Metallothioneins and zinc in cancer diagnosis and therapy

Drug Metabolism Reviews

Volumn 44, Issue 4, 2012, Pages 287-301

  Krizkova, Sona ^a,b   Ryvolova, Marketa ^a,b   Hrabeta, Jan ^c   Adam, Vojtech ^a,b   Stiborova, Marie ^d   Eckschlager, Tomas ^c   Kizek, Rene ^a,b  

^a MENDEL UNIVERSITY IN BRNO   (Czech Republic)

^b BRNO UNIVERSITY OF TECHNOLOGY   (Czech Republic)

^c UNIVERSITY HOSPITAL MOTOL   (Czech Republic)

^d CHARLES UNIVERSITY   (Czech Republic)

Author keywords

Apoptosis; Cancer; Metallothioneins; NF B; Prognostic factor; Protein p53; Resistance; Tumor marker; Zinc

Indexed keywords

CISPLATIN; COMPLEMENTARY RNA; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; METALLOTHIONEIN; NITRIC OXIDE; PROTEIN KINASE C; PROTEIN P53; SMALL INTERFERING RNA; ZINC; ZINC FINGER PROTEIN;

APOPTOSIS; CANCER CELL; CANCER DIAGNOSIS; CANCER RESISTANCE; CANCER RISK; CANCER THERAPY; CARCINOGENESIS; CATALYSIS; CELL PROLIFERATION; DNA SYNTHESIS; ENZYME ACTIVATION; ESOPHAGEAL CANCER RELATED GENE; GENE CONTROL; GENE EXPRESSION; GENE SILENCING; GENETIC TRANSCRIPTION; HUMAN; IMMUNOMODULATION; NEUROTRANSMISSION; NONHUMAN; OXIDATION REDUCTION STATE; OXIDATIVE STRESS; PROMOTER REGION; PROTEIN FUNCTION; PROTEIN PROTEIN INTERACTION; PROTEIN STRUCTURE; REVIEW; SIGNAL TRANSDUCTION; TUMOR SUPPRESSOR GENE; ZINC METABOLISM;

ANIMALS; ANTINEOPLASTIC AGENTS; APOPTOSIS; CELL PROLIFERATION; HUMANS; IMMUNOMODULATION; METALLOTHIONEIN; MOLECULAR TARGETED THERAPY; NEOPLASM PROTEINS; NEOPLASMS; NITRIC OXIDE; OXIDATIVE STRESS; PROGNOSIS; TUMOR MARKERS, BIOLOGICAL; ZINC;

EID: 84870798861     PISSN: 03602532     EISSN: 10979883     Source Type: Journal    
DOI: 10.3109/03602532.2012.725414     Document Type: Review

References (223)

1. Abdel-Mageed, A. B., Agrawal, K. C. (1998). Activation of nuclear factor kappa B: potential role in metallothionein-mediated mitogenic response. Cancer Res 58:2335-2338.
2. Abdel-Mageed, A. B., Zhao, F. S., Rider, B. J., Agrawal, K. C. (2003). Erythropoietin-induced metallothionein gene expression: role in proliferation of K562 cells. Exp Biol Med 228:1033-1039.
3. Abdelmageed, A. B., Agrawal, K. C. (1997). Antisense down-regulation of metallothionein induces growth arrest and apoptosis in human breast carcinoma cells. Cancer Gene Ther 4:199-207.
4. Adam, V., Blastik, O., Krizkova, S., Lubal, P., Kukacka, J., Prusa, R., et al. (2008). Application of the Brdicka reaction in determination of metallothionein in patients with tumours. Chem Listy 102:51-58.
5. Adam, V., Fabrik, I., Eckschlager, T., Stiborova, M., Trnkova, L., Kizek, R. (2010). Vertebrate metallothioneins as target molecules for analytical techniques. TRAC-Trends Anal Chem 29:409-418.
6. Ames, B. N. (2001). DNA damage from micronutrient deficiencies is likely to be a major cause of cancer. Mutat Res 475:7-20.
7. Apostolova, M. D., Chen, S. L., Chakrabarti, S., Cherian, M. G. (2001). High-glucose-induced metallothionein expression in endothelial cells: an endothelin-mediated mechanism. Am J Physiol Cell Physiol 281:C899-C907.
8. Apostolova, M. D., Cherian, M. G. (2000). Delay of M-phase onset by aphidicolin can retain the nuclear localization of zinc and metallothionein in 3T3-L1 fibroblasts. J Cell Physiol 183:247-253.
9. Arriaga, J. M., Levy, E. M., Bravo, A. I., Bayo, S. M., Amat, M., Aris, M., et al. (2012). Metallothionein expression in colorectal cancer: relevance of different isoforms for tumor progression and patient survival. Hum Pathol 43:197-208.
10. Ba, L. A., Doering, M., Burkholz, T., Jacob, C. (2009). Metal trafficking: from maintaining the metal homeostasis to future drug design. Metallomics 1:292-311.
11. Babula, P., Kohoutkova, V., Opatrilova, R., Dankova, I., Masarik, M., Kizek, R. (2011). Pharmaceutical importance of zinc and metallothionein in cell signalling. Chim Oggi Chem Today 28:18-21.
12. Bagheri, P. M., Govaerts, I., De Ley, M. (2011). Role of metallothionein in differentiation of leukemia cells. Mol Biol Rep 38:3017-3022.
13. Baird, S. K., Kurz, T., Brunk, U. T. (2006). Metallothionein protects against oxidative stress-induced lysosomal destabilization. Biochem J 394:275-283.
14. Banerjee, D., Onosaka, S., Cherian, M. G. (1982). Immunohistochemical localization of metallothionein in cell-nucleus and cytoplasm of rat-liver and kidney. Toxicology 24:95-105.
15. Berendji, D., Kolbbachofen, V., Meyer, K. L., Grapenthin, O., Weber, H., Wahn, V., et al. (1997). Nitric oxide mediates intracytoplasmic and intranuclear zinc release. FEBS Lett 405:37-41.
16. Beyersmann, D., Hartwig, A. (2008). Carcinogenic metal compounds: recent insight into molecular and cellular mechanisms. Arch Toxicol 82:493-512.
17. Binet, M. R. B., Cruz-Ramos, H., Laver, J., Hughes, M. N., Poole, R. K. (2002). Nitric oxide releases intracellular zinc from prokaryotic metallothionein in Escherichia coli. FEMS Microbiol Lett 213:121-126.
18. Bofill, R., Capdevila, M., Atrian, S. (2009). Independent metal-binding features of recombinant metallothioneins convergently draw a step gradation between Zn-and Cu-thioneins. Metallomics 1:229-234.
19. Borghesi, L. A., Lynes, M. A. (1996). Nonprotective effects of extracellular metallothionein. Toxicol Appl Pharmacol 139:6-14.
20. Borghesi, L. A., Youn, J., Olson, E. A., Lynes, M. A. (1996). Interactions of metallothionein with murine lymphocytes: plasma membrane binding and proliferation. Toxicology 108:129-140.
21. Boulikas, T., Vougiouka, M. (2003). Cisplatin and platinum drugs at the molecular level. (Review). Oncol Rep 10:1663-1682.
22. Bredel, M. (2001). Anticancer drug resistance in primary human brain tumors. Brain Res Rev 35:161-204.
23. Brewer, G. J. (2009). Zinc and tetrathiomolybdate for the treatment of Wilson's disease and the potential efficacy of anticopper therapy in a wide variety of diseases. Metallomics 1:199-206.
24. Butcher, H. L., Kennette, W. A., Collins, O., Zalups, R. K., Koropatnick, J. (2004). Metallothionein mediates the level and activity of nuclear factor kappa B in murine fibroblasts. J Pharmacol Exp Ther 310:589-598.
25. Cai, L., Satoh, M., Tohyama, C., Cherian, M. G. (1999). Metallothionein in radiation exposure: its induction and protective role. Toxicology 132:85-98.
26. Canogauci, D. F., Sarkar, B. (1996). Reversible zinc exchange between metallothionein and the estrogen receptor zinc finger. FEBS Lett 386:1-4.
27. Capdevila, M., Bofill, R., Palacios, O., Atrian, S. (2012). State-of-the-art of metallothioneins at the beginning of the 21st century. Coord Chem Rev 256:46-62.
28. Cardoso, S. V., Silveira, J. B., Machado, V. D., De-Paula, A. M. B., Loyola, A. M., De Aguiar, M. C. F. (2009). Expression of metallothionein and p53 antigens are correlated in oral squamous cell carcinoma. Anticancer Res 29:1189-1193.
29. Chakraborty, T., Chatterjee, A., Rana, A., Srivastawa, S., Damodaran, S., Chatterjee, M. (2007). Cell proliferation and hepatocarcinogenesis in rat initiated by diethylnitrosamine and promoted by phenobarbital: potential roles of early DNA damage and liver metallothionein expression. Life Sci 81:489-499.
30. Chao, C. C. K. (1996). Molecular basis of cisdiamminedichloroplatinum( II) resistance: a review. J Formos Med Assoc 95:893-900.
31. Chen, M. D., Song, Y. M. (2009). Tissue metallothionein concentrations in mice and humans with hyperglycemia. Biol Trace Elem Res 127:251-256.
32. Chen, W. Y., John, J. A., Lin, C. H., Chang, C. Y. (2007). Expression pattern of metallothionein, MTF-1 nuclear translocation, and its DNA-binding activity in zebrafish (Danio rerio) induced by zinc and cadmium. Environ Toxicol Chem 26:110-117.
33. Chen, W. Y., John, J. A., Lin, C. H., Lin, H. F., Wu, S. C., Chang, C. Y. (2004). Expression of metallothionein gene during embryonic and early larval development in zebrafish. Aquat Toxicol 69:215-227.
34. Cherian, M. G., Apostolova, M. D. (2000). Nuclear localization of metallothionein during cell proliferation and differentiation. Cell Mol Biol 46:347-356.
35. Cherian, M. G., Jayasurya, A., Bay, B. H. (2003). Metallothioneins in human tumors and potential roles in carcinogenesis. Mutat Res 533:201-209.
36. Chiaverini, N., De Ley, M. (2010). Protective effect of metallothionein on oxidative stress-induced DNA damage. Free Radic Res 44:605-613.
37. Chong, C. R., Auld, D. S. (2007). Catalysis of zinc transfer by D-penicillamine to secondary chelators. J Med Chem 50:5524-5527.
38. Chubatsu, L. S., Meneghini, R. (1993). Metallothionein protects DNA from oxidative damage. Biochem J 291:193-198.
39. Coleman, J. E. (1992). Zinc proteins-enzymes, storage proteins, transcription factors, and replication proteins. Annu Rev Biochem 61:897-946.
40. Colvin, R. A., Holmes, W. R., Fontaine, C. P., Maret, W. (2010). Cytosolic zinc buffering and muffling: their role in intracellular zinc homeostasis. Metallomics 2:306-317.
41. Coyle, P., Philcox, J. C., Carey, L. C., Rofe, A. M. (2002). Metallothionein: the multipurpose protein. Cell Mol Life Sci 59:627-647.
42. Crowthers, K. C., Kline, V., Giardina, C., Lynes, M. A. (2000). Augmented humoral immune function in metallothionein-null mice. Toxicol Appl Pharmacol 166:161-172.
43. Cui, Y. P., Wang, J. B., Zhang, X. Y., Lang, R. G., Bi, M. X., Guo, L. P., et al. (2003). ECRG2, a novel candidate of tumor suppressor gene in the esophageal carcinoma, interacts directly with metallothionein 2A and links to apoptosis. Biochem Biophys Res Commun 302:904-915.
44. Culotta, V. C., Hamer, D. H. (1989). Fine mapping of a mouse metallothionein gene metal response element. Mol Cell Biol 9:1376-1380.
45. Cummings, J. E., Kovacic, J. P. (2009). The ubiquitous role of zinc in health and disease. J Vet Emerg Crit Care 19:215-240.
46. Dhawan, D. K., Chadha, V. D. (2010). Zinc: a promising agent in dietary chemoprevention of cancer. Indian J Med Res 132:676-682.
47. Ding, Z. C., Ni, F. Y., Huang, Z. X. (2010). Neuronal growth-inhibitory factor (metallothionein-3): structure-function relationships. FEBS J, 277:2912-2920.
48. Dutsch-Wicherek, M. (2010). RCAS1, MT, and Vimentin as potential markers of tumor microenvironment remodeling. Am J Reprod Immunol 63:181-188.
49. Dutsch-Wicherek, M., Sikora, J., Tomaszewska, R. (2008). The possible biological role of metallothionein in apoptosis. Front Biosci 13:4029-4038.
50. Ebadi, M., Elsayed, M. A., Aly, M. H. M. (1993). Actions and regulation of protein-kinase-C in brain. Neuroendocrinol Lett 15:69-88.
51. Eckschlager, T., Adam, V., Hrabeta, J., Figova, K., Kizek, R. (2009). Metallothioneins and cancer. Curr Protein Pept Sci 10:360-375.
52. Eide, D. J. (2011). The oxidative stress of zinc deficiency. Metallomics 3:1124-1129.
53. Ejnik, J., Munoz, A., Gan, T., Shaw, C. F., Petering, D. H. (1999). Interprotein metal ion exchange between cadmium-carbonic anhydrase and apo-or zinc-metallothionein. J Biol Inorg Chem 4:784-790.
54. El Sharkawy, S. L., Abbas, N. F., Badawi, M. A., El Shaer, M. A. (2006). Metallothionein isoform II expression in hyperplastic, dysplastic, and neoplastic prostatic lesions. J Clin Pathol 59:1171-1174.
55. Faller, P. (2010). Neuronal growth-inhibitory factor (metallothionein-3): reactivity and structure of metal-thiolate clusters. FEBS J 277:2921-2930.
56. Faller, W. J., Rafferty, M., Hegarty, S., Gremel, G., Ryan, D., Fraga, M. F., et al. (2010). Metallothionein 1E is methylated in malignant melanoma and increases sensitivity to cisplatin-induced apoptosis. Melanoma Res 20:392-400.
57. Fan, L. Z., Cherian, M. G. (2002). Potential role of p53 on metallothionein induction in human epithelial breast cancer cells. Br J Cancer 87:1019-1026.
58. Fang, Y. Z., Yang, S., Wu, G. Y. (2002). Free radicals, antioxidants, and nutrition. Nutrition 18:872-879.
59. Feng, W., Cai, J., Pierce, W. M., Franklin, R. B., Maret, W., Benz, F. W., et al. (2005). Metallothionein transfers zinc to mitochondrial aconitase through a direct interaction in mouse hearts. Biochem Biophys Res Commun 332:853-858.
60. Fong, L. Y. Y., Jiang, Y. B., Farber, J. L. (2006). Zinc deficiency potentiates induction and progression of lingual and esophageal tumors in p53-deficient mice. Carcinogenesis 27:1489-1496.
61. Formigare, A., Irato, P., Santon, A. (2007a). Zinc, antioxidant systems, and metallothionein in metal mediated-apoptosis: biochemical and cytochemical aspects. Comp Biochem Physiol C Toxicol Pharmacol 146:443-459.
62. Formigari, A., Santon, A., Irato, P. (2007b). Efficacy of zinc treatment against iron-induced toxicity in rat hepatoma cell line H4-II-E-C3. Liver Int 27:120-127.
63. Franklin, R. B., Costello, L. C. (2007). Zinc as an anti-tumor agent in prostate cancer and in other cancers. Arch Biochem Biophys 463:211-217.
64. Franklin, R. B., Costello, L. C. (2009). The important role of the apoptotic effects of zinc in the development of cancers. J Cell Biochem 106:750-757.
65. Frederickson, C. J., Koh, J. Y., Bush, A I. (2005). The neurobiology of zinc in health and disease. Nat Rev Neurosci 6:449-462.
66. Fukada, T., Yamasaki, S., Nishida, K., Murakami, M., Hirano, T. (2011). Zinc homeostasis and signaling in health and diseases. J Biol Inorg Chem 16:1123-1134.
67. Futakawa, N., Kondoh, M., Ueda, S., Higashimoto, M., Takiguchi, M., Suzuki, S., et al. (2006). Involvement of oxidative stress in the synthesis of metallothionein induced by mitochondrial inhibitors. Biol Pharm Bull 29:2016-2020.
68. Ghoshal, K., Jacob, S. T. (2001). Regulation of metallothionein gene expression. Prog Nucleic Acid Res Mol Biol 66:357-384.
69. Ghoshal, K., Majumder, S., Jacob, S. T. (2002). Analysis of promoter methylation and its role in silencing metallothionein I gene expression in tumor cells. Redox Cell Biol Genetics Pt B 353:476-486.
70. Gomulkiewicz, A., Podhorska-Okolow, M., Szulc, R., Smorag, Z., Wojnar, A., Zabel, M., et al. (2010). Correlation between metallothionein (MT) expression and selected prognostic factors in ductal breast cancers. Folia Histochem Cytobiol 48:242-248.
71. Gosland, M., Lum, B., Schimmelpfennig, J., Baker, J., Doukas, M. (1996). Insights into mechanisms of cisplatin resistance and potential for its clinical reversal. Pharmacotherapy 16:16-39.
72. Grant, W. B. (2008). An ecological study of cancer mortality rates including indices for dietary iron and zinc. Anticancer Res 28:1955-1963.
73. Gumulec, J., Masarik, M., Krizkova, S., Adam, V., Hubalek, J., Hrabeta, J., et al. (2011). Insight to physiology and pathology of zinc(II) ions and their actions in breast and prostate carcinoma. Curr Med Chem 18:5041-5051.
74. Gunes, C., Heuchel, R., Georgiev, O., Muller, K. H., Lichtlen, P., Bluthmann, H., et al. (1998). Embryonic lethality and liver degeneration in mice lacking the metal-responsive transcriptional activator MTF-1. EMBO J 17:2846-2854.
75. Hafsi, H., Hainaut, P. (2011). Redox control and interplay between p53 isoforms: roles in the regulation of basal p53 levels, cell fate, and senescence. Antioxid Redox Signal 15:1655-1667.
76. Haga, A., Nagase, H., Kito, H., Sato, T. (1996). Effect of metallothioneins on collagenolytic activity of tumor gelatinase B. Cancer Res Ther Ctrl 5:17-22.
77. Haga, A., Nagase, H., Kito, H., Sato, T. (1997). Invasive properties of cadmium-resistant human fibrosarcoma HT-1080 cells. Cancer Biochem Biophys 15:275-284.
78. Hainaut, P., Mann, K. (2001). Zinc binding and redox control of p53 structure and function. Antioxid Redox Signal 3:611-623.
79. Hao, Q., Maret, W. (2005). Imbalance between pro-oxidant and pro-antioxidant functions of zinc in disease. J Alzheimers Dis 8:161-170.
80. Ho, E. (2004). Zinc deficiency, DNA damage, and cancer risk. J Nutr Biochem 15:572-578.
81. Hogstrand, C., Kille, P., Nicholson, R. I., Taylor, K. M. (2009). Zinc transporters and cancer: a potential role for ZIP7 as a hub for tyrosine kinase activation. Trends Mol Med 15:101-111.
82. Huang, M., Shaw, C. F., Petering, D. H. (2004). Interprotein metal exchange between transcription factor IIIa and apometallothionein. J Inorg Biochem 98:639-648.
83. Huang, Z. X. (2010). Neuronal growth-inhibitory factor (metallothionein-3): a unique metalloprotein. FEBS J 277:2911.
84. Il'yasova, D., Schwartz, G. G. (2005). Cadmium and renal cancer. Toxicol Appl Pharmacol 207:179-186.
85. Iwata, M., Takebayashi, T., Ohta, H., Alcalde, R. E., Itano, Y., Matsumura, T. (1999). Zinc accumulation and metallothionein gene expression in the proliferating epidermis during wound healing in mouse skin. Histochem Cell Biol 112:283-290.
86. Jamieson, A. C., Miller, J. C., Pabo, C. O. (2003). Drug discovery with engineered zinc-finger proteins. Nat Rev Drug Discov 2:361-368.
87. Jasani, B., Schmid, K. W. (1997). Significance of metallothionein overexpression in human. Histopathology 31:211-214.
88. Jason, T. L. H., Koropatnick, J., Berg, R. W. (2004). Toxicology of antisense therapeutics. Toxicol Appl Pharmacol 201:66-83.
89. Jayasurya, A., Bay, B. H., Yap, W. M., Tan, N. G., Tan, B. K. H. (2000). Proliferative potential in nasopharyngeal carcinoma: correlations with metallothionein expression and tissue zinc levels. Carcinogenesis 21:1809-1812.
90. Jin, R. X., Huang, J. X., Tan, P. H., Bay, B. H. (2004). Clinicopathological significance of metallothioneins in breast cancer. Pathol Oncol Res 10:74-79.
91. Jin, R. X., Chow, V. T. K., Tan, P. H., Dheen, S. T., Duan, W., Bay, B. H. (2002). Metallothionein 2A expression is associated with cell proliferation in breast cancer. Carcinogenesis 23:81-86.
92. John, E., Laskow, T. C., Buchser, W. J., Pitt, B. R., Basse, P. H., Butterfield, L. H., et al. (2010a). Zinc in innate and adaptive tumor immunity. J Transl Med 8:1-16.
93. John, S., Briatka, T., Rudolf, E. (2010b). Diverse sensitivity of cells representing various stages of colon carcinogenesis to increased extracellular zinc: implications for zinc chemoprevention. Oncol Rep 25:769-780.
94. Kagi, J. H. R., Schaffer, A. (1988). Biochemistry of metallothionein. Biochemistry 27:8509-8515.
95. Kaibori, M., Sakitani, K., Oda, M., Kamiyama, Y., Masu, Y., Nishizawa, M., et al. (1999). Immunosuppressant FK506 inhibits inducible nitric oxide synthase gene expression at a step of NF-Î?B activation in rat hepatocytes. J Hepatol 30:1138-1145.
96. Karasawa, M., Nishimura, N., Nishimura, H., Tohyama, C., Hashiba, H., Kuroki, T. (1991). Localization of metallothionein in hair-follicles of normal skin and the basal-cell layer of hyperplastic epidermis-possible association with cell-proliferation. J Invest Dermatol 97:97-100.
97. Karin, M., Eddy, R. L., Henry, W. M., Haley, L. L., Byers, M. G., Shows, T. B. (1984). Human metallothionein genes are clustered on chromosome-16. Proc Natl Acad Sci USA 81:5494-5498.
98. Kennette, W., Collins, O. M., Zalups, R. K., Koropatnick, J. (2005). Basal and zinc-induced metallothionein in resistance to cadmium, cisplatin, zinc, and tertButyl hydroperoxide: studies using MT knockout and antisense-downregulated MT in mammalian cells. Toxicol Sci 88:602-613.
99. Kim, H. G., Kim, J. Y., Han, E. H., Hwang, Y. P., Choi, J. H., Park, B. H., et al. (2011). Metallothionein-2A overexpression increases the expression of matrix metalloproteinase-9 and invasion of breast cancer cells. FEBS Lett 585:421-428.
100. Kim, C. H., Kim, J. H., Lee, J., Ahn, Y. S. (2003). Zinc-induced NF-kappa B inhibition can be modulated by changes in the intracellular metallothionein level. Toxicol Appl Pharmacol 190:189-196.
101. Kimura, T. (2010). Molecular mechanisms of zinc-mediated induction and chromium(VI)-mediated inhibition of mouse metallothionein-I gene transcription. J Health Sci 56:161-166.
102. Klaassen, C. D., Choudhuri, S., McKim, J. M., Lehmanmckeeman, L. D., Kershaw, W. C. (1994). In-vitro and in-vivo studies on the degradation of metallothionein. Environ Health Perspect 102:141-146.
103. Klaassen, C. D., Liu, J., Diwan, B. A. (2009). Metallothionein protection of cadmium toxicity. Toxicol Appl Pharmacol 238:215-220.
104. Klassen, R. B., Crenshaw, K., Kozyraki, R., Verroust, P. J., Tio, L., Atrian, S., et al. (2004). Megalin mediates renal uptake of heavy metal metallothionein complexes. Am J Physiol Renal Physiol 287:F393-F403.
105. Knipp, M. (2009). Metallothioneins and platinum(II) anti-tumor compounds. Curr Med Chem 16:522-537.
106. Knipp, M., Meloni, G., Roschitzki, B., Vasak, M. (2005). Zn(7) metallothionein-3 and the synaptic vesicle cycle: interaction of metallothionein-3 with the small GTPase Rab3A. Biochemistry 44:3159-3165.
107. Ko, Y. H., Woo, Y. J., Kim, J. W., Choi, H., Kang, S. H., Lee, J. G., et al. (2010). High-dose dietary zinc promotes prostate intraepithelial neoplasia in a murine tumor induction model. Asian J Androl 12:164-170.
108. Koizumi, S., Yamada, H. (2003). DNA microarray analysis of altered gene expression in cadmium-exposed human cells. J Occup Health 45:331-334.
109. Kondo, Y., Rusnak, J. M., Hoyt, D. G., Settineri, C. E., Pitt, B. R., Lazo, J. S. (1997). Enhanced apoptosis in metallothionein null cells. Mol Pharmacol 52:195-201.
110. Kothinti, R., Blodgett, A., Tabatabai, N. M., Petering, D. H. (2010). Zinc finger transcription factor Zn(3)-SP1 reactions with Cd(2+). Chem Res Toxicol 23:405-412.
111. Krejcova, L., Fabrik, I., Hynek, D., Krizkova, S., Gumulec, J., Ryvolova, M., et al. (2012). Metallothionein electrochemically determined using Brdicka reaction as a promising blood marker of head and neck malignant tumours. Int J Electrochem Sci 7:1767-1784.
112. Krezel, A., Maret, W. G. (2008). Thionein/metallothionein control Zn(II) availability and the activity of enzymes. J Biol Inorg Chem 13:401-409.
113. Krizkova, S., Fabrik, I., Adam, V., Hrabeta, P., Eckschlager, T., Kizek, R. (2009). Metallothionein-a promising tool for cancer diagnostics. Bratisl Med J 110:93-97.
114. Krizkova, S., Fabrik, I., Adam, V., Kukacka, J., Prusa, R., Chavis, G. J., et al. (2008). Utilizing of adsorptive transfer stripping technique Brdicka reaction for determination of metallothioneins level in melanoma cells, blood serum, and tissues. Sensors 8:3106-3122.
115. Krizkova, S., Masarik, M., Majzlik, P., Kukacka, J., Kruseova, J., Adam, V., et al. (2010). Serum metallothionein in newly diagnosed patients with childhood solid tumours. Acta Biochim Pol 57:561-566.
116. Krizkova, S., Ryvolova, M., Gumulec, J., Masarik, M., Adam, V., Majzlik, P., et al. (2011). Electrophoretic fingerprint metallothionein analysis as a potential prostate cancer biomarker. Electrophoresis 32:1952-1961.
117. Krizkova, S., Ryvolova, M., Hynek, D., Eckschlager, T., Hodek, P., Masarik, M., et al. (2012). Immunoextraction of zinc proteins from human plasma using chicken yolk antibodies immobilized onto paramagnetic particles and their electrophoretic analysis. Electrophoresis 2012;33:1824-1832.
118. Krolicka, A., Kobierzycki, C., Pula, B., Podhorska-Okolow, M., Piotrowska, A., Rzeszutko, M., et al. (2010). Comparison of metallothionein (MT) and Ki-67 antigen expression in benign and malignant thyroid tumours. Anticancer Res 30:4945-4949.
119. Kroncke, K. D. (2001). Zinc finger proteins as molecular targets for nitric oxide-mediated gene regulation. Antioxid Redox Signal 3:565-575.
120. Kroncke, K. D., Fehsel, K., Schmidt, T., Zenke, F. T., Dasting, I., Wesener, J. R., et al. (1994). Nitric-oxide destroys zinc-sulfur clusters inducing zinc release from metallothionein and inhibition of the zinc finger-type yeast transcription activator lac9. Biochem Biophys Res Commun 200:1105-1110.
121. Kuppens, K., De Ley, M. (2006). Serum-induced expression of metallothionein isoforms in K-562 cells. Biochem Biophys Res Commun 342:979-983.
122. Kuroda, S., Tokunaga, C., Kiyohara, Y., Higuchi, O., Konishi, H., Mizuno, K., et al. (1996). Protein-protein interaction of zinc finger LIM domains with protein kinase C. J Biol Chem 271:31029-31032.
123. Lai, Y. Y., Lim, D. N., Tan, P. H., Leung, T. K. C., Yip, G. W. C., Bay, B. H. (2010). Silencing the metallothionein-2A gene induces entosis in adherent MCF-7 breast cancer cells. Anat Rec 293:1685-1691.
124. Lai, Y. Y., Yip, G. W. C., Bay, B. H. (2011). Targeting metallothionein for prognosis and treatment of breast cancer. Recent Pat Anticancer Drug Discov 6:178-185.
125. Lee, S. J., Park, M. H., Kim, H. J., Koh, J. Y. (2010). Metallothionein-3 regulates lysosomal function in cultured astrocytes under both normal and oxidative conditions. Glia, 58, 1186-96.
126. Lee, Y. C., Wang, H. P., Wang, C. P., Ko, J. Y., Lee, J. M., Chiu, H. M., et al. (2011). Revisit of field cancerization in squamous cell carcinoma of upper aerodigestive tract: better risk assessment with epigenetic markers. Cancer Prev Res 4:1982-1992.
127. Lindeque, J. Z., Levanets, O., Louw, R., Van Der Westhuizen, F. H. (2010). The involvement of metallothioneins in mitochondrial function and disease. Curr Protein Pept Sci 11:292-309.
128. Liu, J., Qu, W., Kadiiska, M. B. (2009). Role of oxidative stress in cadmium toxicity and carcinogenesis. Toxicol Appl Pharmacol 238:209-214.
129. Luparello, C., Sirchia, R., Longo, A. (2011). Cadmium as a transcriptional modulator in human cells. Crit Rev Toxicol 41:73-80.
130. Lynes, M. A., Borghesi, L. A., Youn, J. H., Olson, E. A. (1993). Immunomodulatory activities of extracellular metallothionein. 1. Metallothionein effects on antibody-production. Toxicology 85:161-177.
131. Lynes, M. A., Zaffuto, K., Unfricht, D. W., Marusov, G., Samson, J. S., Yin, X. Y. (2006). The physiological roles of extracellular metallothionein. Exp Biol Med 231:1548-1554.
132. Malgieri, G., Zaccaro, L., Leone, M., Bucci, E., Esposito, S., Baglivo, I., et al. (2011). Zinc to cadmium replacement in the A. thaliana SUPERMAN Cys(2)His(2) zinc finger induces structural rearrangements of typical DNA base determinant positions. Biopolymers 95:801-810.
133. Malvy, D. J. M., Arnaud, J., Burtschy, B., Sommelet, D., Leverger, G., Dostalova, L., et al. (1997). Antioxidant micronutrients and childhood malignancy during oncological treatment. Med Pediatric Oncol 29:213-217.
134. Malvy, D. J. M., Burtschy, B., Arnaud, J., Sommelet, D., Leverger, G., Dostalova, L., et al. (1993). Serum beta-carotene and antioxidant micronutrients in children with cancer. Int J Epidemiol 22:761-771.
135. Maret, W. (2005). Zinc coordination environments in proteins determine zinc functions. J Trace Elem Med Biol 19:7-12.
136. Maret, W., Jacob, C., Vallee, B. L., Fischer, E. H. (1999). Inhibitory sites in enzymes: zinc removal and reactivation by thionein. Proc Natl Acad Sci USA 96:1936-1940.
137. Maret, W., Krezel, A. (2007). Cellular zinc and redox buffering capacity of metallthionein/thionein in health and disease. Mol Med 13:371-375.
138. Maret, W., Yetman, C. A., Jiang, L. J. (2001). Enzyme regulation by reversible zinc inhibition: glycerol phosphate dehydrogenase as an example. Chem Biol Interact 130:891-901.
139. Margoshes, M., Vallee, B. L. (1957). A cadmium protein from equine kidney cortex. J Am Chem Soc 79:4813-4814.
140. Masarik, M, Gumulec, J, Sztalmachova, M, Hlavna, M, Babula, P, Krizkova, S, et al. (2011). Isolation of metallothionein from cells derived from aggressive form of high-grade prostate carcinoma using paramagnetic antibody-modified microbeads off-line coupled with electrochemical and electrophoretic analysis. Electrophoresis 32:3576-3588.
141. McGee, H. M., Woods, G. M., Bennett, B., Chung, R. S. (2010). The two faces of metallothionein in carcinogenesis: photoprotection against UVR-induced cancer and promotion of tumour survival. Photochem Photobiol Sci 9:586-596.
142. McKim, J. M., Jr., Choudhuri, S., Klaassen, C. D. (1992). In vitro degradation of apo-metallothionein, zinc-metallothionein, and cadmium-metallothionein by cathepsin B, cathepsin C, and cathepsin D. Toxicol Appl Pharmacol 116:117-124.
143. Meplan, C., Hainaut, P. (1999). Molecular alchemy of the tumor suppressor protein p53: metals and cell growth control. J Trace Elem Med Biol 12:337-346.
144. Meplan, C., Richard, M. J., Hainaut, P. (2000). Metalloregulation of the tumor suppressor protein p53: zinc mediates the renaturation of p53 after exposure to metal chelators in vitro and in intact cells. Oncogene 19:5227-5236.
145. Miles, A. T., Hawksworth, G. M., Beattie, J. H., Rodilla, V. (2000). Induction, regulation, degradation, and biological significance of mammalian metallothioneins. Crit Rev Biochem Mol Biol 35:35-70.
146. Mocchegiani, E., Muzzioli, M., Giacconi, R. (2000). Zinc, metallothioneins, immune responses, survival, and ageing. Biogerontology 1:133-143.
147. Morellini, N. M., Giles, N. L., Rea, S., Adcroft, K. F., Falder, S., King, C. E., et al. (2008). Exogenous metallothionein-IIA promotes accelerated healing after a burn wound. Wound Repair Regen 16:682-690.
148. Müller, J. (2010). Functional metal ions in nucleic acids. Metallomics 2:318-327.
149. Murakami, M., Hirano, T. (2008). Intracellular zinc homeostasis and zinc signaling. Cancer Sci 99:1515-1522.
150. Nagano, T., Itoh, N., Ebisutani, C., Takatani, T., Miyoshi, T., Nakanishi, T., et al. (2000). The transport mechanism of metallothionein is different from that of classical NLS-bearing protein. J Cell Physiol 185:440-446.
151. Nagel, W. W., Vallee, B. L. (1995). Cell-cycle regulation of metallothionein in human-colonic cancer cells. Proc Natl Acad Sci USA 92:579-583.
152. Naito, S., Yokomizo, A., Koga, H. (1999). Mechanisms of drug resistance in chemotherapy for urogenital carcinoma. Int J Urol 6:427-439.
153. Namdarghanbari, M., Wobig, W., Krezoski, S., Tabatabai, N. M., Petering, D. H. (2011). Mammalian metallothionein in toxicology, cancer, and cancer chemotherapy. J Biol Inorg Chem 16:1087-1101.
154. Nartey, N., Cherian, M. G., Banerjee, D. (1987). Immunohistochemical localization of metallothionein in human thyroid-tumors. Am J Pathol 129:177-182.
155. Nzengue, Y., Lefebvre, E., Cadet, J., Favier, A., Rachidi, W., Steiman, R., et al. (2009). Metallothionein expression in HaCaT and C6 cell lines exposed to cadmium. J Trace Elem Med Biol 23:314-323.
156. Ogra, Y., Suzuki, K. T. (2000). Nuclear trafficking of metallothionein: possible mechanisms and current knowledge. Cell Mol Biol 46:357-365.
157. Olesen, C., Moller, M., Byskov, A. G. (2004). Tesmin transcription is regulated differently during male and female meiosis. Mol Reprod Dev 67:116-126.
158. Ostrakhovitch, E. A. (2011). Redox environment and its meaning for breast cancer cells fate. Curr Cancer Drug Targets 11:479-495.
159. Ostrakhovitch, E. A., Olsson, P. E., Jiang, S., Cherian, M. G. (2006). Interaction of metallothionein with tumor suppressor p53 protein. FEBS Lett 580:1235-1238.
160. Ostrakhovitch, E. A., Olsson, P. E., Von Hofsten, J., Cherian, M. G. (2007). p53 mediated regulation of metallothionen transcription in breast cancer cells. J Cell Biochem 102:1571-1583.
161. Oyama, T., Takei, H., Hikino, T., Iino, Y., Nakajima, T. (1996). Immunohistochemical expression of metallothionein in invasive breast cancer in relation to proliferative activity, histology and prognosis. Oncology 53:112-117.
162. Palecek, E., Brazdova, M., Cernocka, H., Vlk, D., Brazda, V., Vojtesek, B. (1999). Effect of transition metals on binding of p53 protein to supercoiled DNA and to consensus sequence in DNA fragments. Oncogene 18:3617-3625.
163. Papouli, E., Defais, M., Larminat, F. (2002). Overexpression of metallothionein-II sensitizes rodent cells to apoptosis induced by DNA cross-linking agent through inhibition of NF-kappa B activation. J Biol Chem 277:4764-4769.
164. Pedersen, M. O., Larsen, A., Stoltenberg, M., Penkowa, M. (2009). The role of metallothionein in oncogenesis and cancer prognosis. Prog Histochem Cytochem 44:29-64.
165. Perez, R. P. (1998). Cellular and molecular determinants of cisplatin resistance. Eur J Cancer 34:1535-1542.
166. Plum, L. M., Rink, L., Haase, H. (2010). The essential toxin: impact of zinc on human health. Int J Environ Res Public Health 7:1342-1365.
167. Porteus, M. H., Carroll, D. (2005). Gene targeting using zinc finger nucleases. Nat Biotechnol 23:967-973.
168. Prasad, A. S., Kucuk, O. (2002). Zinc in cancer prevention. Cancer Metastasis Rev 21:291-295.
169. Provinciali, M., Donnini, A., Argentati, K., Di Stasio, G., Bartozzi, B., Bernardini, G. (2002). Reactive oxygen species modulate Zn2+-induced apoptosis in cancer cells. Free Radic Biol Med 32:431-445.
170. Rao, P. S., Jaggi, M., Smith, D. J., Hemstreet, G. P., Balaji, K. C. (2003). Metallothionein 2A interacts with the kinase domain of PKC mu in prostate cancer. Biochem Biophys Res Commun 310:1032-1038.
171. Ribeiro, A. L. R., Nobre, R. M., Rocha, G., Lobato, I. H. D., Alves, S. D., Jaeger, R. G., et al. (2011). Expression of metallothionein in ameloblastoma. A regulatory molecule? J Oral Pathol Med 40:516-519.
172. Rickert, C. H. (2004). Prognosis-related molecular markers in pediatric central nervous system tumors. J Neuropathol Exp Neurol 63:1211-1224.
173. Rickert, C. H., Paulus, W. (2005). Prognosis-related histomorphological and immunohistochemical markers in central nervous system tumors of childhood and adolescence. Acta Neuropathol 109:69-92.
174. Roesijadi, G., Bogumil, R., Vasak, M., Kagi, J. H. R. (1998). Modulation of DNA binding of a tramtrack zinc finger peptide by the metallothionein- thionein conjugate pair. J Biol Chem 273:17425-17432.
175. Rossen, K., Haerslev, T., Houjensen, K., Jacobsen, G. K. (1997). Metallothionein expression in basaloid proliferations overlying dermatofibromas and in basal cell carcinomas. Br J Dermatol 136:30-34.
176. Ryu, M. S., Langkamp-Henken, B., Chang, S. M., Shankar, M. N., Cousins, R. J. (2011). Genomic analysis, cytokine expression, and microRNA profiling reveal biomarkers of human dietary zinc depletion and homeostasis. Proc Natl Acad Sci USA 108:20970-20975.
177. Sato, M., Bremner, I. (1993). Oxygen free-radicals and metallothionein. Free Radic Biol Med 14:325-337.
178. Scanlon, K. J., Kashanisabet, M., Tone, T., Funato, T. (1991). Cisplatin resistance in human cancers. Pharmacol Ther 52:385-406.
179. Searle, P. F., Stuart, G. W., Palmiter, R. D. (1985). Building a metalresponsive promoter with synthetic regulatory elements. Mol Cell Biol 5:1480-1489.
180. Seo, Y. R., Kim, B. J., Ryu, J. C. (2005). Molecular and genomic approaches on nickel toxicity and carcinogenicity. Mol Cell Toxicol 1:73-77.
181. Shami, P. J., Moore, J. O., Gockerman, J. P., Hathorn, J. W., Misukonis, M. A., Weinberg, J. B. (1995). Nitric oxide modulation of the growth and differentiation of freshly isolated acute non-lymphocytic leukemia cells. Leuk Res 19:527-533.
182. Shi, Y. B., Du, L., Zheng, W. J., Tang, W. X. (2002). Isolation of GIF from porcine brain and studies of its zinc transfer kinetics with apocarbonic anhydrase. Biometals 15:421-427.
183. Shi, Y. H., Amin, K., Sato, B. G., Samuelsson, S. J., Sambucetti, L., Haroon, Z. A., et al. (2010). The metal-responsive transcription factor-1 protein is elevated in human tumors. Cancer Biol Ther 9:8.
184. Simpkins, C., Lloyd, T., Li, S., Balderman, S. (1998). Metallothioneininduced increase in mitochondrial inner membrane permeability. J Surg Res 75:30-34.
185. Simpkins, C. O. (2000). Metallothionein in human disease. Cell Mol Biol 46:465-488.
186. Sliwinska-Mosson, M., Milnerowicz, H., Rabczynski, J., Milnerowicz, S. (2009). Immunohistochemical localization of metallothionein and p53 protein in pancreatic serous cystadenomas. Arch Immunol Ther Exp 57:295-301.
187. Sochor, J., Hynek, D., Krejcova, L., Fabrik, I., Krizkova, S., Gumulec, J., et al. (2012). Study of metallothionein role in spinocellular carcinoma tissues of head and neck tumours using Brdicka reaction. Int J Electrochem Sci 7:2136-2152.
188. Soo, E. T. L., Ng, C. T., Yip, G. W. C., Koo, C. Y., Nga, M. E., Tan, P. H., et al. (2011). Differential expression of metallothionein in gastrointestinal stromal tumors and gastric carcinomas. Anat Rec 294:267-272.
189. St Croix, C. M., Wasserloos, K. J., Dineley, K. E., Reynolds, I. J., Levitan, E. S., Pitt, B. R. (2002). Nitric oxide-induced changes in intracellular zinc homeostasis are mediated by metallothionein/thionein. Am J Physiol Lung Cell Mol Physiol 282:L185-L192.
190. Sugiura, T., Yamashita, U. (2000). B cell stimulating activity of metallothionein in vitro. Int J Immunopharmacol 22:113-122.
191. Suzuki, S., Tohma, S., Futakawa, N., Higashimoto, M., Takiguchi, M., Sato, M. (2005). Induction of hepatic metallothionein by mitochondrial oxidative stress in mice. J Health Sci 51:533-537.
192. Takahashi, Y., Ogra, Y., Suzuki, K. T. (2005). Nuclear trafficking of metallothionein requires oxidation of a cytosolic partner. J Cell Physiol 202:563-569.
193. Takeda, A., Hisada, H., Okada, S., Mata, J. E., Ebadi, M., Iversen, P. L. (1997). Tumor cell growth is inhibited by suppressing metallothionein-I synthesis. Cancer Lett 116:145-149.
194. Tan, O. J. K., Bay, B. H., Chow, V. T. K. (2005). Differential expression of metallothionein isoforms in nasopharyneal cancer and inhibition of cell growth by antisense down-regulation of metallothionein-2A. Oncol Rep 13:127-131.
195. Tarapore, P., Shu, Y., Guo, P. X., Ho, S. M. (2011). Application of Phi29 motor pRNA for targeted therapeutic delivery of siRNA silencing metallothionein-IIA and survivin in ovarian cancers. Mol Ther 19:386-394.
196. Theocharis, S, Klijanienko, J, Giaginis, C, Rodriguez, J, Jouffroy, T, Girod, A, et al. (2011). Metallothionein expression in mobile tongue squamous cell carcinoma: associations with clinicopathological parameters and patient survival. Histopathology 59:514-525.
197. Theocharis, S. E., Margeli, A. P., Klijanienko, J. T., Kouraklis, G. P. (2004). Metallothionein expression in human neoplasia. Histopathology 45:103-118.
198. Theocharis, S. E., Margeli, A. P., Koutselinis, A. (2003). Metallothionein: a multifunctional protein from toxicity to cancer. Int J Biol Markers 18:162-169.
199. Thirumoorthy, N., Kumar, K. T. M., Sundar, A. S., Panayappan, L., Chatterjee, M. (2007). Metallothionein: an overview. World J Gastroenterol 13:993-996.
200. Thirumoorthy, N., Sunder, A. S., Kumar, K. T. M., Kumar, M. S., Ganesh, G. N. K., Chatterjee, M. (2011). A review of metallothionein isoforms and their role in pathophysiology. World J Surg Oncol 9:7.
201. Toh, P. P. C., Li, J. J., Yip, G. W. C., Lo, S. L., Guo, C. H., Phan, T. T., et al. (2010). Modulation of metallothionein isoforms is associated with collagen deposition in proliferating keloid fibroblasts in vitro. Exp Dermatol 19:987-993.
202. Tomita, T. (2002). New markers for pancreatic islets and islet cell tumors. Pathol Int 52:425-432.
203. Trieb, K., Kotz, R. (2001). Proteins expressed in osteosarcoma and serum levels as prognostic factors. Int J Biochem Cell Biol 33:11-17.
204. Tsujikawa, K., Imai, T., Kakutani, M., Kayamori, Y., Mimura, T., Otaki, N., et al. (1991). Localization of metallothionein in nuclei of growing primary cultured adult-rat hepatocytes. FEBS Lett 283:239-242.
205. Unal, E., Cavdar, A. O., Babacan, E., Gozdasoglu, S., Yavuz, G., Ikinciogullari, A., et al. (2001). Zinc status and cytokine profile in pediatric Hodgkin's disease. J Trace Elem Med Biol 14:25-30.
206. Vallee, B. L., Coleman, J. E., Auld, D. S. (1991). Zinc fingers, zinc clusters, and zinc twists in DNA-binding protein domains. Proc Natl Acad Sci USA 88:999-1003.
207. Vasak, M., Meloni, G. (2011). Chemistry and biology of mammalian metallothioneins. J Biol Inorg Chem 16:1067-1078.
208. Volm, M. (1998). Multidrug resistance and its reversal. Anticancer Res 18:2905-2917.
209. Vural, S. A., Vural, M. R., Kuplulu, S., Alcigir, M. E., Kaymaz, M. (2009). Immunohistochemical demonstration of p53 protein and metallothioneins in canine mammary tumours. Rev Med Vet 160:300-307.
210. Waalkes, M. P., Rehm, S. (1994). Cadmium and prostate cancer. J Toxicol Environ Health 43:251-269.
211. Waisberg, M., Joseph, P., Hale, B., Beyersmann, D. (2003). Molecular and cellular mechanisms of cadmium carcinogenesis. Toxicology 192:95-117.
212. Wang, C. Y., Cusack, J. C., Liu, R., Baldwin, A S. (1999). Control of inducible chemoresistance: enhanced anti-tumor therapy through increased apoptosis by inhibition of NF-kappa B. Nat Med 5:412-417.
213. Wang, J. X., Yang, J. L. (2010). Interaction of tumor suppressor p53 with DNA and proteins. Curr Pharm Biotechnol 11:122-127.
214. Wlostowski, T. (1993). Involvement of metallothionein and copper in cell-proliferation. Biometals 6:71-76.
215. Woolston, C. M., Deen, S., Al-Attar, A., Shehata, M., Chan, S. Y., Martin, S. G. (2010). Redox protein expression predicts progression-free and overall survival in ovarian cancer patients treated with platinumbased chemotherapy. Free Radic Biol Med 49:1263-1272.
216. Xia, N., Liu, L., Yi, X. Y., Wang, J. X. (2009). Studies of interaction of tumor suppressor p53 with apo-MT using surface plasmon resonance. Anal Bioanal Chem 395:2569-2575.
217. Ye, B., Maret, W., Vallee, B. L. (2001). Zinc metallothionein imported into liver mitochondria modulates respiration. Proc Natl Acad Sci USA 98:2317-2322.
218. Yin, X. Y., Knecht, D. A., Lynes, M. A. (2005). Metallothionein mediates leukocyte chemotaxis. BMC Immunol 6:1-12.
219. Youn, J., Borghesi, L. A., Olson, E. A., Lynes, M. A. (1995). Immunomodulatory activities of extracellular metallothionein. 2. Effect on macrophage functions. J Toxicol Environ Health 45:397-413.
220. Youn, J., Lynes, M. A. (1999). Metallothionein-induced suppression of cytotoxic T lymphocyte function: an important immunoregulatory control. Toxicol Sci 52:199-208.
221. Zeng, J., Vallee, B. L., Kagi, J. H. R. (1991). Zinc transfer from transcription factor-IIIa fingers to thionein clusters. Proc Natl Acad Sci USA 88:9984-9988.
222. Zitka, O., Kukacka, J., Krizkova, S., Huska, D., Adam, V., Masarik, M., et al. (2010). Matrix metalloproteinases. Curr Med Chem, 17, 3751-68.
223. Zuo, X. L., Chen, J. M., Zhou, X., Li, X. Z., Mei, G. Y. (2006). Levels of selenium, zinc, copper, and antioxidant enzyme activity in patients with leukemia. Biol Trace Elem Res, 114, 41-53.