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Carcinogenic metals and NF‐κB activation

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Abstract

Epidemiological and animal studies suggest that several metals and metal-containing compounds are potent mutagens and carcinogens. These metals include chromium, arsenic, vanadium, and nickel. During the last two decades, chemical and cellular studies have contributed enormously to our understanding of the mechanisms of metal-induced pathophysiological processes. Although each of these metals is unique in its mechanism of action, some common signaling molecules, such as reactive oxygen species (ROS), may be shared by many of these carcinogenic metals. New techniques are now available to reveal the mechanisms of carcinogenesis in precise molecular terms. In this review, we focused our attentions on metal-induced signal transduction pathways leading to the activation of NF-κB, a transcription factor governing the expression of most early response genes involved in a number of human diseases.

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References

  1. Sarkar B: Metal replacement in DNA-binding zinc finger proteins and its relevance to mutagenicity and carcinogenicity through free radical generation. Nutrition 11: 646–649, 1995

    Google Scholar 

  2. Pollan M, Gustavsson P: High-risk occupations for breast cancer in the Swedish female working population. Am J Public Health 89: 875–881, 1999

    Google Scholar 

  3. Maier H, Tisch M: Epidemiology of laryngeal cancer: Results of the Heidelberg case-control study. Acta Otolaryngol Suppl 527: 160–164, 1997

    Google Scholar 

  4. Snow ET: Metal carcinogenesis: Mechanistic implications. Pharmacol Ther 53: 31–65, 1992

    Google Scholar 

  5. Hanahan D, Weinberg RA: The hallmarks of cancer. Cell 100: 57–70, 2000

    Google Scholar 

  6. Hamilton JW, Kaltreider RC, Bajenova OV, Ihnat MA, McCaffrey J, Turpie BW, Rowell EE, Oh J, Nemeth MJ, Pesce CA, Lariviere JP: Molecular basis for effects of carcinogenic heavy metals on inducible gene expression. Environ Health Perspect 106 (suppl 4): 1005–1015, 1998

    Google Scholar 

  7. Bartsch H, Nair J: New DNA-based biomarkers for oxidative stress and cancer chemoprevention studies. Eur J Cancer 36: 1229–1234, 2000

    Google Scholar 

  8. Karin M, Ben-Neriah Y: Phosphorylation meets ubiquitination: The control of NF-[kappa]B activity. Annu Rev Immunol 18: 621–663, 2000

    Google Scholar 

  9. Chen F, Castranova V, Shi X, Demers LM: New insights into the role of nuclear factor-kappaB, a ubiquitous transcription factor in the initiation of diseases. Clin Chem 45: 7–17, 1999

    Google Scholar 

  10. Pahl HL: Activators and target genes of Rel/NF-kappaB transcription factors. Oncogene 18: 6853–6866, 1999

    Google Scholar 

  11. Gilmore TD: The Rel/NF-kappaB signal transduction pathway: Introduction. Oncogene 18: 6842–6844, 1999

    Google Scholar 

  12. Sun SC, Ballard DW: Persistent activation of NF-kappaB by the tax transforming protein of HTLV-1: Hijacking cellular IkappaB kinases. Oncogene 18: 6948–6958, 1999

    Google Scholar 

  13. Neish AS, Gewirtz AT, Zeng H, Young AN, Hobert ME, Karmali V, Rao AS, Madara JL: Prokaryotic regulation of epithelial responses by inhibition of IkappaB-alpha ubiquitination. Science 289: 1560–1563, 2000

    Google Scholar 

  14. Palombella VJ, Rando OJ, Goldberg AL, Maniatis T: The ubiquitinproteasome pathway is required for processing the NF-kappa B1 precursor protein and the activation of NF-kappa B. Cell 78: 773–785, 1994

    Google Scholar 

  15. Woronicz JD, Gao X, Cao Z, Rothe M, Goeddel DV: IkappaB kinase-beta: NF-kappaB activation and complex formation with IkappaB kinase-alpha and NIK. Science 278: 866–869, 1997

    Google Scholar 

  16. Mercurio F, Zhu H, Murray BW, Shevchenko A, Bennett BL, Li J, Young DB, Barbosa M, Mann M, Manning A, Rao A: IKK-1 and IKK-2: Cytokine-activated IkappaB kinases essential for NF-kappaB activation. Science 278: 860–866, 1997

    Google Scholar 

  17. Cohen L, Henzel WJ, Baeuerle PA: IKAP is a scaffold protein of the IkappaB kinase complex. Nature 395: 292–296, 1998

    Google Scholar 

  18. Krappmann D, Hatada EN, Tegethoff S, Li J, Klippel A, Giese K, Baeuerle PA, Scheidereit C: The ikappa B kinase (IKK) complex is tripartite and contains IKKgamma but not IKAP as a regular component. J Biol Chem 275: 29779–29787, 2000

    Google Scholar 

  19. Li X, Commane M, Nie H, Hua X, Chatterjee-Kishore M, Wald D, Haag M, Stark GR: Act1, an NF-kappa B-activating protein. Proc Natl Acad Sci USA 97: 10489–10493, 2000

    Google Scholar 

  20. Leonardi A, Chariot A, Claudio E, Cunningham K, Siebenlist U: CIKS, a connection to Ikappa B kinase and stress-activated protein kinase. Proc Natl Acad Sci USA 97: 10494–10499, 2000

    Google Scholar 

  21. Israel A: The IKK complex: An integrator of all signals that activate NF-kappaB? Trends Cell Biol 10: 129–133, 2000

    Google Scholar 

  22. Tojima Y, Fujimoto A, Delhase M, Chen Y, Hatakeyama S, Nakayama K, Kaneko Y, Nimura Y, Motoyama N, Ikeda K, Karin M, Nakanishi M: NAK is an IkappaB kinase-activating kinase. Nature 404: 778–782, 2000

    Google Scholar 

  23. Li N, Karin M: Ionizing radiation and short wavelength UV activate NF-kappaB through two distinct mechanisms. Proc Natl Acad Sci USA 95: 13012–13017, 1998

    Google Scholar 

  24. Bender K, Gottlicher M, Whiteside S, Rahmsdorf HJ, Herrlich P: Sequential DNA damage-independent and-dependent activation of NF-kappaB by UV. Embo J 17: 5170–5181, 1998

    Google Scholar 

  25. Lee FS, Hagler J, Chen ZJ, Maniatis T: Activation of the IkappaB 169 alpha kinase complex by MEKK1, a kinase of the JNK pathway. Cell 88: 213–222, 1997

    Google Scholar 

  26. Pomerantz JL, Baltimore D: NF-kappaB activation by a signaling complex containing TRAF2, TANK and TBK1, a novel IKK-related kinase. Embo J 18: 6694–6704, 1999

    Google Scholar 

  27. Ozes ON, Mayo LD, Gustin JA, Pfeffer SR, Pfeffer LM, Donner DB: NF-kappaB activation by tumour necrosis factor requires the Akt serine-threonine kinase. Nature 401: 82–85, 1999

    Google Scholar 

  28. Romashkova JA, Makarov SS: NF-kappaB is a target of AKT in anti-apoptotic PDGF signalling. Nature 401: 86–90, 1999

    Google Scholar 

  29. Sun Z, Arendt CW, Ellmeier W, Schaeffer EM, Sunshine MJ, Gandhi L, Annes J, Petrzilka D, Kupfer A, Schwartzberg PL, Littman DR: PKC-theta is required for TCR-induced NF-kappaB activation in mature but not immature T lymphocytes. Nature 404: 402–407, 2000

    Google Scholar 

  30. Lin X, O'Mahony A, Mu Y, Geleziunas R, Greene WC: Protein kinase C-theta participates in NF-kappaB activation induced by CD3-CD28 costimulation through selective activation of IkappaB kinase beta. Mol Cell Biol 20: 2933–2940, 2000

    Google Scholar 

  31. Lallena MJ, Diaz-Meco MT, Bren G, Paya CV, Moscat J: Activation of IkappaB kinase beta by protein kinase C isoforms. Mol Cell Biol 19: 2180–2188, 1999

    Google Scholar 

  32. Lin X, Cunningham ET, Jr., Mu Y, Geleziunas R, Greene WC: The proto-oncogene Cot kinase participates in CD3/CD28 induction of NF-kappaB acting through the NF-kappaB-inducing kinase and IkappaB kinases. Immunity 10: 271–280, 1999

    Google Scholar 

  33. Zamanian-Daryoush M, Mogensen TH, DiDonato JA, Williams BR: NF-kappaB activation by double-stranded-RNA-activated protein kinase (PKR) is mediated through NF-kappaB-inducing kinase and IkappaB kinase. Mol Cell Biol 20: 1278–1290, 2000

    Google Scholar 

  34. Hehner SP, Hofmann TG, Ushmorov A, Dienz O, Wing-Lan Leung I, Lassam N, Scheidereit C, Droge W, Schmitz ML: Mixed-lineage kinase 3 delivers CD3/CD28-derived signals into the IkappaB kinase complex. Mol Cell Biol 20: 2556–2568, 2000

    Google Scholar 

  35. Minden A, Lin A, McMahon M, Lange-Carter C, Derijard B, Davis RJ, Johnson GL, Karin M: Differential activation of ERK and JNK mitogen-activated protein kinases by Raf-1 and MEKK. Science 266: 1719–1723, 1994

    Google Scholar 

  36. Yan M, Dai T, Deak JC, Kyriakis JM, Zon LI, Woodgett JR, Templeton DJ: Activation of stress-activated protein kinase by MEKK1 phosphorylation of its activator SEK1. Nature 372: 798–800, 1994

    Google Scholar 

  37. Lee FS, Peters RT, Dang LC, Maniatis T: MEKK1 activates both IkappaB kinase alpha and IkappaB kinase beta. Proc Natl Acad Sci USA 95: 9319–9324, 1998

    Google Scholar 

  38. Meyer CF, Wang X, Chang C, Templeton D, Tan TH: Interaction between c-Rel and the mitogen-activated protein kinase kinase kinase 1 signaling cascade in mediating kappaB enhancer activation. J Biol Chem 271: 8971–8976, 1996

    Google Scholar 

  39. Hirano M, Osada S, Aoki T, Hirai S, Hosaka M, Inoue J, Ohno S: MEK kinase is involved in tumor necrosis factor alpha-induced NF-kappaB activation and degradation of IkappaB-alpha. J Biol Chem 271: 13234–13238, 1996

    Google Scholar 

  40. Yin MJ, Christerson LB, Yamamoto Y, Kwak YT, Xu S, Mercurio F, Barbosa M, Cobb MH, Gaynor RB: HTLV-I Tax protein binds to MEKK1 to stimulate IkappaB kinase activity and NF-kappaB activation. Cell 93: 875–884, 1998

    Google Scholar 

  41. Kopp E, Medzhitov R, Carothers J, Xiao C, Douglas I, Janeway CA, Ghosh S: ECSIT is an evolutionarily conserved intermediate in the Toll/IL-1 signal transduction pathway. Genes Dev 13: 2059–2071, 1999

    Google Scholar 

  42. Xia Y, Makris C, Su B, Li E, Yang J, Nemerow GR, Karin M: MEK kinase 1 is critically required for c-Jun N-terminal kinase activation by proinflammatory stimuli and growth factor-induced cell migration. Proc Natl Acad Sci USA 97: 5243–5248, 2000

    Google Scholar 

  43. DiDonato JA, Hayakawa M, Rothwarf DM, Zandi E, Karin M: A cytokine-responsive IkappaB kinase that activates the transcription factor NF-kappaB. Nature 388: 548–554, 1997

    Google Scholar 

  44. Malinin NL, Boldin MP, Kovalenko AV, Wallach D: MAP3K-related kinase involved in NF-kappaB induction by TNF, CD95 and IL-1. Nature 385: 540–544, 1997

    Google Scholar 

  45. Song HY, Regnier CH, Kirschning CJ, Goeddel DV, Rothe M: Tumor necrosis factor (TNF)-mediated kinase cascades: Bifurcation of nuclear factor-kappaB and c-jun N-terminal kinase (JNK/ SAPK) pathways at TNF receptor-associated factor 2. Proc Natl Acad Sci USA 94: 9792–9796, 1997

    Google Scholar 

  46. Regnier CH, Song HY, Gao X, Goeddel DV, Cao Z, Rothe M: Identification and characterization of an IkappaB kinase. Cell 90: 373–383, 1997

    Google Scholar 

  47. Nakano H, Shindo M, Sakon S, Nishinaka S, Mihara M, Yagita H, Okumura K: Differential regulation of IkappaB kinase alpha and beta by two upstream kinases, NF-kappaB-inducing kinase and mitogen-activated protein kinase/ERK kinase kinase-1. Proc Natl Acad Sci USA 95: 3537–3542, 1998

    Google Scholar 

  48. Natoli G, Costanzo A, Moretti F, Fulco M, Balsano C, Levrero M: Tumor necrosis factor (TNF) receptor 1 signaling downstream of TNF receptor-associated factor 2. Nuclear factor kappaB (NFkappaB)-inducing kinase requirement for activation of activating protein 1 and NFkappaB but not of c-Jun N-terminal kinase/stress-activated protein kinase. J Biol Chem 272: 26079–26082, 1997

    Google Scholar 

  49. Kirschning CJ, Wesche H, Merrill Ayres T, Rothe M: Human toll-like receptor 2 confers responsiveness to bacterial lipopolysaccharide. J Exp Med 188: 2091–2097, 1998

    Google Scholar 

  50. Muzio M, Natoli G, Saccani S, Levrero M, Mantovani A: The human toll signaling pathway: Divergence of nuclear factor kappaB and JNK/SAPK activation upstream of tumor necrosis factor receptor-associated factor 6 (TRAF6). J Exp Med 187: 2097–2101, 1998

    Google Scholar 

  51. Sylla BS, Hung SC, Davidson DM, Hatzivassiliou E, Malinin NL, Wallach D, Gilmore TD, Kieff E, Mosialos G: Epstein-Barr virus-transforming protein latent infection membrane protein 1 activates transcription factor NF-kappaB through a pathway that includes the NF-kappaB-inducing kinase and the IkappaB kinases IKKalpha and IKKbeta. Proc Natl Acad Sci USA 95: 10106–10111, 1998

    Google Scholar 

  52. Shinkura R, Kitada K, Matsuda F, Tashiro K, Ikuta K, Suzuki M, Kogishi K, Serikawa T, Honjo T: Alymphoplasia is caused by a point mutation in the mouse gene encoding Nf-kappa b-inducing kinase. Nat Genet 22: 74–77, 1999

    Google Scholar 

  53. Peters RT, Liao SM, Maniatis T: IKKepsilon is part of a novel PMA-inducible IkappaB kinase complex. Mol Cell 5: 513–522, 2000

    Google Scholar 

  54. Khwaja A: Akt is more than just a Bad kinase. Nature 401: 33–34, 1999

    Google Scholar 

  55. Xie P, Browning DD, Hay N, Mackman N, Ye RD: Activation of NF-kappa B by bradykinin through a Galpha (q)-and Gbeta gamma-dependent pathway that involves phosphoinositide 3-kinase and Akt. J Biol Chem 275: 24907–24914, 2000

    Google Scholar 

  56. Delhase M, Li N, Karin M: Kinase regulation in inflammatory response. Nature 406: 367–368, 2000

    Google Scholar 

  57. Madge LA, Pober JS: A phosphatidylinositol 3-kinase/Akt pathway, activated by tumor necrosis factor or interleukin-1, inhibits apoptosis but does not activate NFkappaB in human endothelial cells. J Biol Chem 275: 15458–15465, 2000

    Google Scholar 

  58. Rauch BH, Weber A, Braun M, Zimmermann N, Schror K: PDGF-induced Akt phosphorylation does not activate NF-kappa B in 170 human vascular smooth muscle cells and fibroblasts. FEBS Lett 481: 3–7, 2000

    Google Scholar 

  59. Sizemore N, Leung S, Stark GR: Activation of phosphatidylinositol 3-kinase in response to interleukin-1 leads to phosphorylation and activation of the NF-kappaB p65/RelA subunit. Mol Cell Biol 19: 4798–4805, 1999

    Google Scholar 

  60. Madrid LV, Wang CY, Guttridge DC, Schottelius AJ, Baldwin AS Jr, Mayo MW: Akt suppresses apoptosis by stimulating the transactivation potential of the RelA/p65 subunit of NF-kappaB. Mol Cell Biol 20: 1626–1638, 2000

    Google Scholar 

  61. Kane LP, Shapiro VS, Stokoe D, Weiss A: Induction of NF-kappaB by the Akt/PKB kinase. Curr Biol 9: 601–604, 1999

    Google Scholar 

  62. Pullen N, Dennis PB, Andjelkovic M, Dufner A, Kozma SC, Hemmings BA, Thomas G: Phosphorylation and activation of p70s6k by PDK1. Science 279: 707–710, 1998

    Google Scholar 

  63. Peterson RT, Schreiber SL: Kinase phosphorylation: Keeping it all in the family. Curr Biol 9: R521–524, 1999

    Google Scholar 

  64. Teramoto H, Coso OA, Miyata H, Igishi T, Miki T, Gutkind JS: Signaling from the small GTP-binding proteins Rac1 and Cdc42 to the c-Jun N-terminal kinase/stress-activated protein kinase pathway. A role for mixed lineage kinase 3/protein-tyrosine kinase 1, a novel member of the mixed lineage kinase family. J Biol Chem 271: 27225–27228, 1996

    Google Scholar 

  65. Sakurai H, Miyoshi H, Toriumi W, Sugita T: Functional interactions of transforming growth factor beta-activated kinase 1 with IkappaB kinases to stimulate NF-kappaB activation. J Biol Chem 274: 10641–10648, 1999

    Google Scholar 

  66. Ninomiya-Tsuji J, Kishimoto K, Hiyama A, Inoue J, Cao Z, Matsumoto K: The kinase TAK1 can activate the NIK-I kappaB as well as the MAP kinase cascade in the IL-1 signalling pathway. Nature 398: 252–256, 1999

    Google Scholar 

  67. Chen F, Ding M, Lu Y, Leonard SS, Vallyathan V, Castranova V, Shi X: Participation of MAP kinase p38 and IkappaB kinase in chromium (VI)-induced NF-kappaB and AP-1 activation. J Environ Pathol Toxicol Oncol 19: 231–238, 2000

    Google Scholar 

  68. Huang C, Chen N, Ma WY, Dong Z: Vanadium induces AP-1-and NFkappB-dependent transcription activity. Int J Oncol 13: 711–715, 1998

    Google Scholar 

  69. Kaltreider RC, Pesce CA, Ihnat MA, Lariviere JP, Hamilton JW: Differential effects of arsenic (III) and chromium (VI) on nuclear transcription factor binding. Mol Carcinog 25: 219–229, 1999

    Google Scholar 

  70. Roussel RR, Barchowsky A: Arsenic inhibits NF-kappaB-mediated gene transcription by blocking IkappaB kinase activity and IkappaBalpha phosphorylation and degradation. Arch Biochem Biophys 377: 204–212, 2000

    Google Scholar 

  71. Shumilla JA, Broderick RJ, Wang Y, Barchowsky A: Chromium (VI) inhibits the transcriptional activity of nuclear factor-kappaB by decreasing the interaction of p65 with cAMP-responsive element-binding protein-binding protein. J Biol Chem 274: 36207–36212, 1999

    Google Scholar 

  72. Barchowsky A, Dudek EJ, Treadwell MD, Wetterhahn KE: Arsenic induces oxidant stress and NF-kappa B activation in cultured aortic endothelial cells. Free Radic Biol Med 21: 783–790, 1996

    Google Scholar 

  73. Jaspers I, Samet JM, Reed W: Arsenite exposure of cultured airway epithelial cells activates kappaB-dependent interleukin-8 gene expression in the absence of nuclear factor-kappaB nuclear translocation. J Biol Chem 274: 31025–31033, 1999

    Google Scholar 

  74. Shumilla JA, Wetterhahn KE, Barchowsky A: Inhibition of NF-kappa B binding to DNA by chromium, cadmium, mercury, zinc, and arsenite in vitro: Evidence of a thiol mechanism. Arch Biochem Biophys 349: 356–362, 1998

    Google Scholar 

  75. Kapahi P, Takahashi T, Natoli G, Adams SR, Chen Y, Tsien RY, Karin M: Inhibition of NF-kappa B activation by arsenite through reaction with a critical cysteine in the activation loop of Ikappa B kinase. J Biol Chem 275: 36062–36066, 2000

    Google Scholar 

  76. Schieven GL, Kirihara JM, Myers DE, Ledbetter JA, Uckun FM: Reactive oxygen intermediates activate NF-kappa B in a tyrosine kinase-dependent mechanism and in combination with vanadate activate the p56lck and p59fyn tyrosine kinases in human lymphocytes. Blood 82: 1212–1220, 1993

    Google Scholar 

  77. Imbert V, Rupec RA, Livolsi A, Pahl HL, Traenckner EB, Mueller-Dieckmann C, Farahifar D, Rossi B, Auberger P, Baeuerle PA, Peyron JF: Tyrosine phosphorylation of I kappa B-alpha activates NF-kappa B without proteolytic degradation of I kappa B-alpha. Cell 86: 787–798, 1996

    Google Scholar 

  78. Klebanoff SJ, Watts DH, Mehlin C, Headley CM: Lactobacilli and vaginal host defense: Activation of the human immunodeficiency virus type 1 long terminal repeat, cytokine production, and NF-kappaB. J Infect Dis 179: 653–660, 1999

    Google Scholar 

  79. Chen F, Demers LM, Vallyathan V, Ding M, Lu Y, Castranova V, Shi X: Vanadate induction of NF-kappaB involves IkappaB kinase beta and SAPK/ERK kinase 1 in macrophages. J Biol Chem 274: 20307–20312, 1999

    Google Scholar 

  80. Singh S, Aggarwal BB: Protein-tyrosine phosphatase inhibitors block tumor necrosis factor-dependent activation of the nuclear transcription factor NF-kappa B. J Biol Chem 270: 10631–10639, 1995

    Google Scholar 

  81. Mukhopadhyay A, Manna SK, Aggarwal BB: Pervanadate-induced nuclear factor-kappaB activation requires tyrosine phosphorylation and degradation of IkappaBalpha. Comparison with tumor necrosis factor-alpha. J Biol Chem 275: 8549–8555, 2000

    Google Scholar 

  82. Krejsa CM, Nadler SG, Esselstyn JM, Kavanagh TJ, Ledbetter JA, Schieven GL: Role of oxidative stress in the action of vanadium phosphotyrosine phosphatase inhibitors. Redox independent activation of NF-kappaB. J Biol Chem 272: 11541–11549, 1997

    Google Scholar 

  83. Barbeau B, Bernier R, Dumais N, Briand G, Olivier M, Faure R, Posner BI, Tremblay M: Activation of HIV-1 long terminal repeat transcription and virus replication via NF-kappaB-dependent and-independent pathways by potent phosphotyrosine phosphatase inhibitors, the peroxovanadium compounds. J Biol Chem 272: 12968–12977, 1997

    Google Scholar 

  84. Jaspers I, Samet JM, Erzurum S, Reed W: Vanadium-induced kappaB-dependent transcription depends upon peroxide-induced activation of the p38 mitogen-activated protein kinase. Am J Respir Cell Mol Biol 23: 95–102, 2000

    Google Scholar 

  85. Beraud C, Henzel WJ, Baeuerle PA: Involvement of regulatory and catalytic subunits of phosphoinositide 3-kinase in NF-kappaB activation. Proc Natl Acad Sci USA 96: 429–434, 1999

    Google Scholar 

  86. Barceloux DG: Chromium. J Toxicol Clin Toxicol 37: 173–194, 1999

    Google Scholar 

  87. Alexander BH, Checkoway H, Wechsler L, Heyer NJ, Muhm JM, O'Keeffe TP: Lung cancer in chromate-exposed aerospace workers. J Occup Environ Med 38: 1253–1258, 1996

    Google Scholar 

  88. Ye J, Zhang X, Young HA, Mao Y, Shi X: Chromium (VI)-induced nuclear factor-kappa B activation in intact cells via free radical reactions. Carcinogenesis 16: 2401–2405, 1995

    Google Scholar 

  89. Shi X, Chiu A, Chen CT, Halliwell B, Castranova V, Vallyathan V: Reduction of chromium (VI) and its relationship to carcinogenesis. J Toxicol Environ Health B Crit Rev 2: 87–104, 1999

    Google Scholar 

  90. Shi XL, Dalal NS: Chromium (V) and hydroxyl radical formation during the gl tathione reductase-catalyzed reduction of chromium (VI). Biochem Biophys Res Commun 163: 627–634, 1989

    Google Scholar 

  91. Shi XL, Dalal NS: NADPH-dependent flavoenzymes catalyze one electron reduction of metal ions and molecular oxygen and generate hydroxyl radicals. FEBS Lett 276: 189–191, 1990

    Google Scholar 

  92. Shi XL, Dalal NS: The role of superoxide radical in chromium (VI)-generated hydroxyl radical: The Cr (VI) Haber-Weiss cycle. Arch Biochem Biophys 292: 323–327, 1992

    Google Scholar 

  93. Janssen-Heininger YM, Poynter ME, Baeuerle PA: Recent advances towards understanding redox mechanisms in the activation of nuclear factor kappaB. Free Radic Biol Med 28: 1317–1327, 2000

    Google Scholar 

  94. Flohe L, Brigelius-Flohe R, Saliou C, Traber MG, Packer L: Redox regulation of NF-kappa B activation. Free Radic Biol Med 22: 1115–1126, 1997

    Google Scholar 

  95. Ginn-Pease ME, Whisler RL: Redox signals and NF-kappaB activation in T cells. Free Radic Biol Med 25: 346–361, 1998

    Google Scholar 

  96. Bonizzi G, Piette J, Merville MP, Bours V: Cell type-specific role for reactive oxygen species in nuclear factor-kappaB activation by interleukin-1. Biochem Pharmacol 59: 7–11, 2000

    Google Scholar 

  97. Bowie A, O'Neill LA: Oxidative stress and nuclear factor-kappaB activation: A reassessment of the evidence in the light of recent discoveries. Biochem Pharmacol 59: 13–23, 2000

    Google Scholar 

  98. Dalton TP, Shertzer HG, Puga A: Regulation of gene expression by reactive oxygen. Annu Rev Pharmacol Toxicol 39: 67–101, 1999

    Google Scholar 

  99. Davies KJ: Oxidative stress: The paradox of aerobic life. Biochem Soc Symp 61: 1–31, 1995

    Google Scholar 

  100. Buzard GS, Kasprzak KS: Possible roles of nitric oxide and redox cell signaling in metal-induced toxicity and carcinogenesis: A review. J Environ Pathol Toxicol Oncol 19: 179–199, 2000

    Google Scholar 

  101. Schreck R, Meier B, Mannel DN, Droge W, Baeuerle PA: Dithiocarbamates as potent inhibitors of nuclear factor kappa B activation in intact cells. J Exp Med 175: 1181–1194, 1992

    Google Scholar 

  102. Li N, Karin M: Is NF-kappaB the sensor of oxidative stress? Faseb J 13: 1137–1143, 1999

    Google Scholar 

  103. Roederer M, Staal FJ, Raju PA, Ela SW, Herzenberg LA: Cytokine-stimulated human immunodeficiency virus replication is inhibited by N-acetyl-L-cysteine. Proc Natl Acad Sci USA 87: 4884–4888, 1990

    Google Scholar 

  104. Matthews JR, Wakasugi N, Virelizier JL, Yodoi J, Hay RT: Thioredoxin regulates the DNA binding activity of NF-kappa B by reduction of a disulphide bond involving cysteine 62. Nucleic Acids Res 20: 3821–3830, 1992

    Google Scholar 

  105. Matthews JR, Watson E, Buckley S, Hay RT: Interaction of the C-terminal region of p105 with the nuclear localisation signal of p50 is required for inhibition of NF-kappa B DNA binding activity. Nucleic Acids Res 21: 4516–4523, 1993

    Google Scholar 

  106. Matthews JR, Kaszubska W, Turcatti G, Wells TN, Hay RT: Role of cysteine62 in DNA recognition by the P50 subunit of NF-kappa B. Nucleic Acids Res 21: 1727–1734, 1993

    Google Scholar 

  107. Cavigelli M, Li WW, Lin A, Su B, Yoshioka K, Karin M: The tumor promoter arsenite stimulates AP-1 activity by inhibiting a JNK phosphatase. Embo J 15: 6269–6279, 1996

    Google Scholar 

  108. Pugazhenthi S, Tanha F, Dahl B, Khandelwal RL: Inhibition of a Src homology 2 domain containing protein tyrosine phosphatase by vanadate in the primary culture of hepatocytes. Arch Biochem Biophys 335: 273–282, 1996

    Google Scholar 

  109. Denu JM, Dixon JE: Protein tyrosine phosphatases: Mechanisms of catalysis and regulation. Curr Opin Chem Biol 2: 633–641, 1998

    Google Scholar 

  110. Fetrow JS, Siew N, Skolnick J: Structure-based functional motif identifies a potential disulfide oxidoreductase active site in the serine/threonine protein phosphatase-1 subfamily. FASEB J 13: 1866–1874, 1999

    Google Scholar 

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Chen, F., Ding, M., Castranova, V. et al. Carcinogenic metals and NF‐κB activation. Mol Cell Biochem 222, 159–171 (2001). https://doi.org/10.1023/A:1017962113235

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