Skip to main content

Advertisement

SpringerLink
Log in

Abnormal Blood Levels of Trace Elements and Metals, DNA Damage, and Breast Cancer in the State of Kuwait

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

Abstract

This study aims at investigating the blood level of Cu, Zn, Se, and Cd in breast cancer patients and the association between such level and the frequency of micronucleated lymphocytes. Fifty stage I breast cancer patients were recruited for this study at the time of diagnosis and before receiving any treatment or surgery. The control group consisted of 150 normal females matched to the patients for age (± 5 years). The whole blood level of Cu, Zn, Se, and Cd was determined using spectrophotometry. The frequency of micronucleated lymphocytes in the blood was determined using the cytokinesis-block micronucleus assay. The level of Cu, Zn, and Se was significantly lower (p = 0.0006, <0.0001, and <0.0001, respectively) in breast cancer patients, as compared to controls. The level of Cd was significantly (p < 0.0001) higher in the patients, as compared to controls. The frequency of lymphocytes with one micronucleus was significantly (p < 0.0001) higher in the patients, as compared to controls. In breast cancer patients, the frequency of micronucleated lymphocytes showed different associations with different levels of these trace elements. High Cd, low Zn, low Se, and both high and low Cu levels were significantly associated with micronucleus formation in lymphocytes. A similar association was found in the normal control group only in relation to high Se and Cd levels. Breast cancer patients seem to have abnormal levels of Cu, Zn, Se, and Cd, and such abnormality is associated with micronucleus formation in lymphocytes.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Durakovic A (2003) Undiagnosed illnesses and radioactive warfare. Croat Med J 44:520–532

    PubMed  Google Scholar 

  2. El-basmy AA, Al-asfour A (2005) Kuwait Cancer Registry annual report

  3. Rosenzweig AC, Sazinsky MH (2006) Structural insights into dioxygen-activating copper enzymes. Curr Opin Struc Biol 16:729–735

    Article  CAS  Google Scholar 

  4. Ridge PG, Zhang Y, Gladyshev VN (2008) Comparative genomic analyses of copper transporters and cuproproteomes reveal evolutionary dynamics of copper utilization and its link to oxygen. PLoS One 3:e1378

    Article  PubMed  Google Scholar 

  5. Matoba S, Kang JG, Patino WD, Wragg A, Boehm M et al (2006) p53 regulates mitochondrial respiration. Science 312:1650–1653

    Article  PubMed  CAS  Google Scholar 

  6. Payne SL, Hendrix MJ, Kirschmann DA (2007) Paradoxical roles for lysyl oxidases in cancer—a prospect. J Cell Biochem 101:1338–1354

    Article  PubMed  CAS  Google Scholar 

  7. Singh V, Garg AN (1998) Trace element correlations in the blood of Indian women with breast cancer. Biol Trace Element Res 64:237–245

    Article  CAS  Google Scholar 

  8. Ip C (1986) The chemopreventive role of selenium in carcinogenesis. Adv Exp Med Biol 206:431–447

    PubMed  CAS  Google Scholar 

  9. Hu G, Han C, Wild CP, Hall J, Chen J (1992) Lack of effects of selenium on N-nitrosomethylbenzylamine-induced tumorigenesis, DNA methylation, and oncogene expression in rats and mice. Nutr Cancer 18:287–295

    Article  PubMed  CAS  Google Scholar 

  10. Schrauzer GN (2006) Interactive effects of selenium and chromium on mammary tumor development and growth in MMTV-infected female mice and their relevance to human cancer. Biol Trace Elem Res 109:281–292

    Article  PubMed  CAS  Google Scholar 

  11. Schrauzer GN (2008) Interactive effects of selenium and cadmium on mammary tumor development and growth in MMTV-infected female mice. A model study on the roles of cadmium and selenium in human breast cancer. Biol Trace Elem Res 123:27–34

    Article  PubMed  CAS  Google Scholar 

  12. Schrauzer GN (2008) Effects of selenium and low levels of lead on mammary tumor development and growth in MMTV-infected female mice. Biol Trace Elem Res 125:268–275

    Article  PubMed  CAS  Google Scholar 

  13. Lou J, He J, Zheng W, Jin L, Chen Z et al (2007) Investigating the genetic instability in the peripheral lymphocytes of 36 untreated lung cancer patients with comet assay and micronucleus assay. Mutat Res 617:104–110

    PubMed  CAS  Google Scholar 

  14. Jacobson-kram D, Contrera JF (2007) Genetic toxicity assessment: employing the best science for human safety evaluation. Part I: early screening for potential human mutagens. Toxicol Sci 96:16–20

    Article  PubMed  CAS  Google Scholar 

  15. Lin Y, Keane M, Ensell M (2005) In vitro genotoxicity of exhaust emissions of diesel and gasoline engine vehicle on a united driving cycle. J Environ Monit 7:60–66

    Article  Google Scholar 

  16. Mcdiarmid MA, Engelhardt SM, Oliver M, Gucer P, Wilson PD et al (2007) Health surveillance of Gulf War I veterans exposed to depleted uranium: updating the cohort. Health Phys 93:60–73

    Article  PubMed  CAS  Google Scholar 

  17. Kodama Y, Pawel D, Nakamura N, Preston D, Honda T et al (2001) Stable chromosome aberrations in atomic bomb survivors: results from 25 years of investigation. Radiat Res 156:337–346

    Article  PubMed  CAS  Google Scholar 

  18. Heuser VD, Erdtmann B, Kvitko K, Rohr P, Da Silva J (2007) Evaluation of genetic damage in Brazilian footwear-workers: biomarkers of exposure, effect, and susceptibility. Toxicology 232:235–247

    Article  PubMed  CAS  Google Scholar 

  19. Albertini RJ (2004) Mechanistic insights from biomarker studies: somatic mutations and rodent/human comparisons following exposure to a potential carcinogen. IARC Sci Publ 157:153–177

    PubMed  Google Scholar 

  20. Montero R, Serrano L, Davila V, Segura Y, Arrieta A et al (2003) Metabolic polymorphisms and the micronucleus frequency in buccal epithelium of adolescents living in an urban environment. Environ Mol Mutagen 42:216–222

    Article  PubMed  CAS  Google Scholar 

  21. Van Delft JH, Steenwinkel MS, Van Asten JG, De Vogel N, Bruijntjes-rozier TC et al (2001) Biological monitoring the exposure to polycyclic aromatic hydrocarbons of coke oven workers in relation to smoking and genetic polymorphisms for GSTM1 and GSTT1. Ann Occup Hyg 45:395–408

    PubMed  Google Scholar 

  22. Lucero L, Pastor S, Suarez S, Durban R, Gomez C et al (2000) Cytogenetic biomonitoring of Spanish greenhouse workers exposed to pesticides: micronuclei analysis in peripheral blood lymphocytes and buccal epithelial cells. Mutat Res 464:255–262

    PubMed  CAS  Google Scholar 

  23. Van Poppel G, Verhagen H, Van’t Veer P, Van Bladeren PJ (1993) Markers for cytogenetic damage in smokers: associations with plasma antioxidants and glutathione S-transferase mu. Cancer Epidemiol Biomarkers Prev 2:441–447

    PubMed  Google Scholar 

  24. Fenech M, Bonassi S, Turner J, Lando C, Ceppi M et al (2003) Intra- and interlaboratory variation in the scoring of micronuclei and nucleoplasmic bridges in binucleated human lymphocytes. Results of an international slide-scoring exercise by the HUMN project. Mutat Res 534:45–64

    PubMed  CAS  Google Scholar 

  25. Fenech M, Holland N, Chang WP, Zeiger E, Bonassi S (1999) The Human MicroNucleus Project—an international collaborative study on the use of the micronucleus technique for measuring DNA damage in humans. Mutat Res 428:271–283

    PubMed  CAS  Google Scholar 

  26. Fenech M, Crott J, Turner J, Brown S (1999) Necrosis, apoptosis, cytostasis and DNA damage in human lymphocytes measured simultaneously within the cytokinesis-block micronucleus assay: description of the method and results for hydrogen peroxide. Mutagenesis 14:605–612

    Article  PubMed  CAS  Google Scholar 

  27. Bonassi S, Znaor A, Ceppi M, Lando C, Chang WP et al (2007) An increased micronucleus frequency in peripheral blood lymphocytes predicts the risk of cancer in humans. Carcinogenesis 28:625–631

    Article  PubMed  CAS  Google Scholar 

  28. Balasubramaniyan N, Subramanian S, Sekar N, Bhuvarahamurthy V, Govindasamy S (1994) Involvement of plasma copper, zinc and cadmium in human carcinoma of uterine cervix. Med Sci Res 22:475–476

    Google Scholar 

  29. Kuo HW, Chen SF, Wu CC, Chen DR, Lee JH (2002) Serum and tissue trace elements in patients with breast cancer in Taiwan. Biol Trace Elem Res 89:1–11

    Article  PubMed  CAS  Google Scholar 

  30. Centre for Disease Control (2005) Third national report on human exposure to environmental chemicals. Centre for Disease Control, Atlanta

    Google Scholar 

  31. Melton LA, Tracy ML, Moller G (1990) Screening trace elements and electrolytes in serum by inductively-coupled plasma emission spectrometry. Clin Chem 36:247–250

    PubMed  CAS  Google Scholar 

  32. Fenech M (2006) Cytokinesis-block micronucleus assay evolves into a “cytome” assay of chromosomal instability, mitotic dysfunction and cell death. Mutat Res 600:58–66

    PubMed  CAS  Google Scholar 

  33. Fenech M, Morley AA (1985) Measurement of micronuclei in lymphocytes. Mutat Res 147:29–36

    PubMed  CAS  Google Scholar 

  34. Fenech M (2000) The in vitro micronucleus technique. Mutat Res 455:81–95

    PubMed  CAS  Google Scholar 

  35. Zhang MB, He JL, Jin LF, Lu DQ (2002) Study of low-intensity 2450-MHz microwave exposure enhancing the genotoxic effects of mitomycin C using micronucleus test and comet assay in vitro. Biomed Environ Sci 15:283–290

    PubMed  Google Scholar 

  36. Meyer F, Verreault R (1987) Erythrocyte selenium and breast cancer risk. Am J Epidemiol 125:917–919

    PubMed  CAS  Google Scholar 

  37. Huang YL, Sheu JH, Lin T-H (1999) Association between oxidative stress and changes of trace elements in patients with breast cancer. Clin Biochem 32:131–136

    Article  PubMed  CAS  Google Scholar 

  38. Sharma K, Mittal DK, Kesarwani RC, Kamboj VP (1994) Diagnostic and prognostic significance of serum and tissue trace elements in breast malignancy. Ind J Med Sci 48:227–232

    CAS  Google Scholar 

  39. Fuchs AG, Mariotto R, De Lustig ES (1986) Serum and tissue copper content in two mammary adenocarcinomas with different biological behaviour. Eur J Cancer Clin Oncol 22:1347–1352

    Article  PubMed  CAS  Google Scholar 

  40. Linder MC, Moor JR, Wright K (1981) Ceruloplasmin assays in diagnosis and treatment of human lung, breast, and gastrointestinal cancers. J Nat Cancer Instit 67:263–275

    CAS  Google Scholar 

  41. Scanni A, Licciardello L, Trovato M, Tomirotii M, Biraghi M (1977) Serum copper and ceruloplasmin levels in patients with neoplasias localized in the stomach, large intestine or lung. Tumori 63:175–180

    PubMed  CAS  Google Scholar 

  42. Chan A, Wong F, Arumanayagam M (1993) Serum ultrafiltrable copper, total copper and ceruloplasmin concentrations in gynecological carcinoma. Ann Clin Biochem 30:545–549

    PubMed  Google Scholar 

  43. Zuo XL, Chen JM, Zhou X, Li XZ, Mei GY (2006) Levels of selenium, zinc, copper and antioxidant enzyme activity in patients with leukemia. Biol Trace Elem Res 114:41–54

    Article  PubMed  CAS  Google Scholar 

  44. Sattar N, Scott HR, Mcmillan DC, Talwar D, O’Reilly DSJ (1997) Acute-phase reactants and plasma trace element concentrations in non-small cell lung cancer patients and controls. Nutr Cancer 28:308–312

    Article  PubMed  CAS  Google Scholar 

  45. Fernandez-Banares F, Cabre E, Esteve M (2002) Serum selenium and risk of large size colorectal adenomas in a geographical area with a low selenium status. Am J Gastroenterol 97:2103–2108

    PubMed  CAS  Google Scholar 

  46. Leitzmann MF, Stampfer MJ, Wu K, Colditz GA, Willett WC (2003) Zinc supplement use and risk of prostate cancer. J Natl Cancer Inst 95:1004–1007

    Article  PubMed  CAS  Google Scholar 

  47. Schrauzer GN, Molenaar T, Mead S, Kuehn K, Yamamoto H (1985) Selenium in the blood of Japanese and American women with and without breast cancer and fibrocystic disease. Jpn J Cancer Res 76:374–377

    PubMed  CAS  Google Scholar 

  48. Ghadirian P, Maisonneuve P, Perret C (2000) A case control study of toenail selenium and cancer of the breast, colon, and prostate. Cancer Detection Prev 24:305–313

    CAS  Google Scholar 

  49. Van Den Brandt PA, Zeegers MPA, Bode P, Goldbohm RA (2003) Toenail selenium levels and the subsequent risk of prostate cancer: a prospective cohort study. Cancer Epidemiol Biomark Prev 12:866–887

    Google Scholar 

  50. Mark SD, Qiao YL, Dawsey SM (2000) Prospective study of serum selenium levels and incident esophageal and gastric cancers. J Natl Cancer Inst 92:1753–1763

    Article  PubMed  CAS  Google Scholar 

  51. Helzlsouer KJ, Comstock GW, Morris JS (1989) Selenium, lycopene, alpha-tocopherol, beta-carotene, retinol, and subsequent bladder cancer. Cancer Res 49:6144–6148

    PubMed  CAS  Google Scholar 

  52. Zeegers MP, Goldbohm A, Bode P, Van Den Brandt PA (2002) Prediagnostic toenail selenium and risk of bladder cancer. Cancer Epidemiol Biomark Prev 11:1292–1297

    CAS  Google Scholar 

  53. Nomura AMY, Lee J, Stemmermann GN, Combs GF Jr (2000) Serum selenium and subsequent risk of prostate cancer. Cancer Epidemiol Biomark Prev 9:883–887

    CAS  Google Scholar 

  54. Van’t Veer P, Van Der Wielen RP, Kok F, Hermus RJ, Sturmans F (1990) Selenium in diet, blood and toenails in relation to breast cancer: a case–control study. Am J Epidemiol 131:987–994

    Google Scholar 

  55. Platz EA, Helzlsouer KJ, Hoffman SC, Morris JS, Baskett CK (2002) Prediagnostic toenail cadmium and zinc and subsequent prostate cancer risk. Prostate 52:288–296

    Article  PubMed  CAS  Google Scholar 

  56. Willett WC, Polk BF, Morris JS (1983) Prediagnostic serum selenium and risk of cancer. Lancet 2:130–134

    Article  PubMed  CAS  Google Scholar 

  57. Mcelroy JA, Shafer MM, Trentham-Dietz A, Hampton JM, Newcomb PA (2006) Cadmium exposure and breast cancer risk. J Natl Cancer Inst 98:869–873

    Article  PubMed  CAS  Google Scholar 

  58. Nagata C, Nagao Y, Shibuya C, Kashiki Y, Shimizu H (2005) Urinary cadmium and serum levels of estrogens and androgens in postmenopausal Japanese women. Cancer Epidemiol Biomarkers Prev 14:705–708

    Article  PubMed  CAS  Google Scholar 

  59. Lemen RA, Lee JS, Wagoner JK, Blejer HP (1976) Cancer mortality among cadmium production workers. Ann NY Acad Sci 271:273–279

    Article  PubMed  CAS  Google Scholar 

  60. West DW, Slattery ML, Robison LM, French TK, Mahoney AW (1991) Adult dietary intake and prostate cancer risk in Utah: a case–control study with special emphasis on aggressive tumors. Cancer Causes Control 2:85–94

    Article  PubMed  CAS  Google Scholar 

  61. Elinder CG, Kjellstrom T, Hogstedt C, Andersson K, Spang G (1985) Cancer mortality of cadmium workers. Br J Ind Med 42:651–655

    PubMed  CAS  Google Scholar 

  62. Sorahan T (1987) Mortality from lung cancer among a cohort of nickel cadmium battery workers: 1946–84. Br J Ind Med 44:803–809

    PubMed  CAS  Google Scholar 

  63. Norppa H (2004) Cytogenetic biomarkers and genetic polymorphisms. Toxicol Lett 149:309–334

    Article  PubMed  CAS  Google Scholar 

  64. Collins AR (1998) Molecular epidemiology in cancer research. Mol Aspects Med 19:359–432

    Article  PubMed  CAS  Google Scholar 

  65. Albertini RJ, Anderson D, Douglas GR, Hagmar L, Hemminki K (2000) IPCS guidelines for the monitoring of genotoxic effects of carcinogens in humans. Mutat Res 463:111–172

    Article  PubMed  CAS  Google Scholar 

  66. Savage JRK (1993) Update on target theory as applied to chromosomal aberrations. Env Mol Mutagen 22:198–207

    Article  CAS  Google Scholar 

  67. Evans HJ (1990) Cytogenetics overview. Prog Clin Biol Res 340B:301–323

    PubMed  CAS  Google Scholar 

  68. Dellarco VL, Mavournin KH, Tice RR (1985) Aneuploidy and health risk assessment: current status and future directions. Environ Mutagen 7:405–424

    Article  PubMed  CAS  Google Scholar 

  69. Guttenbach M, Schmid M (1994) Exclusion of specific human chromosomes into micronuclei by 5-azacytidine treatment of lymphocyte cultures. Exp Cell Res 21:127–132

    Article  Google Scholar 

  70. Fenech M (2007) Cytokinesis-block micronucleus cytome assay. Nat Protoc 2:1084–1104

    Article  PubMed  CAS  Google Scholar 

  71. Boffetta P, Van Der Hel O, Norppa H, Fabianova E, Fucic A (2007) Chromosomal aberrations and cancer risk: results of a cohort study from central Europe. Am J Epidemiol 165:36–43

    Article  PubMed  Google Scholar 

  72. Kops GJ, Weaver BA, Cleveland DW (2005) On the road to cancer: aneuploidy and the mitotic checkpoint. Nat Rev Cancer 5:773–785

    Article  PubMed  CAS  Google Scholar 

  73. Poli G, Biasi F, Chiarpotto E (2004) Oxidative stress and cell signaling. Curr Med Chem 11:1163–1182

    PubMed  CAS  Google Scholar 

  74. Chandra J, Samali A, Orrenius S (2000) Triggering and modulation of apoptosis by oxidative stress. Free Rad Med Biol 29:323–333

    Article  CAS  Google Scholar 

  75. Floyd RA (1990) Role of oxygen free radicals in carcinogenesis and brain ischemia. FASEB J 4:2587–2597

    PubMed  CAS  Google Scholar 

  76. Valko M, Morris H, Cronin MTD (2005) Metals, toxicity and oxidative stress. Curr Med Chem 12:1161–1208

    Article  PubMed  CAS  Google Scholar 

  77. Merzenich H, Hartwig A, Ahrens W, Beyersmann D, Schlepegrell R (2001) Biomonitoring on carcinogenic metals and oxidative DNA damage in a cross-sectional study. Cancer Epidemiol Biomarkers Prev 10:515–522

    PubMed  CAS  Google Scholar 

  78. Gate L, Paul J, Ba GN, Tew KD, Tapiero H (1999) Oxidative stress induced in pathologies: the role of antioxidants. Biomed Pharmcother 53:169–180

    Article  CAS  Google Scholar 

  79. Gupte A, Mumper RJ (2009) Elevated copper and oxidative stress in cancer cells as a target for cancer treatment. Cancer Treat Rev 35:32–46

    Article  PubMed  CAS  Google Scholar 

  80. Jackson MJ (2009) Skeletal muscle aging: role of reactive oxygen species. Crit Care Med 37:S368–S371

    Article  PubMed  CAS  Google Scholar 

  81. Auld DS (2001) Zinc coordination sphere in biochemical zinc sites. Biometals 14:271–313

    Article  PubMed  CAS  Google Scholar 

  82. O’Connor JM (2001) Trace elements and DNA damage. Biochem Soc Trans 29:354–357

    Article  PubMed  Google Scholar 

  83. Leccia MT, Richard MJ, Favier A, Beani JC (1999) Zinc protects against ultraviolet A1-induced DNA damage and apoptosis in cultured human fibroblasts. Biol Trace Elem Res 69:177–190

    Article  PubMed  CAS  Google Scholar 

  84. Goldhaber SB (2003) Trace element risk assessment: essentiality vs. toxicity. Regul Toxicol Pharmacol 38:232–242

    Article  PubMed  CAS  Google Scholar 

  85. Torreggiani A, Domenech J, Orihuela R, Ferreri C, Atrian S (2009) Zinc and cadmium complexes of a plant metallothionein under radical stress: desulfurisation reactions associated with the formation of trans-lipids in model membranes. Chem Eur J 15:6015–6024

    Article  CAS  Google Scholar 

  86. Hossain Z, Huq F (2002) Studies on the interaction between Cd(2+) ions and DNA. J Inorg Biochem 90:85–96

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  88. Waalkes MP (2000) Cadmium carcinogenesis in review. J Inorg Chem 79:241–244

    CAS  Google Scholar 

Download references

Acknowledgment

The authors would like to thank Mrs. Smitha Adhip from the Department of Anatomy, Mrs. Alice Babu Mattappallil and Mr. Kanachu Isaac Mathew from the Department of surgery, and Dr. T.S. Kumar from the Department of Biochemistry for their technical help.

Author information

Authors and Affiliations

  1. Department of Anatomy, Faculty of Medicine, Health Science Centre, Kuwait University, P.O. Box 24923, Safat, 13110, Kuwait

    Farid Saleh

  2. Department of Surgery, Faculty of Medicine, Health Science Centre, Kuwait University, P.O. Box 24923, Safat, 13110, Kuwait

    Abdallah Behbehani & Sami Asfar

  3. Department of Biochemistry, Faculty of Medicine, Health Science Centre, Kuwait University, P.O. Box 24923, Safat, 13110, Kuwait

    Islam Khan

  4. Department of Family Medicine, Ministry of Health, Safat, Kuwait

    Ghada Ibrahim

Authors
  1. Farid Saleh
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Abdallah Behbehani
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Sami Asfar
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Islam Khan
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Ghada Ibrahim
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Farid Saleh.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Saleh, F., Behbehani, A., Asfar, S. et al. Abnormal Blood Levels of Trace Elements and Metals, DNA Damage, and Breast Cancer in the State of Kuwait. Biol Trace Elem Res 141, 96–109 (2011). https://doi.org/10.1007/s12011-010-8724-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12011-010-8724-z

Keywords

Search

Navigation