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Redox Report
Communications in Free Radical Research
Volume 7, 2002 - Issue 4
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Iron and carcinogenesis: from Fenton reaction to target genes

Shinya ToyokuniDepartment of Pathology and Biology of Diseases Graduate School of Medicine, Kyoto University, Kyoto , Japan
Pages 189-197 | Published online: 19 Jul 2013

  • Wriggleworth JM, Baum H. The biochemical function of iron. In: Jacobs A, Worwood M. (eds) Iron in Biochemistry and Medicine, II. London: Academic Press, 1980; 29–86.
  • Toyokuni S. Iron-induced carcinogenesis: the role of redox regulation. Free Radic Biol Med 1996; 20: 553–566.
  • Fenton HJH. Oxidation of tartaric acid in presence of iron. J Chem Soc 1894; 65: 899–910.
  • Gutteridge JMC, Rowley DA, Halliwell B. Superoxide-dependent formation of hydroxyl radicals and lipid peroxidation in the presence of iron salts: detection of ‘catalytic’ iron and anti-oxidant activity in extracellular fluids. Biochem J 1982; 206: 605–609.
  • Thauer R, Jungermann K, Decker K. Energy conservation in chemotrophic anaerobic bacteria. Bacteriol Rev 1977; 41: 100–180.
  • Lippard SJ, Berg JM. Principles of Bioorganic Chemistry. Mill Valley, CA: University Science Books, 1994.
  • Gutteridge JMC. Superoxide-dependent formation of hydroxyl radicals from ferric-complexes and hydrogen peroxide: an evaluation of fourteen iron chelators. Free Radic Res Commun 1990; 9: 119–125.
  • Graf E, Mahoney JR, Bryant RG, Eaton JW. Iron-catalyzed hydroxyl radical formation: stringent requirement for free iron coordination site. J Biol Chem 1984; 259: 3620–3624.
  • Toyokuni S, Sagripanti JL. Iron-mediated DNA damage: sensitive detection of DNA strand breakage catalyzed by iron. J Inorg Biochem 1992;47: 241–248.
  • Geisser P. Iron Therapy: With Special Emphasis on Oxidative Stress. Stuttgart: Georg Thieme, 1996.
  • Mulligan M, Althaus B, Linder MC. Non-ferritin, non-heme iron pools in rat tissues. Int J Biochem 1986; 18: 791–798.
  • Weaver J, Pollack S. Low-Mr iron isolated from guinea pig reticulocytes as AMP-Fe and ADP-Fe complexes. Biochem J 1989; 261: 787–792.
  • Hershko C, Peto TEA. Annotation: non-transferrin plasma iron. Br J Haematol 1987;66: 149–151.
  • Reynolds LG, Klein M. Iron-poisoning: a preventable hazard of childhood. S Afr Med J1985; 67: 680-683.
  • Buchannan WM. Shock in Bantu siderosis. Am J Clin Pathol 1971;55: 401–406.
  • Chevion M. A site-specific mechanism for free radical induced biological damage: the essential role of redox-active transition metals. Free Radic Biol Med 1988; 5: 27–37.
  • van Bockxmeer F, Morgan E. Identification of transferrin receptors in reticulocytes. Biochim Biophys Acta 1977; 468: 437–450.
  • van Bockxmeer F, Morgan E. Comparative aspects of transferrin-reticulocyte interactions: membrane receptors and iron uptake. Comp Biochem Physiol A 1982; 71: 211–218.
  • Ponka P, Beaumont C, Richardson D. Function and regulation of transferrin and ferritin. Semin Hematol 1998;35: 35–54.
  • Testa U, Pelosi E, Peschle C. The transferrin receptor. Crit Rev Oncol 1993;4: 241–276.
  • Richardson D, Ponka P. The molecular mechanisms of the metabolism and transport of iron in normal and neoplastic cells. Biochim Biophys Acta 1997; 1331: 1–40.
  • Kawabata H, Yang R, Hirama T et al. Molecular cloning of transferrin receptor 2. A new member of the transferrin receptor-like family. J Biol Chem 1999; 274: 20826–20832.
  • Fleming M, Trenor CR, Su M et al. Microcytic anaemia mice have a mutation in Nramp2, a candidate iron transporter gene. Nat Genet 1997; 16: 383–386.
  • Vidal S, Malo D, Vogan K, Skamene E, Gros P. Natural resistance to infection with intracellular parasites: isolation of a candidate for Bcg. Cell 1993;73: 469–485.
  • Gunshin H, Mackenzie B, Berger U et al. Cloning and characterization of a mammalian proton-coupled metal-ion transporter. Nature 1997; 388:482–488.
  • Gruenheid S, Pinner E, Desjardins M, Gros P. Natural resistance to infection with intracellular pathogens: the Nrampl protein is recruited to the membrane of the phagosome. J Exp Med 1997; 185: 717–730.
  • Atkinson P, Barton C. Ectopic expression of Nrampl in COS-1 cells modulates iron accumulation. FEBS Lett 1998; 425: 239–242.
  • Vulpe C, Kuo Y, Murphy T et al. Hephaestin, a ceruloplasmin homologue implicated in intestinal iron transport, is defective in the sla mouse. Nat Genet 1999; 21: 195–199.
  • McKie A, Marciani P, Rolfs A et al. A novel duodenal iron-regulated transporter, IREG1, implicated in the basolateral transfer of iron to the circulation. Mol Cell 2000; 5: 299–309.
  • Donovan A, Brownlie A, Zhou Y et al. Positional cloning of zebrafish ferroportin 1 identifies a conserved vertebrate iron exporter. Nature 2000; 403: 776–781.
  • Abboud S, Haile D. A novel mammalian iron-regulated protein involved in intracellular iron metabolism. J Biol Chem 2000; 275: 19906–19912.
  • Gurgueira S, Meneghini R. An ATP-dependent iron transport system in isolated rat liver nuclei. J Biol Chem 1996; 271: 13616–13620.
  • Babcock M, de Silva D, Oaks R et al. Regulation of mitochondrial iron accumulation by Yfhlp, a putative homolog of frataxin. Science 1997;276: 1709–1712.
  • Foury F, Cazzalini 0. Deletion of the yeast homologue of the human gene associated with Friedreich's ataxia elicits iron accumulation in mitochondria. FEBS Lett 1997;411: 373–377.
  • Becker E, Richardson D. Frataxin: its role in iron metabolism and the pathogenesis of Friedreich's ataxia. Int J Biochem Cell Biol 2001;33: 1–10.
  • Richardson D, Mouralian C, Ponka P, Becker E. Development of potential iron chelators for the treatment of Friedreich's ataxia: ligands that mobilize mitochondrial iron. Biochim Biophys Acta 2001; 1536: 133–140.
  • Hentze M, Caughman S, Rouault T et al. Identification of the iron-responsive element for the translational regulation of human ferritin mRNA. Science 1987; 238: 1570–1573.
  • Hentze M, Rouault T, Caughman S, Dancis A, Harford J, Klausner R. A cis-acting element is necessary and sufficient for translational regulation of human ferritin expression in response to iron. Proc Natl Acad Sci USA 1987;84: 6730–6734.
  • May B, Bhasker C, Bawden M, Cox T. Molecular regulation of 5-aminolevulinate synthase. Diseases related to heme biosynthesis. Mol Biol Med 1990;7: 405–421.
  • Cox T, Bawden M, Martin A, May B. Human erythroid 5-aminolevulinate synthase: promoter analysis and identification of an iron-responsive element in the mRNA. EMBO J 1991; 10: 1891–1902.
  • Dandekar T, Stripecke R, Gray N et al. Identification of a novel iron-responsive element in murine and human erythroid delta-aminolevulinic acid synthase mRNA. EMBO J 1991; 10: 1903–1909.
  • Casey J, Hentze M, Koeller D et al. Iron-responsive elements: regulatory RNA sequences that control mRNA levels and translation. Science 1988; 240: 924–928.
  • Wardrop S, Richardson D. The effect of intracellular iron concentration and nitrogen monoxide on Nramp2 expression and non-transferrin-bound iron uptake. Eur J Biochem 1999; 263: 41–49.
  • Gunshin H, Allerson C, Polycarpou-Schwarz M et al. Iron-dependent regulation of the divalent metal ion transporter. FEBS Lett 2001; 509: 309–316.
  • Koeller D, Casey J, Hentze M et al. A cytosolic protein binds to structural elements within the iron regulatory region of the transferrin receptor mRNA. Proc Natl Acad Sci USA 1989; 86: 3574–3578.
  • Hentze M, Kuhn L. Molecular control of vertebrate iron metabolism: mRNA-based regulatory circuits operated by iron, nitric oxide, and oxidative stress. Proc Natl Acad Sci USA 1996; 93: 8175–8182.
  • Wardrop S, Watts R, Richardson D. Nitrogen monoxide activates iron regulatory protein 1 RNA-binding activity by two possible mechanisms: effect on the [4Fe-4S] cluster and iron mobilization from cells. Biochemistry 2000; 39: 2748–2758.
  • Cotran RS, Kumar V, Collins T. Robbins Pathologic Basis of Disease, 6th edn. Philadelphia, PA: W.B. Saunders, 1999; 260-327.
  • Feder J, Gnirke A, Thomas W et al. A novel MHC class I-like gene is mutated in patients with hereditary haemochromatosis. Nat Genet 1996; 13: 399–408.
  • Lyon E, Frank E. Hereditary hemochromatosis since discovery of the HFE gene. Clin Chem 2001;47: 1147–1156.
  • Njajou 0, Vaessen N, Joosse M et al. A mutation in SLC11A3 is associated with autosomal dominant hemochromatosis. Nat Genet 2001;28: 213–214.
  • Montosi G, Donovan A, Totaro A et al. Autosomal-dominant hemochromatosis is associated with a mutation in the ferroportin (SLC11A3) gene. J Clin Invest 2001; 108: 619–623.
  • Lebron J, Bennett M, Vaughn D et al. Crystal structure of the hemochromatosis protein HFE and characterization of its interaction with transferrin receptor. Cell 1998; 93: 111–123.
  • Parkkila S, Waheed A, Britton R et al. Association of the transferrin receptor in human placenta with HFE, the protein defective in hereditary hemochromatosis. Proc Natl Acad Sci USA 1997; 94: 13198–13202.
  • Bennett M, Lebron J, Bjorkman P. Crystal structure of the hereditary haemochromatosis protein HFE complexed with transferrin receptor. Nature 2000; 403: 46–53.
  • Waheed A, Parkkila S, Saarnio J et al. Association of HFE protein with transferrin receptor in crypt enterocytes of human duodenum. Proc Natl Acad Sci USA 1999; 96: 1579–1584.
  • Zoller H, Pietrangelo A, Vogel W, Weiss G. Duodenal metal-transporter (DMT-1, NRAMP-2) expression in patients with hereditary haemochromatosis. Lancet 1999; 353: 2120–2123.
  • Zoller H, Koch R, Theurl I et al. Expression of the duodenal iron transporters divalent-metal transporter 1 and ferroportin 1 in iron deficiency and iron overload. Gastroenterology 2001; 120: 1412–1419.
  • Milman N, Pedersen P, Steig T,Byg K, 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 2001; 80: 737–744.
  • Niederau C, Fischer R, Sonnenberg A, Stremmel W, Trampisch HJ, Strohmyer G. Survival and causes of death in cirrhotic and in noncirrhotic patients with primary hemochromatosis. N Engl J Med 1985; 313: 1256–1262.
  • Bradbear RA, Bain C, Siskind V et al. Cohort study of internal malignancy in genetic hemochromatosis and other chronic non-alcoholic liver diseases. J Natl Cancer Inst 1985; 75: 81–84.
  • Hsing AW, McLaughlin JK, Olsen JH, Mellemkjar L, Wacholder S, Fraumeni JFJ. Cancer risk following primary hemochromatosis: a population-based cohort study in Denmark. Int J Cancer 1995;60: 160–162.
  • Ammann RW, Muller E, Bansky J, Schuler G, Hacki WH. High incidence of extrahepatic carcinomas in idiopathic hemochromatosis. Scand J Gastroenterol 1980; 15: 733–736.
  • Tiniakos G, Williams R. Cirrhotic process, liver cell carcinoma and extrahepatic malignant tumors in idiopathic hemochromatosis. Appl Pathol 1988; 6: 128–138.
  • Mallory M, Kowdley K. Hereditary hemochromatosis and cancer risk: more fuel to the fire? Gastroenterology 2001; 121: 1253–1254.
  • Fellows IW, Stewart M, Jeffcoate WJ, Smith PG. Hepatocellular carcinoma in primary hemochromatosis in the absence of cirrhosis. Gut 1988;29: 1603–1609.
  • Kew MD. Pathogenesis of hepatocellular carcinoma in hereditary hemochromatosis: occurrence in noncirrhotic patients. Hepatology 1990; 6: 1086–1087.
  • Blumberg RS, Chopra S, Ibrahim R et al. Primary hepatocellular carcinoma in idiopathic hemochromatosis after reversal of cirrhosis. Gastroenterology 1988; 95: 1399–1402.
  • Niemela O, Parkkila S, Britton R, Brunt E, Janney C, Bacon B. Hepatic lipid peroxidation in hereditary hemochromatosis and alcoholic liver injury. J Lab Clin Med 1999; 133: 451–460.
  • Grootveld M, Bell JD, Halliwell B, Aruoma 01, Bomford A, Sadler PJ. Non-transferrin-bound iron in plasma or serum from patients with idiopathic hemochromatosis: characterization by high performance liquid chromatography and nuclear magnetic resonance spectroscopy. J Biol Chem 1989; 264:4417–4422.
  • Toyokuni S, Sagripanti JL. Induction of oxidative single- and double-strand breaks in DNA by ferric citrate. Free Radic Biol Med 1993; 15: 117–123.
  • Okada S. Iron-induced tissue damage and cancer: the role of reactive oxygen free radicals. Pathol Int 1996;46: 311–332.
  • Vogelstein B, Kinzler KW. The Genetic Basis of Human Cancer. New York: McGraw-Hill, 1998.
  • Bernstein C. Sex as a response to oxidative DNA damage. In: Halliwell B, Aruoma OI. (eds) DNA and Free Radicals, 1st edn. Chichester: Ellis Horwood, 1993; 193-210.
  • Halliwell B, Gutteridge JMC. Free Radicals in Biology and Medicine, 3rd edn. Oxford: Clarendon, 1999.
  • Toyokuni S. Reactive oxygen species-induced molecular damage and its application in pathology. Pathol Int 1999; 49: 91–102.
  • Tanaka T, Iwasa Y, Kondo S, Hiai H, Toyokuni S. High incidence of allelic loss on chromosome 5 and inactivation of p15Thil' and p16'4A tumor suppressor genes in oxy stress-induced renal cell carcinoma of rats. Oncogene 1999; 18: 3793–3797.
  • Knudson Jr AG, Hethcote HW, Brown BW. Mutation and childhood cancer: a probabilistic model for the incidence of retinoblastoma. Proc Natl Acad Sci USA 1975; 72: 5116–5120.
  • Herman JG, Graff JR, MyohanenS, Nelkin BD, Baylin SB. Methylation-specific PCR: a novel PCR assay for methylation status of CpG islands. Proc Natl Acad Sci USA 1996; 93: 9821–9826.
  • Kamijo T, Weber JD, Zambetti G, Zindy F, Roussel MF, Sherr CJ. Functional and physical interactions of the ARF tumor suppressor with p53 and Mdm2. Proc Natl Acad Sci USA 1998; 95: 8292–8297.
  • Tao W, Levine AJ. P19(ARF) stabilizes p53 by blocking nucleo-cytoplasmic shuttling of Mdm2. Proc Natl Acad Sci USA 1999; 96: 6937–6941.
  • Chan FK, Zhang J, Cheng L, Shapiro DN, Winoto A. Identification of human and mousep/9, a novel CDK4 and CDK6 inhibitor with homology to p16. Mol Cell Biol 1995; 15: 2682–2688.
  • Hiroyasu M, Ozeki M, Kohda H et al. Specific allelic loss of p 16IN“A tumor suppressor gene after weeks of iron-mediated oxidative damage during rat renal carcinogenesis. Am J Pathol 2002; 160:419–424.
  • Sanchez-Cespedes M, Decker P, Doffek K et al. Increased loss of chromosome 9p21 but not pI6 inactivation in primary non-small cell lung cancer from smokers. Cancer Res 2001; 61: 2092–2096.
  • Zhang S, Klein-Szanto A, Sauter E et al. Higher frequency of alterations in the p/6/CDKN2 gene in squamous cell carcinoma cell lines than in primary tumors of the head and neck. Cancer Res 1994; 54: 5050–5053.
  • Vautier G, Bomford A, Portmann B, Metivier E, Williams R, Ryder S. p.53 mutations in British patients with hepatocellular carcinoma: clustering in genetic hemochromatosis. Gastroenterology 1999; 117: 154–160.
  • Marrogi AJ, Khan MA, van Gijssel GH et al. Oxidative stress and p.53 mutations in the carcinogenesis of iron overload-associated hepatocellular carcinoma. J Natl Cancer Inst 2001; 93: 1652–1655.
  • Nair J, Carmichael P, Fernando R, Phillips D, Strain A, Bartsch H. Lipid peroxidation-induced etheno-DNA adducts in the liver of patients with the genetic metal storage disorders Wilson's disease and primary hemochromatosis. Cancer Epidemiol Biomarkers Prey 1998;7: 435–440.

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