGowan E, Shi J, Hong ZB, Ding CW, Xia P, Di W (2009) Arsenic trioxide and cisplatin synergism increase cytotoxicity in human ovarian cancer cells: therapeutic potential for ovarian cancer. Cancer Sci 100(12):2459–2464. doi:10.1111/j.1349-7006.2009.01340.x

    Article  CAS  PubMed  Google Scholar 

  56. Li H, Zhu X, Zhang Y, Xiang J, Chen H (2009) Arsenic trioxide exerts synergistic effects with cisplatin on non-small cell lung cancer cells via apoptosis induction. J ExpClin Cancer Res 28:110. doi:10.1186/1756-9966-28-110

    Google Scholar 

  57. Muenyi CS, Pinhas AR, Fan TW, Brock GN, Helm CW, States JC (2012) Sodium arsenite +/- hyperthermia sensitizes p53-expressing human ovarian cancer cells to cisplatin by modulating platinum-DNA damage responses. Toxicol Sci 127(1):139–149. doi:10.1093/toxsci/kfs085

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  58. Muenyi CS, States VA, Masters JH, Fan TW, Helm CW, States JC (2011) Sodium arsenite and hyperthermia modulate cisplatin-DNA damage responses and enhance platinum accumulation in murine metastatic ovarian cancer xenograft after hyperthermic intraperitoneal chemotherapy (HIPEC). J Ovarian Res 4:9. doi:10.1186/1757-2215-4-9

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  59. Muenyi CS, Trivedi AP, Helm CW, States JC (2014) Cisplatin plus sodium arsenite and hyperthermia induces pseudo-G1 associated apoptotic cell death in ovarian cancer cells. Toxicol Sci 139(1):74–82. doi:10.1093/toxsci/kfu029

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  60. Stevens JB, Abdallah BY, Liu G, Ye CJ, Horne SD, Wang G, Savasan S, Shekhar M, Krawetz SA, Huttemann M, Tainsky MA, Wu GS, Xie Y, Zhang K, Heng HH (2011) Diverse system stresses: common mechanisms of chromosome fragmentation. Cell Death Dis 2:e178. doi:10.1038/cddis.2011.60

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  61. Stevens JB, Abdallah BY, Regan SM, Liu G, Bremer SW, Ye CJ, Heng HH (2010) Comparison of mitotic cell death by chromosome fragmentation to premature chromosome condensation. Mol Cytogenet 3:20. doi:10.1186/1755-8166-3-20

    Article  PubMed Central  PubMed  Google Scholar 

  62. Stevens JB, Liu G, Bremer SW, Ye KJ, Xu W, Xu J, Sun Y, Wu GS, Savasan S, Krawetz SA, Ye CJ, Heng HH (2007) Mitotic cell death by chromosome fragmentation. Cancer Res 67(16):7686–7694. doi:10.1158/0008-5472.CAN-07-0472

    Article  CAS  PubMed  Google Scholar 

  63. Liu G, Stevens JB, Horne SD, Abdallah BY, Ye KJ, Bremer SW, Ye CJ, Chen DJ, Heng HH (2014) Genome chaos: survival strategy during crisis. Cell Cycle 13(4):528–537. doi:10.4161/cc.27378

    Article  CAS  PubMed  Google Scholar 

  64. Peters JM (2002) The anaphase-promoting complex: proteolysis in mitosis and beyond. Mol Cell 9(5):931–943

    Article  CAS  PubMed  Google Scholar 

  65. Uhlmann F (2001) Secured cutting: controlling separase at the metaphase to anaphase transition. EMBO Rep 2(6):487–492. doi:10.1093/embo-reports/kve113

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  66. Li H, Yin C, Zhang B, Sun Y, Shi L, Liu N, Liang S, Lu S, Liu Y, Zhang J, Li F, Li W, Liu F, Sun L, Qi Y (2013) PTTG1 promotes migration and invasion of human non-small cell lung cancer cells and is modulated by miR-186. Carcinogenesis 34(9):2145–2155. doi:10.1093/carcin/bgt158

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

The author is indebted to the students and collaborators who contributed to the work discussed in this review. In no particular order, these include Sam McNeely, Frazier Taylor, Ana Maria Salazar, Ashok Giri, Vanessa States, Heather Miller, Clarisse Muenyi, Josh Masters, and Patricia Ostroskey-Wegman. The work discussed was supported in part by USPHS grant ES011314.

Author information

Authors and Affiliations

  1. Department of Pharmacology and Toxicology, University of Louisville, 505 S. Hancock St, Louisville, KY, 40202, USA

    J. Christopher States

Authors
  1. J. Christopher States
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to J. Christopher States.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

States, J.C. Disruption of Mitotic Progression by Arsenic. Biol Trace Elem Res 166, 34–40 (2015). https://doi.org/10.1007/s12011-015-0306-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12011-015-0306-7

Keywords