Iron overload and its association with cancer risk in humans: Evidence for iron as a carcinogenic metal

Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis

Volumn 533, Issue 1-2, 2003, Pages 153-171

  Huang, Xi ^a  

^a NEW YORK UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

Cancer; Hemochromatosis; Iron; Oxidative damage; Tumor suppressor genes

Indexed keywords

CARCINOGEN; CHELATING AGENT; CYTOKINE; DEFERIPRONE; DEFEROXAMINE; IRON; METAL; OXIDIZING AGENT; OXYGEN; SIDEROPHORE; TRANSCRIPTION FACTOR; TUMOR MARKER;

AUTOOXIDATION; CANCER RISK; CARCINOGENESIS; CELL CULTURE; CLINICAL TRIAL; COLORECTAL CARCINOMA; DRUG EFFECT; EPIDEMIOLOGICAL DATA; HUMAN; HYPOXIA; IRON CHELATION; IRON OVERLOAD; KIDNEY CARCINOMA; LIVER CARCINOMA; LUNG CARCINOMA; MOLECULAR DYNAMICS; NEUROBLASTOMA; NONHUMAN; OXIDATION REDUCTION REACTION; PH; PHYSICAL CHEMISTRY; PRIORITY JOURNAL; REVIEW; SIGNAL TRANSDUCTION; SINGLE DRUG DOSE; STOMACH CARCINOMA; TREATMENT OUTCOME;

ANIMALIA;

EID: 0345708218     PISSN: 00275107     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.mrfmmm.2003.08.023     Document Type: Review

References (223)

1. Stojiljkovic I., Perkins-Balding D. Processing of heme and heme-containing proteins by bacteria. DNA Cell Biol. 21:2002;281-295.
2. Toth I., Yuan L., Rogers J.T., Boyce H., Bridges K.R. Hypoxia alters iron-regulatory protein-1 binding capacity and modulates cellular iron homeostasis in human hepatoma and erythroleukemia cells. J. Biol. Chem. 274:1999;4467-4473.
3. Eisenstein R.S., Ross K.L. Novel roles for iron regulatory proteins in the adaptive response to iron deficiency. J. Nutr. 133:2003;1510S-1516S.
4. Fleming M.D., Trenor C.C. III, Su M.A., Foernzler D., Beier D.R., Dietrich W.F., Andrews N.C. Microcytic anaemia mice have a mutation in Nramp2, a candidate iron transporter gene. Nat. Genet. 16:1997;383-386.
5. Gunshin H., Mackenzie B., Berger U.V., Gunshin Y., Romero M.F., Boron W.F., Nussberger S., Gollan J.L., Hediger M.A. Cloning and characterization of a mammalian proton-coupled metal-ion transporter. Nature. 388:1997;482-488.
6. Donovan A., Brownlie A., Zhou Y., Shepard J., Pratt S.J., Moynihan J., Paw B.H., Drejer A., Barut B., Zapata A., Law T.C., Brugnara C., Lux S.E., Pinkus G.S., Pinkus J.L., Kingsley P.D., Palis J., Fleming M.D., Andrews N.C., Zon L.I. Positional cloning of zebrafish ferroportin1 identifies a conserved vertebrate iron exporter. Nature. 403:2000;776-781.
7. Ludwiczek S., Aigner E., Theurl I., Weiss G. Cytokine-mediated regulation of iron transport in human monocytic cells. Blood. 101:2003;4148-4154.
8. Dautry-Varsat A., Ciechanover A., Lodish H.F. pH and the recycling of transferrin during receptor-mediated endocytosis. Proc. Natl. Acad. Sci. U.S.A. 80:1983;2258-2262.
9. Paterson S., Armstrong N.J., Iacopetta B.J., McArdle H.J., Morgan E.H. Intravesicular pH and iron uptake by immature erythroid cells. J. Cell Physiol. 120:1984;225-232.
10. Yamashiro D.J., Tycko B., Fluss S.R., Maxfield F.R. Segregation of transferrin to a mildly acidic (pH 6.5) para-Golgi compartment in the recycling pathway. Cell. 37:1984;789-800.
11. Sipe D.M., Murphy R.F. Binding to cellular receptors results in increased iron release from transferrin at mildly acidic pH. J. Biol. Chem. 266:1991;8002-8007.
12. Bali P.K., Zak O., Aisen P. A new role for the transferrin receptor in the release of iron from transferrin. Biochemistry. 30:1991;324-328.
13. Lesnefsky E.J. Tissue iron overload and mechanisms of iron-catalyzed oxidative injury. Adv. Exp. Med. Biol. 366:1994;129-146.
14. Koeller D.M., Horowitz J.A., Casey J.L., Klausner R.D., Harford J.B. Translation and the stability of mRNAs encoding the transferrin receptor and c-fos. Proc. Natl. Acad. Sci. U.S.A. 88:1991;7778-7782.
15. Eisenstein R.S., Blemings K.P. Iron regulatory proteins, iron responsive elements and iron homeostasis. J. Nutr. 128:1998;2295-2298.
16. Kaplan J. Mechanisms of cellular iron acquisition: another iron in the fire. Cell. 111:2002;603-606.
17. Jacobs A. Low molecular weight intracellular iron transport compounds. Blood. 50:1977;433-439.
18. Breuer W., Epsztejn S., Cabantchik Z.I. Dynamics of the cytosolic chelatable iron pool of K562 cells. FEBS Lett. 382:1996;304-308.
19. Miller L.L., Miller S.C., Torti S.V., Tsuji Y., Torti F.M. Iron-independent induction of ferritin H chain by tumor necrosis factor. Proc. Natl. Acad. Sci. U.S.A. 88:1991;4946-4950.
20. Cabantchik Z.I., Glickstein H., Milgram P., Breuer W. A fluorescence assay for assessing chelation of intracellular iron in a membrane model system and in mammalian cells. Anal. Biochem. 233:1996;221-227.
21. Breuer W., Ermers M.J., Pootrakul P., Abramov A., Hershko C., Cabantchik Z.I. Desferrioxamine-chelatable iron, a component of serum non-transferrin- bound iron, used for assessing chelation therapy. Blood. 97:2001;792-798.
22. Petrat F., Rauen U., de Groot H. Determination of the chelatable iron pool of isolated rat hepatocytes by digital fluorescence microscopy using the fluorescent probe, phen green SK. Hepatology. 29:1999;1171-1179.
23. Thomas F., Serratrice G., Beguin C., Aman E.S., Pierre J.L., Fontecave M., Laulhere J.P. Calcein as a fluorescent probe for ferric iron. Application to iron nutrition in plant cells. J. Biol. Chem. 274:1999;13375-13383.
24. Powell L.W., George D.K., McDonnell S.M., Kowdley K.V. Diagnosis of hemochromatosis. Ann. Intern. Med. 129:1998;925-931.
25. Andrews N.C. Metal transporters and disease. Curr. Opin. Chem. Biol. 6:2002;181-186.
26. Meneghini R. Iron homeostasis, oxidative stress, and DNA damage. Free Radic. Biol. Med. 23:1997;783-792.
27. Toyokuni S. Iron-induced carcinogenesis: the role of redox regulation. Free Radic. Biol. Med. 20:1996;553-566.
28. Richmond H.G. Induction of sarcoma in the rat by iron-dextran complex. Br. Med. J. 1:1959;947-949.
29. Greenberg G. Sarcomata have developed after intramuscular injection of iron. Br. Med. J. 1:1976;1508-1509.
30. Selby J.V., Friedman G.D. Epidemiologic evidence of an association between body iron stores and risk of cancer. Int. J. Cancer. 41:1988;677-682.
31. Stevens R.G., Jones D.Y., Micozzi M.S., Taylor P.R. Body iron stores and the risk of cancer. N. Engl. J. Med. 319:1988;1047-1052.
32. Stevens R.G., Beasley R.P., Blumberg B.S. Iron-binding proteins and risk of cancer in Taiwan. J. Natl. Cancer Inst. 76:1986;605-610.
33. Graf E., Eaton J.W. Dietary suppression of colonic cancer. Fiber or phytate? Cancer. 56:1985;717-718.
34. Kazantzis G. Role of cobalt, iron, lead, manganese, mercury, platinum, selenium, and titanium in carcinogenesis. Environ. Health Perspect. 40:1981;143-161.
35. Tseng M., Sandler R.S., Greenberg E.R., Mandel J.S., Haile R.W., Baron J.A. Dietary iron and recurrence of colorectal adenomas. Cancer Epidemiol. Biomarkers Prev. 6:1997;1029-1032.
36. Kato I., Dnistrian A.M., Schwartz M., Toniolo P., Koenig K., Shore R.E., Zeleniuch-Jacquotte A., Akhmedkhanov A., Riboli E. Iron intake, body iron stores and colorectal cancer risk in women: a nested case-control study. Int. J. Cancer. 80:1999;693-698.
37. Wurzelmann J.I., Silver A., Schreinemachers D.M., Sandler R.S., Everson R.B. Iron intake and the risk of colorectal cancer. Cancer Epidemiol. Biomarkers Prev. 5:1996;503-507.
38. Bird C.L., Witte J.S., Swendseid M.E., Shikany J.M., Hunt I.F., Frankl H.D., Lee E.R., Longnecker M.P., Haile R.W. Plasma ferritin, iron intake, and the risk of colorectal polyps. Am. J. Epidemiol. 144:1996;34-41.
39. Nelson R.L. Iron and colorectal cancer risk: human studies. Nutr. Rev. 59:2001;140-148.
40. Nelson R.L., Davis F.G., Sutter E., Sobin L.H., Kikendall J.W., Bowen P. Body iron stores and risk of colonic neoplasia. J. Natl. Cancer Inst. 86:1994;455-460.
41. Herrinton L.J., Friedman G.D., Baer D., Selby J.V. Transferrin saturation and risk of cancer. Am. J. Epidemiol. 142:1995;692-698.
42. Tseng M., Greenberg E.R., Sandler R.S., Baron J.A., Haile R.W., Blumberg B.S., McGlynn K.A. Serum ferritin concentration and recurrence of colorectal adenoma. Cancer Epidemiol. Biomarkers Prev. 9:2000;625-630.
43. Nelson R.L., Davis F.G., Persky V., Becker E. Risk of neoplastic and other diseases among people with heterozygosity for hereditary hemochromatosis. Cancer. 76:1995;875-879.
44. Beckman L.E., Van Landeghem G.F., Sikstrom C., Wahlin A., Markevarn B., Hallmans G., Lenner P., Athlin L., Stenling R., Beckman L. Interaction between haemochromatosis and transferrin receptor genes in different neoplastic disorders. Carcinogenesis. 20:1999;1231-1233.
45. Fleming R.E., Sly W.S. Mechanisms of iron accumulation in hereditary hemochromatosis. Annu. Rev. Physiol. 64:2002;663-680.
46. Philpott C.C. Molecular aspects of iron absorption: insights into the role of HFE in hemochromatosis. Hepatology. 35:2002;993-1001.
47. Lund E.K., Wharf S.G., Fairweather-Tait S.J., Johnson I.T. Oral ferrous sulfate supplements increase the free radical-generating capacity of feces from healthy volunteers. Am. J. Clin. Nutr. 69:1999;250-255.
48. Lund E.K., Wharf S.G., Fairweather-Tait S.J., Johnson I.T. Increases in the concentrations of available iron in response to dietary iron supplementation are associated with changes in crypt cell proliferation in rat large intestine. J. Nutr. 128:1998;175-179.
49. Kuratko C.N. Increasing dietary lipid and iron content decreases manganese superoxide dismutase activity in colonic mucosa. Nutr. Cancer. 28:1997;36-40.
50. Lund E.K., Fairweather-Tait S.J., Wharf S.G., Johnson I.T. Chronic exposure to high levels of dietary iron fortification increases lipid peroxidation in the mucosa of the rat large intestine. J. Nutr. 131:2001;2928-2931.
51. Davis C.D., Feng Y. Dietary copper, manganese and iron affect the formation of aberrant crypts in colon of rats administered 3,2′-dimethyl- 4-aminobiphenyl. J. Nutr. 129:1999;1060-1067.
52. Liu Z., Tomotake H., Wan G., Watanabe H., Kato N. Combined effect of dietary calcium and iron on colonic aberrant crypt foci, cell proliferation and apoptosis, and fecal bile acids in 1,2-dimethylhydrazine-treated rats. Oncol. Rep. 8:2001;893-897.
53. Sesink A.L., Termont D.S., Kleibeuker J.H., Van der Meer R. Red meat and colon cancer: the cytotoxic and hyperproliferative effects of dietary heme. Cancer Res. 59:1999;5704-5709.
54. Stevens R.G., Morris J.E., Cordis G.A., Anderson L.E., Rosenberg D.W., Sasser L.B. Oxidative damage in colon and mammary tissue of the HFE-knockout mouse. Free Radic. Biol. Med. 34:2003;1212-1216.
55. Sawa T., Akaike T., Kida K., Fukushima Y., Takagi K., Maeda H. Lipid peroxyl radicals from oxidized oils and heme-iron: implication of a high-fat diet in colon carcinogenesis. Cancer Epidemiol. Biomarkers Prev. 7:1998;1007-1012.
56. Campbell S., Ghosh S. Ulcerative colitis and colon cancer: strategies for cancer prevention. Dig. Dis. 20:2002;38-48.
57. Seril D.N., Liao J., Ho K.L., Warsi A., Yang C.S., Yang G.Y. Dietary iron supplementation enhances DSS-induced colitis and associated colorectal carcinoma development in mice. Dig. Dis. Sci. 47:2002;1266-1278.
58. Seril D.N., Liao J., Ho K.L., Yang C.S., Yang G.Y. Inhibition of chronic ulcerative colitis-associated colorectal adenocarcinoma development in a murine model by N-acetylcysteine. Carcinogenesis. 23:2002;993-1001.
59. Nunez M.T., Tapia V., Toyokuni S., Okada S. Iron-induced oxidative damage in colon carcinoma (Caco-2) cells. Free Radic. Res. 34:2001;57-68.
60. Tandy S., Williams M., Leggett A., Lopez-Jimenez M., Dedes M., Ramesh B., Srai S.K., Sharp P. Nramp2 expression is associated with pH-dependent iron uptake across the apical membrane of human intestinal Caco-2 cells. J. Biol. Chem. 275:2000;1023-1029.
61. Glei M., Latunde-Dada G.O., Klinder A., Becker T.W., Hermann U., Voigt K., Pool-Zobel B.L. Iron-overload induces oxidative DNA damage in the human colon carcinoma cell line HT29 clone 19A. Mutat. Res. 519:2002;151-161.
62. Bassett M.L., Halliday J.W., Powell L.W. Value of hepatic iron measurements in early hemochromatosis and determination of the critical iron level associated with fibrosis. Hepatology. 6:1986;24-29.
63. Bonkovsky H.L. Iron and the liver. Am. J. Med. Sci. 301:1991;32-43.
64. Halliday J.W., Searle J. Hepatic iron deposition in human disease and animal models. Biometals. 9:1996;205-209.
65. Bradbear R.A., Bain C., Siskind V., Schofield F.D., Webb S., Axelsen E.M., Halliday J.W., Bassett M.L., Powell L.W. Cohort study of internal malignancy in genetic hemochromatosis and other chronic nonalcoholic liver diseases. J. Natl. Cancer Inst. 75:1985;81-84.
66. Niederau C., Fischer R., Sonnenberg A., Stremmel W., Trampisch H.J., Strohmeyer G. Survival and causes of death in cirrhotic and in noncirrhotic patients with primary hemochromatosis. N. Engl. J. Med. 313:1985;1256-1262.
67. Grando-Lemaire V., Guettier C., Chevret S., Beaugrand M., Trinchet J.C. Hepatocellular carcinoma without cirrhosis in the West: epidemiological factors and histopathology of the non-tumorous liver, Groupe d'Etude et de Traitement du Carcinome Hepatocellulaire. J. Hepatol. 31:1999;508-513.
68. Blanc J.F., Bioulac-Sage P., Balabaud C. Iron overload and cancer. Bull. Acad. Natl. Med. 184:2000;355-363.
69. Feder J.N., Gnirke A., Thomas W., Tsuchihashi Z., Ruddy D.A., Basava A., Dormishian F., Domingo R. Jr., Ellis M.C., Fullan A., Hinton L.M., Jones N.L., Kimmel B.E., Kronmal G.S., Lauer P., Lee V.K., Loeb D.B., Mapa F.A., McClelland E., Meyer N.C., Mintier G.A., Moeller N., Moore T., Morikang E., Wolff R.K.et al. A novel MHC class I-like gene is mutated in patients with hereditary haemochromatosis. Nat. Genet. 13:1996;399-408.
70. Andrews N.C., Levy J.E. Iron is hot: an update on the pathophysiology of hemochromatosis. Blood. 92:1998;1845-1851.
71. Bacon B.R., Powell L.W., Adams P.C., Kresina T.F., Hoofnagle J.H. Molecular medicine and hemochromatosis: at the crossroads. Gastroenterology. 116:1999;193-207.
72. Camaschella C., Piperno A. Hereditary hemochromatosis: recent advances in molecular genetics and clinical management. Haematologica. 82:1997;77-84.
73. Lyon E., Frank E.L. Hereditary hemochromatosis since discovery of the HFE gene. Clin. Chem. 47:2001;1147-1156.
74. Beutler E., Gelbart T., West C., Lee P., Adams M., Blackstone R., Pockros P., Kosty M., Venditti C.P., Phatak P.D., Seese N.K., Chorney K.A., Ten Elshof A.E., Gerhard G.S., Chorney M. Mutation analysis in hereditary hemochromatosis. Blood Cells Mol. Dis. 22:1996;187-194.
75. Cuthbert J.A. Iron, HFE, and hemochromatosis update. J. Invest. Med. 45:1997;518-529.
76. Roth M., Giraldo P., Hariti G., Poloni E.S., Sanchez-Mazas A., Stefano G.F., Dugoujon J.M., Coppin H. Absence of the hemochromatosis gene Cys282Tyr mutation in three ethnic groups from Algeria (Mzab), Ethiopia, and Senegal. Immunogenetics. 46:1997;222-225.
77. Bastin J.M., Jones M., O'Callaghan C.A., Schimanski L., Mason D.Y., Townsend A.R. Kupffer cell staining by an HFE-specific monoclonal antibody: implications for hereditary haemochromatosis. Br. J. Haematol. 103:1998;931-941.
78. Waheed A., Parkkila S., Zhou X.Y., Tomatsu S., Tsuchihashi Z., Feder J.N., Schatzman R.C., Britton R.S., Bacon B.R., Sly W.S. Hereditary hemochromatosis: effects of C282Y and H63D mutations on association with beta2-microglobulin, intracellular processing, and cell surface expression of the HFE protein in COS-7 cells. Proc. Natl. Acad. Sci. U.S.A. 94:1997;12384-12389.
79. Waheed A., Grubb J.H., Zhou X.Y., Tomatsu S., Fleming R.E., Costaldi M.E., Britton R.S., Bacon B.R., Sly W.S. Regulation of transferrin-mediated iron uptake by HFE, the protein defective in hereditary hemochromatosis. Proc. Natl. Acad. Sci. U.S.A. 99:2002;3117-3122.
80. Hanson E.H., Imperatore G., Burke W. HFE gene and hereditary hemochromatosis: a HuGE review. Human genome epidemiology. Am. J. Epidemiol. 154:2001;193-206.
81. Yang Q., McDonnell S.M., Khoury M.J., Cono J., Parrish R.G. Hemochromatosis-associated mortality in the United States from 1979 to 1992: an analysis of Multiple-Cause Mortality Data. Ann. Intern. Med. 129:1998;946-953.
82. Lauret E., Rodriguez M., Gonzalez S., Linares A., Lopez-Vazquez A., Martinez-Borra J., Rodrigo L., Lopez-Larrea C. HFE gene mutations in alcoholic and virus-related cirrhotic patients with hepatocellular carcinoma. Am. J. Gastroenterol. 97:2002;1016-1021.
83. Milman N., Pedersen P., a Steig T., Byg K.E., Graudal N., Fenger K. Clinically overt hereditary hemochromatosis in Denmark 1948-1985: epidemiology, factors of significance for long-term survival, and causes of death in 179 patients. Ann. Hematol. 80:2001;737-744.
84. Niederau C., Fischer R., Purschel A., Stremmel W., Haussinger D., Strohmeyer G. Long-term survival in patients with hereditary hemochromatosis. Gastroenterology. 110:1996;1107-1119.
85. Gordeuk V.R., McLaren C.E., MacPhail A.P., Deichsel G., Bothwell T.H. Associations of iron overload in Africa with hepatocellular carcinoma and tuberculosis: Strachan's 1929 thesis revisited. Blood. 87:1996;3470-3476.
86. Moyo V.M., Makunike R., Gangaidzo I.T., Gordeuk V.R., McLaren C.E., Khumalo H., Saungweme T., Rouault T., Kiire C.F. African iron overload and hepatocellular carcinoma (HA-7-0-080). Eur. J. Haematol. 60:1998;28-34.
87. Mandishona E., MacPhail A.P., Gordeuk V.R., Kedda M.A., Paterson A.C., Rouault T.A., Kew M.C. Dietary iron overload as a risk factor for hepatocellular carcinoma in Black Africans. Hepatology. 27:1998;1563-1566.
88. Bahram S., Gilfillan S., Kuhn L.C., Moret R., Schulze J.B., Lebeau A., Schumann K. Experimental hemochromatosis due to MHC class I HFE deficiency: immune status and iron metabolism. Proc. Natl. Acad. Sci. U.S.A. 96:1999;13312-13317.
89. Levy J.E., Montross L.K., Cohen D.E., Fleming M.D., Andrews N.C. The C282Y mutation causing hereditary hemochromatosis does not produce a null allele. Blood. 94:1999;9-11.
90. Zhou X.Y., Tomatsu S., Fleming R.E., Parkkila S., Waheed A., Jiang J., Fei Y., Brunt E.M., Ruddy D.A., Prass C.E., Schatzman R.C., O'Neill R., Britton R.S., Bacon B.R., Sly W.S. HFE gene knockout produces mouse model of hereditary hemochromatosis. Proc. Natl. Acad. Sci. U.S.A. 95:1998;2492-2497.
91. M.E. Horvath, S.P. Faux, A. Blazovics, J. Feher, Lipid and DNA oxidative damage in experimentally induced hepatic porphyria in C57BL/10ScSn mice, Z. Gastroenterol. 39 (2001) 453-455, 458.
92. Carthew P., Nolan B.M., Smith A.G., Edwards R.E. Iron promotes DEN initiated GST-P foci in rat liver. Carcinogenesis. 18:1997;599-603.
93. Wang G.S., Eriksson L.C., Xia L., Olsson J., Stal P. Dietary iron overload inhibits carbon tetrachloride-induced promotion in chemical hepatocarcinogenesis: effects on cell proliferation, apoptosis, and antioxidation. J. Hepatol. 30:1999;689-698.
94. Stal P., Wang G.S., Olsson J.M., Eriksson L.C. Effects of dietary iron overload on progression in chemical hepatocarcinogenesis. Liver. 19:1999;326-334.
95. Lemmer E.R., Gelderblom W.C., Shephard E.G., Abel S., Seymour B.L., Cruse J.P., Kirsch R.E., Marasas W.F., Hall P.M. The effects of dietary iron overload on fumonisin B1-induced cancer promotion in the rat liver. Cancer Lett. 146:1999;207-215.
96. Davies R., Clothier B., Smith A.G. Mutation frequency in the lacI gene of liver DNA from lambda/lacI transgenic mice following the interaction of PCBs with iron causing hepatic cancer and porphyria. Mutagenesis. 15:2000;379-383.
97. Whysner J., Wang C.X. Hepatocellular iron accumulation and increased cell proliferation in polychlorinated biphenyl-exposed Sprague-Dawley rats and the development of hepatocarcinogenesis. Toxicol. Sci. 62:2001;36-45.
98. Stal P., Hultcrantz R., Moller L., Eriksson L.C. The effects of dietary iron on initiation and promotion in chemical hepatocarcinogenesis. Hepatology. 21:1995;521-528.
99. Pesch B., Haerting J., Ranft U., Klimpel A., Oelschlagel B., Schill W. Occupational risk factors for renal cell carcinoma: agent-specific results from a case-control study in Germany. MURC Study Group. Multicenter urothelial and renal cancer study. Int. J. Epidemiol. 29:2000;1014-1024.
100. Parent M.E., Hua Y., Siemiatycki J. Occupational risk factors for renal cell carcinoma in Montreal. Am. J. Ind. Med. 38:2000;609-618.
101. Mandel J.S., McLaughlin J.K., Schlehofer B., Mellemgaard A., Helmert U., Lindblad P., McCredie M., Adami H.O. International renal-cell cancer study. IV. Occupation. Int. J. Cancer. 61:1995;601-605.
102. McCredie M., Stewart J.H. Risk factors for kidney cancer in New South Wales. IV. Occupation. Br. J. Ind. Med. 50:1993;349-354.
103. Partanen T., Heikkila P., Hernberg S., Kauppinen T., Moneta G., Ojajarvi A. Renal cell cancer and occupational exposure to chemical agents. Scand. J. Work Environ. Health. 17:1991;231-239.
104. Okada S. Prevention of free-radical mediated tissue damage and carcinogenesis induced by low-molecular-weight iron. Biometals. 16:2003;99-101.
105. Toyokuni S., Luo X.P., Tanaka T., Uchida K., Hiai H., Lehotay D.C. Induction of a wide range of C(2-12) aldehydes and C(7-12) acyloins in the kidney of Wistar rats after treatment with a renal carcinogen, ferric nitrilotriacetate. Free Radic. Biol. Med. 22:1997;1019-1027.
106. Tanaka T., Nishiyama Y., Okada K., Satoh K., Fukuda A., Uchida K., Osawa T., Hiai H., Toyokuni S. Over-expression of glutathione S-transferase Yp isozyme and concomitant down-regulation of Ya isozyme in renal cell carcinoma of rats induced by ferric nitrilotriacetate. Carcinogenesis. 19:1998;897-903.
107. Fukuda A., Osawa T., Oda H., Toyokuni S., Satoh K., Uchida K. Oxidative stress response in iron-induced renal carcinogenesis: acute nephrotoxicity mediates the enhanced expression of glutathione S-transferase Yp isozyme. Arch. Biochem. Biophys. 329:1996;39-46.
108. Toyokuni S., Tanaka T., Nishiyama Y., Okamoto K., Nakashima Y., Hamazaki S., Okada S., Hiai H. Induction of renal cell carcinoma in male Wistar rats treated with cupric nitrilotriacetate. Lab. Invest. 75:1996;239-248.
109. Akiyama T., Hamazaki S., Okada S. Absence of ras mutations and low incidence of p53 mutations in renal cell carcinomas induced by ferric nitrilotriacetate. Jpn. J. Cancer Res. 86:1995;1143-1149.
110. Nishiyama Y., Suwa H., Okamoto K., Fukumoto M., Hiai H., Toyokuni S. Low incidence of point mutations in H-, K- and N-ras oncogenes and p53 tumor suppressor gene in renal cell carcinoma and peritoneal mesothelioma of Wistar rats induced by ferric nitrilotriacetate. Jpn. J. Cancer Res. 86:1995;1150-1158.
111. Hiroyasu M., Ozeki M., Kohda H., Echizenya M., Tanaka T., Hiai H., Toyokuni S. Specific allelic loss of p16 (INK4A) tumor suppressor gene after weeks of iron-mediated oxidative damage during rat renal carcinogenesis. Am. J. Pathol. 160:2002;419-424.
112. Toyokuni S. Iron and carcinogenesis: from Fenton reaction to target genes. Redox. Rep. 7:2002;189-197.
113. Wyllie S., Liehr J.G. Enhancement of estrogen-induced renal tumorigenesis in hamsters by dietary iron. Carcinogenesis. 19:1998;1285-1290.
114. Vyhlidal C., Li X., Safe S. Estrogen regulation of transferrin gene expression in MCF-7 human breast cancer cells. J. Mol. Endocrinol. 29:2002;305-317.
115. Wyllie S., Liehr J.G. Release of iron from ferritin storage by redox cycling of stilbene and steroid estrogen metabolites: a mechanism of induction of free radical damage by estrogen. Arch. Biochem. Biophys. 346:1997;180-186.
116. Liehr J.G., Jones J.S. Role of iron in estrogen-induced cancer. Curr. Med. Chem. 8:2001;839-849.
117. Tossavainen A. Estimated risk of lung cancer attributable to occupational exposures in iron and steel foundries. IARC Sci. Publ. 104:1990;363-367.
118. Weinberg E.D. The development of awareness of the carcinogenic hazard of inhaled iron. Oncol. Res. 11:1999;109-113.
119. Rodriguez V., Tardon A., Kogevinas M., Prieto C.S., Cueto A., Garcia M., Menendez I.A., Zaplana J. Lung cancer risk in iron and steel foundry workers: a nested case control study in Asturias, Spain. Am. J. Ind. Med. 38:2000;644-650.
120. Xu Z., Pan G.W., Liu L.M., Brown L.M., Guan D.X., Xiu Q., Sheng J.H., Stone B.J., Dosemeci M., Fraumeni J.F. Jr., Blot W.J. Cancer risks among iron and steel workers in Anshan, China. Part I. Proportional mortality ratio analysis. Am. J. Ind. Med. 30:1996;1-6.
121. Xu Z., Brown L.M., Pan G.W., Liu T.F., Gao G.S., Stone B.J., Cao R.M., Guan D.X., Sheng J.H., Yan Z.S., Dosemeci M., Fraumeni J.F. Jr., Blot W.J. Cancer risks among iron and steel workers in Anshan, China. Part II. Case-control studies of lung and stomach cancer. Am. J. Ind. Med. 30:1996;7-15.
122. Chen S.Y., Hayes R.B., Liang S.R., Li Q.G., Stewart P.A., Blair A. Mortality experience of haematite mine workers in China. Br. J. Ind. Med. 47:1990;175-181.
123. Chau N., Benamghar L., Pham Q.T., Teculescu D., Rebstock E., Mur J.M. Mortality of iron miners in Lorraine (France): relations between lung function and respiratory symptoms and subsequent mortality. Br. J. Ind. Med. 50:1993;1017-1031.
124. Pham Q.T., Chau N., Patris A., Trombert B., Henquel J.C., Geny M., Teculescu D. Prospective mortality study among iron miners. Cancer Detect. Prev. 15:1991;449-454.
125. Pham Q.T., Teculescu D., Bruant A., Chau N., Viaggi M.N., Rebstock E. Iron miners - a 10 year follow-up. Eur. J. Epidemiol. 8:1992;594-600.
126. Moulin J.J., Clavel T., Roy D., Dananche B., Marquis N., Fevotte J., Fontana J.M. Risk of lung cancer in workers producing stainless steel and metallic alloys. Int. Arch. Occup. Environ Health. 73:2000;171-180.
127. Andjelkovich D.A., Shy C.M., Brown M.H., Janszen D.B., Levine R.J., Richardson R.B. Mortality of iron foundry workers. III. Lung cancer case-control study. J. Occup. Med. 36:1994;1301-1309.
128. Costa D., Guignard J., Zalma R., Pezerat H. Production of free radicals arising from the surface activity of minerals and oxygen. Part I. Iron mine ores. Toxicol. Ind. Health. 5:1989;1061-1078.
129. Costa D., Guignard J., Pezerat H. Production of free radicals arising from the surface activity of minerals and oxygen. Part II. Arsenides, sulfides, and sulfoarsenides of iron, nickel, and copper. Toxicol. Ind. Health. 5:1989;1079-1097.
130. Ghio A.J., Kennedy T.P., Whorton A.R., Crumbliss A.L., Hatch G.E., Hoidal J.R. Role of surface complexed iron in oxidant generation and lung inflammation induced by silicates. Am. J. Physiol. 263:1992;L511-L518.
131. Fang R., Aust A.E. Induction of ferritin synthesis in human lung epithelial cells treated with crocidolite asbestos. Arch. Biochem. Biophys. 340:1997;369-375.
132. Huang X., Laurent P.A., Zalma R., Pezerat H. Inactivation of alpha 1-antitrypsin by aqueous coal solutions: possible relation to the emphysema of coal workers. Chem. Res. Toxicol. 6:1993;452-458.
133. 2+ content: possible role in coal workers' pneumoconiosis. Chem. Res. Toxicol. 11:1998;722-729.
134. Smith K.R., Aust A.E. Mobilization of iron from urban particulates leads to generation of reactive oxygen species in vitro and induction of ferritin synthesis in human lung epithelial cells. Chem. Res. Toxicol. 10:1997;828-834.
135. Smith K.R., Veranth J.M., Lighty J.S., Aust A.E. Mobilization of iron from coal fly ash was dependent upon the particle size and the source of coal. Chem. Res. Toxicol. 11:1998;1494-1500.
136. Zhang Q., Dai J., Ali A., Chen L., Huang X. Roles of bioavailable iron and calcium in coal dust-induced oxidative stress: possible implications in coal workers' lung disease. Free Radic. Res. 36:2002;285-294.
137. Elias Z., Poirot O., Schneider O., Marande A.M., Daniere M.C., Terzetti F., Pezerat H., Fournier J., Zalma R. Cytotoxic and transforming effects of some iron-containing minerals in Syrian hamster embryo cells. Cancer Detect Prev. 19:1995;405-414.
138. Bhasin G., Kausar H., Sarwar Alam M., Athar M. Progressive iron overload enhances chemically mediated tumor promotion in murine skin. Arch. Biochem. Biophys. 409:2003;262-273.
139. Bhasin G., Kauser H., Athar M. Low iron state is associated with reduced tumor promotion in a two-stage mouse skin carcinogenesis model. Food Chem. Toxicol. 40:2002;1105-1111.
140. Diwan B.A., Kasprzak K.S., Anderson L.M. Promotion of dimethylbenz[a]anthracene-initiated mammary carcinogenesis by iron in female Sprague-Dawley rats. Carcinogenesis. 18:1997;1757-1762.
141. Goldstein S.R., Yang G.Y., Chen X., Curtis S.K., Yang C.S. Studies of iron deposits, inducible nitric oxide synthase and nitrotyrosine in a rat model for esophageal adenocarcinoma. Carcinogenesis. 19:1998;1445-1449.
142. Balla G., Jacob H.S., Balla J., Rosenberg M., Nath K., Apple F., Eaton J.W., Vercellotti G.M. Ferritin: a cytoprotective antioxidant strategem of endothelium. J. Biol. Chem. 267:1992;18148-18153.
143. Harrison P.M., Arosio P. The ferritins: molecular properties, iron storage function and cellular regulation. Biochim. Biophys. Acta. 1275:1996;161-203.
144. Torti F.M., Torti S.V. Regulation of ferritin genes and protein. Blood. 99:2002;3505-3516.
145. Miyata Y., Koga S., Nishikido M., Noguchi M., Kanda S., Hayashi T., Saito Y., Kanetake H. Predictive values of acute phase reactants, basic fetoprotein, and immunosuppressive acidic protein for staging and survival in renal cell carcinoma. Urology. 58:2001;161-164.
146. Ozen H., Uygur C., Sahin A., Tekgul S., Ergen A., Remzi D. Clinical significance of serum ferritin in patients with renal cell carcinoma. Urology. 46:1995;494-498.
147. Partin A.W., Criley S.R., Steiner M.S., Hsieh K., Simons J.W., Lumadue J., Carter H.B., Marshall F.F. Serum ferritin as a clinical marker for renal cell carcinoma: influence of tumor volume. Urology. 45:1995;211-217.
148. Kirkali Z., Esen A.A., Kirkali G., Guner G. Ferritin: a tumor marker expressed by renal cell carcinoma. Eur. Urol. 28:1995;131-134.
149. Akiba S., Neriishi K., Blot W.J., Kabuto M., Stevens R.G., Kato H., Land C.E. Serum ferritin and stomach cancer risk among a Japanese population. Cancer. 67:1991;1707-1712.
150. Ali M.A., Akhmedkhanov A., Zeleniuch-Jaquotte A., Toniolo P., Frenkel K., Huang X. Reliability of serum iron, ferritin, nitrite, and association with risk of renal cancer in women. Cancer Detect. Prev. 27:2003;116-121.
151. Yang D.C., Jiang X.P., Elliott R.L., Head J.F. Inhibition of growth of human breast carcinoma cells by an antisense oligonucleotide targeted to the transferrin receptor gene. Anticancer Res. 21:2001;1777-1787.
152. Kemp J.D., Cardillo T., Stewart B.C., Kehrberg E., Weiner G., Hedlund B., Naumann P.W. Inhibition of lymphoma growth in vivo by combined treatment with hydroxyethyl starch deferoxamine conjugate and IgG monoclonal antibodies against the transferrin receptor. Cancer Res. 55:1995;3817-3824.
153. Kemp J.D., Smith K.M., Mayer J.M., Gomez F., Thorson J.A., Naumann P.W. Effects of anti-transferrin receptor antibodies on the growth of neoplastic cells. Pathobiology. 60:1992;27-32.
154. Buss J.L., Torti F.M., Torti S.V. The role of iron chelation in cancer therapy. Curr. Med. Chem. 10:2003;1021-1034.
155. Lovejoy D.B., Richardson D.R. Iron chelators as anti-neoplastic agents: current developments and promise of the PIH class of chelators. Curr. Med. Chem. 10:2003;1035-1049.
156. Hann H.W., Stahlhut M.W., Rubin R., Maddrey W.C. Antitumor effect of deferoxamine on human hepatocellular carcinoma growing in athymic nude mice. Cancer. 70:1992;2051-2056.
157. Simonart T., Boelaert J.R., Mosselmans R., Andrei G., Noel J.C., Clercq E.D., Snoeck R. Antiproliferative and apoptotic effects of iron chelators on human cervical carcinoma cells. Gynecol. Oncol. 85:2002;95-102.
158. Simonart T., Boelaert J.R., Andrei G., Clercq E.D., Snoeck R. Iron withdrawal strategies fail to prevent the growth of SiHa-induced tumors in mice. Gynecol. Oncol. 90:2003;91-95.
159. Donfrancesco A., Deb G., Dominici C., Pileggi D., Castello M.A., Helson L. Effects of a single course of deferoxamine in neuroblastoma patients. Cancer Res. 50:1990;4929-4930.
160. Torti S.V., Buss J.L., Torti F.M. The role of iron chelation in cancer therapy. Curr. Med. Chem. 10:2003;1021-1034.
161. K. Frenkel, Carcinogenesis: role of reactive oxygen and nitrogen species, in: J. Bertino (Ed.), Encyclopedia of Cancer, Elsevier, New York, 2002, pp. 359-367.
162. Liochev S.I., Fridovich I. The Haber-Weiss cycle - 70 years later: an alternative view. Redox Rep. 7:2002;55-57. (author reply 59-60).
163. Koppenol W.H. The Haber-Weiss cycle - 70 years later. Redox. Rep. 6:2001;229-234.
164. A. Boveris, E. Cadenas, Cellular Sources and Steady-state Levels of Reactive Oxygen Species, Marcel Dekker, New York, 1997.
165. Jones D.P. Intracellular diffusion gradients of O2 and ATP. Am. J. Physiol. 250:1986;C663-C675.
166. Qian S.Y., Buettner G.R. Iron and dioxygen chemistry is an important route to initiation of biological free radical oxidations: an electron paramagnetic resonance spin trapping study. Free Radic. Biol. Med. 26:1999;1447-1456.
167. Kachur A.V., Tuttle S.W., Biaglow J.E. Autoxidation of ferrous ion complexes: a method for the generation of hydroxyl radicals. Radiat. Res. 150:1998;475-482.
168. Huang X., Dai J., Fournier J., Ali A.M., Zhang Q., Frenkel K. Ferrous ion autoxidation and its chelation in iron-loaded human liver HepG2 cells. Free Radic. Biol. Med. 32:2002;84-92.
169. Oosthuizen M.M., Greyling D. Hydroxyl radical generation: the effect of bicarbonate, dioxygen and buffer concentration on pH-dependent chemiluminescence. Redox. Rep. 6:2001;105-116.
170. Wink D.A., Nims R.W., Saavedra J.E., Utermahlen W.E. Jr., Ford P.C. The Fenton oxidation mechanism: reactivities of biologically relevant substrates with two oxidizing intermediates differ from those predicted for the hydroxyl radical. Proc. Natl. Acad. Sci. U.S.A. 91:1994;6604-6608.
171. Koppenol W.H., Liebman J.F. The oxidizing nature of hydroxyl radical - a comparison with the ferryl ion. J. Phys. Chem. 88:1984;99-105.
172. Stumm W., Lee G.F. Oxygenation of ferrous iron. Ind. Eng. Chem. 53:1961;143-146.
173. Singer P., Stumm W. Acidic mine drainage: the rate-determining step. Science. 167:1969;1121-1123.
174. Lowson R.T. Aqueous oxidation of pyrite by molecule of oxygen. Chem. Rev. 82:1982;461-497.
175. Godden D.J., Kerr K.M., Watt S.J., Legge J.S. Iron lung: bronchoscopic and pathological consequences of aspiration of ferrous sulphate. Thorax. 46:1991;142-143.
176. Mizuki M., Onizuka O., Aoki T., Tsuda T. A case of remarkable bronchial stenosis due to aspiration of delayed-release iron tablet. Nihon Kyobu Shikkan Gakkai Zasshi. 27:1989;234-239.
177. Tarkka M., Anttila S., Sutinen S. Bronchial stenosis after aspiration of an iron tablet. Chest. 93:1988;439-441.
178. Huang X., Zalma R., Pezerat H. Factors that influence the formation and stability of hydrated ferrous sulfate in coal dusts. Possible relation to the emphysema of coal miners. Chem. Res. Toxicol. 7:1994;451-457.
179. Schafer F.Q., Buettner G.R. Acidic pH amplifies iron-mediated lipid peroxidation in cells. Free Radic. Biol. Med. 28:2000;1175-1181.
180. Nyberg K., Johansson U., Rundquist I., Camner P. Estimation of pH in individual alveolar macrophage phagolysosomes. Exp. Lung Res. 15:1989;499-510.
181. Eaton J.W., Qian M. Molecular bases of cellular iron toxicity. Free Radic. Biol. Med. 32:2002;833-840.
182. Garner B., Roberg K., Brunk U.T. Endogenous ferritin protects cells with iron-laden lysosomes against oxidative stress. Free Radic. Res. 29:1998;103-114.
183. Wike-Hooley J.L., Haveman J., Reinhold H.S. The relevance of tumour pH to the treatment of malignant disease. Radiother. Oncol. 2:1984;343-366.
184. Kawanishi S., Hiraku Y., Murata M., Oikawa S. The role of metals in site-specific DNA damage with reference to carcinogenesis. Free Radic. Biol. Med. 32:2002;822-832.
185. Kakhlon O., Cabantchik Z.I. The labile iron pool: characterization, measurement, and participation in cellular processes. 1. Free Radic. Biol. Med. 33:2002;1037-1046.
186. Hu W., Feng Z., Eveleigh J., Iyer G., Pan J., Amin S., Chung F.L., Tang M.S. The major lipid peroxidation product, trans-4-hydroxy-2-nonenal, preferentially forms DNA adducts at codon 249 of human p53 gene, a unique mutational hotspot in hepatocellular carcinoma. Carcinogenesis. 23:2002;1781-1789.
187. Marrogi A.J., Khan M.A., van Gijssel H.E., Welsh J.A., Rahim H., Demetris A.J., Kowdley K.V., Hussain S.P., Nair J., Bartsch H., Okby N., Poirier M.C., Ishak K.G., Harris C.C. Oxidative stress and p53 mutations in the carcinogenesis of iron overload-associated hepatocellular carcinoma. J. Natl. Cancer Inst. 93:2001;1652-1655.
188. Hussain S.P., Raja K., Amstad P.A., Sawyer M., Trudel L.J., Wogan G.N., Hofseth L.J., Shields P.G., Billiar T.R., Trautwein C., Hohler T., Galle P.R., Phillips D.H., Markin R., Marrogi A.J., Harris C.C. Increased p53 mutation load in nontumorous human liver of Wilson disease and hemochromatosis: oxyradical overload diseases. Proc. Natl. Acad. Sci. U.S.A. 97:2000;12770-12775.
189. Angel P., Karin M. The role of Jun, Fos and the AP-1 complex in cell-proliferation and transformation. Biochim. Biophys. Acta. 1072:1991;129-157.
190. K. Kelly, Y. Chu, The regulation of MAP kinase pathways by MAP kinase phosphatases, in: J.S. Gutkind (Ed.), Signaling Networks and Cell Cycle Control, Human Press, Totowa, 2000, pp. 165-182.
191. J. Dai, C. Huang, J. Wu, C. Yang, K. Frenkel, X. Huang, Iron-induced interleukin-6 gene expression: possible mediation through the extracellular signal-regulated kinase and p38 mitogen-activated protein kinase pathways, BioMetals (2004) in press.
192. Huang C., Li J., Zhang Q., Huang X. Role of bioavailable iron in coal dust-induced activation of activator protein-1 and nuclear factor of activated t cells: difference between Pennsylvania and Utah coal dusts. Am. J. Respir. Cell. Mol. Biol. 27:2002;568-574.
193. Huang X., Zhang Q. Coal-induced interleukin-6 gene expression is mediated through ERKs and p38 MAPK pathways. Toxicol. Appl. Pharmacol. 191:2003;40-47.
194. T. Hirano, Interleukin-6, in: A. Thomson (Ed.), The Cytokine Handbook, third ed., Academic Press, New York, 1998, pp. 197-228.
195. Coussens L.M., Werb Z. Inflammation and cancer. Nature. 420:2002;860-867.
196. Tsukamoto H. Iron regulation of hepatic macrophage TNFalpha expression(1,2). Free Radic. Biol. Med. 32:2002;309-313.
197. Maxwell P.H., Ratcliffe P.J. Oxygen sensors and angiogenesis. Semin. Cell Dev. Biol. 13:2002;29-37.
198. Tacchini L., Bianchi L., Bernelli-Zazzera A., Cairo G. Transferrin receptor induction by hypoxia. HIF-1-mediated transcriptional activation and cell-specific post-transcriptional regulation. J. Biol. Chem. 274:1999;24142-24146.
199. Hanson E.S., Leibold E.A. Regulation of iron regulatory protein 1 during hypoxia and hypoxia/reoxygenation. J. Biol. Chem. 273:1998;7588-7593.
200. Choi K.S., Bae M.K., Jeong J.W., Moon H.E., Kim K.W. Hypoxia-induced angiogenesis during carcinogenesis. J. Biochem. Mol. Biol. 36:2003;120-127.
201. Pugh C.W., Ratcliffe P.J. The von Hippel-Lindau tumor suppressor. Semin. Cancer Biol. 13:2003;83-89.
202. An W.G., Kanekal M., Simon M.C., Maltepe E., Blagosklonny M.V., Neckers L.M. Stabilization of wild-type p53 by hypoxia-inducible factor 1alpha. Nature. 392:1998;405-408.
203. 2-regulated prolyl hydroxylation. Science. 292:2001;468-472.
204. 2 sensing. Science. 292:2001;464-468.
205. Le N.T., Richardson D.R. The role of iron in cell cycle progression and the proliferation of neoplastic cells. Biochim. Biophys. Acta. 1603:2002;31-46.
206. Weinberg J.B., Hibbs J.B. Jr. Endocytosis of red blood cells or haemoglobin by activated macrophages inhibits their tumoricidal effect. Nature. 269:1977;245-247.
207. Weinberg E.D. Iron withholding: a defense against viral infections. Biometals. 9:1996;393-399.
208. Weinberg E.D. Microbial pathogens with impaired ability to acquire host iron. Biometals. 13:2000;85-89.
209. Weiss G. Iron and immunity: a double-edged sword. Eur. J. Clin. Invest. 32(Suppl 1):2002;70-78.
210. Weinberg E.D. Modulation of intramacrophage iron metabolism during microbial cell invasion. Microbes Infect. 2:2000;85-89.
211. Walker E.M. Jr., Walker S.M. Effects of iron overload on the immune system. Ann. Clin. Lab. Sci. 30:2000;354-365.
212. Sunder-Plassmann G., Patruta S.I., Horl W.H. Pathobiology of the role of iron in infection. Am. J. Kidney Dis. 34:1999;S25-S29.
213. Brock J.H., Mulero V. Cellular and molecular aspects of iron and immune function. Proc. Nutr. Soc. 59:2000;537-540.
214. Worwood M. The laboratory assessment of iron status - an update. Clin. Chim. Acta. 259:1997;3-23.
215. Leggett B.A., Brown N.N., Bryant S.J., Duplock L., Powell L.W., Halliday J.W. Factors affecting the concentrations of ferritin in serum in a healthy Australian population. Clin. Chem. 36:1990;1350-1355.
216. Epsztejn S., Kakhlon O., Glickstein H., Breuer W., Cabantchik I. Fluorescence analysis of the labile iron pool of mammalian cells. Anal. Biochem. 248:1997;31-40.
217. Ali A.M., Zhang Q., Dai J., Huang X. Calcein as a fluorescent iron chemosensor for the determination of low molecular weight iron in biological fluids. Biol. Met. 16:2003;285-293.
218. Gosriwatana I., Loreal O., Lu S., Brissot P., Porter J., Hider R.C. Quantification of non-transferrin-bound iron in the presence of unsaturated transferrin. Anal. Biochem. 273:1999;212-220.
219. Breuer W., Ronson A., Slotki I.N., Abramov A., Hershko C., Cabantchik Z.I. The assessment of serum nontransferrin-bound iron in chelation therapy and iron supplementation. Blood. 95:2000;2975-2982.
220. Everse J., Hsia N. The toxicities of native and modified hemoglobins. Free Radic. Biol. Med. 22:1997;1075-1099.
221. Delanghe J.R., Langlois M.R. Hemopexin: a review of biological aspects and the role in laboratory medicine. Clin. Chim. Acta. 312:2001;13-23.
222. Paoli M., Marles-Wright J., Smith A. Structure-function relationships in heme-proteins. DNA Cell Biol. 21:2002;271-280.
223. Tolosano E., Altruda F. Hemopexin: structure, function, and regulation. DNA Cell Biol. 21:2002;297-306.