International Journal of Radiation Oncology * Biology * Physics
Volume 73, Issue 3 , Pages 886-896 , 1 March 2009

Amifostine Induces Antioxidant Enzymatic Activities in Normal Tissues and a Transplantable Tumor That Can Affect Radiation Response

  • David J. Grdina, Ph.D.

      Affiliations

    • Department of Radiation and Cellular Oncology, The University of Chicago, Chicago, IL
    • Corresponding Author InformationReprint requests to: David J. Grdina, Ph.D., The University of Chicago, Department of Radiation and Cellular Oncology; 5841 S. Maryland Ave., MC1105; Chicago, IL 60637. Tel: (773) 702-5250; Fax: (773) 702-5740
    • ,
  • Jeffrey S. Murley, Ph.D.

      Affiliations

    • Department of Radiation and Cellular Oncology, The University of Chicago, Chicago, IL
    • ,
  • Yasushi Kataoka, Ph.D.

      Affiliations

    • Department of Radiation and Cellular Oncology, The University of Chicago, Chicago, IL
    • ,
  • Kenneth L. Baker, B.S.

      Affiliations

    • Department of Radiation and Cellular Oncology, The University of Chicago, Chicago, IL
    • ,
  • Rangesh Kunnavakkam, M.P.H.

      Affiliations

    • Department of Health Studies, The University of Chicago, Chicago, IL
    • ,
  • Mitchell C. Coleman, B.A.

      Affiliations

    • Free Radical and Radiation Biology Program, Department of Radiation Oncology, Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IA
    • ,
  • Douglas R. Spitz, Ph.D.

      Affiliations

    • Free Radical and Radiation Biology Program, Department of Radiation Oncology, Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IA

Received 21 August 2008 ,Revised 3 October 2008 ,Accepted 8 October 2008.

References 

  1. Kouvaris JR, Kouloulias VE, Vlahos LJ. Amifostine: The first selective-target and broad-spectrum radioprotector. Oncologist. 2007;12:738–747
  2. Smoluk GD, Fahey RC, Calabro-Jones , et al. Radioprotection of cells in culture by WR2721 and derivatives: Form of the drug responsible for protection. Cancer Res. 1988;48:3641–3647
  3. Giambarresi L, Jacobs AJ. Radioprotectants. In:  Conklin JJ,  Walker RI editor. Military radiobiology. Orlando, FL: Academic Press; 1987;p. 265–301
  4. Das KC, Lewis-Molock Y, White CW. Activation of NF-Kb and elevation of MnSOD gene expression by thiol reducing agents in lung adenocarcinoma (A549) cells. Am J Physiol. 1995;269:L588–L602
  5. Antras-Ferry J, Maheo K, Chevanne M, et al. Oltipraz stimulates the transcription of the manganese superoxide dismutase gene in rat hepatocytes. Carcinogenesis. 1997;18:2113–2117
  6. Sun J, Chen Y, Li M, et al. Role of antioxidant enzymes on ionizing radiation resistance. Free Radic Biol Med. 1998;24:586–593
  7. Epperly MW, Gretton JE, Sikora CA, et al. Mitochondrial localization of superoxide dismutase is required for decreasing radiation-induced cellular damage. Radiat Res. 2003;160:568–578
  8. Guo G, Yan-Sanders Y, Lyn-Cook BD, et al. Manganese superoxide dismutase-mediated gene expression in radiation-induced adaptive responses. Mol Cell Biol. 2003;23:2362–2378
  9. Greenberger JS, Epperly MW. Antioxidant gene therapeutic approaches to normal tissue radioprotection and tumor radiosensitization. In Vivo. 2007;21:141–146
  10. Niu Y, Epperly MW, Shen H, et al. Intraesophageal MnSOD-plasmid liposome enhances engraftment and self-renewal of bone marrow derived progenitors of esophageal squamous epithelium. Gene Ther. 2008;15:347–356
  11. Zhang X, Epperly MW, Kay MA, et al. Radioprotection in vitro and in vivo by mini circle plasmid containing the human manganese superoxide dismutase (MnSOD) transgene. Hum Gene Ther. 2008;19:820–826
  12. Matthews JR, Wakasugi N, Virelizier JL, et al. Thioredoxin regulates the DNA binding activity of NFκB by reduction of the disulphide bond involving cysteine 62. Nucleic Acids Res. 1992;20:3821–3830
  13. Murley JS, Kataoka Y, Hallahan DE, et al. Activation of NFκB and MnSOD gene expression by free radical scavengers in human microvascular endothelial cells. Free Radic Biol Med. 2001;30:1426–1439
  14. Xu Y, Kiningham KK, Devalaraja MN, et al. An intronic NFκB element is essential for induction of the human manganese superoxide dismutase gene by tumor necrosis factor-α and interleukin 1β. DNA Cell Biol. 1999;18:709–722
  15. Murley JS, Kataoka Y, Weydert CJ, et al. Delayed cytoprotection after enhancement of Sod2 (MnSOD) gene expression in SA-NH mouse sarcoma cells exposed to WR-1065, the active metabolite of amifostine. Radiat Res. 2002;158:101–109
  16. Murley JS, Kataoka Y, Cao D, et al. Delayed radioprotection by NF-κB-mediated induction of Sod2 (MnSOD) in SA-NH tumor cells after exposure to clinically used thiol-containing drugs. Radiat Res. 2004;162:536–546
  17. Murley JS, Kataoka Y, Weydert CJ, et al. Delayed radioprotection by nuclear transcription factor κB-mediated induction of manganese superoxide dismutase in human microvascular endothelial cells after exposure to the free radical scavenger WR1065. Free Radic Biol Med. 2006;40:1004–1016
  18. Murley JS, Kataoka Y, Baker KL, et al. Manganese superoxide dismutase (SOD2)-mediated delayed radioprotection induced by the free thiol form of amifostine and tumor necrosis factor α. Radiat Res. 2007;167:465–474
  19. Murley JS, Nantajit D, Baker KL, et al. Maintenance of manganese superoxide dismutase (SOD2)-mediated delayed radioprotection induced by repeated administration of the free thiol form of amifostine. Radiat Res. 2008;169:494–505
  20. Volpe JP, Hunter B, Basic I, et al. Metastatic properties of murine sarcomas and carcinomas. I. Positive correlation with lung colonization and lack of correlation with s.c. tumor take. Clin Exp Met. 1985;3:281–294
  21. Grdina DJ, Kataoka Y, Murley JS, et al. Inhibition of spontaneous metastases formation by amifostine. Int J Cancer. 2002;97:135–141
  22. Grdina DJ, Linde S, Mason K. Response of selected tumor cell populations separated from a fibrosarcoma following irradiation in situ with fast neutrons. Br J Radiol. 1978;51:291–301
  23. Spitz DR, Oberley LW. An assay for superoxide dismutase activity in mammalian tissue homogenates. Anal Biochem. 1989;179:8–18
  24. Aebi H. Catalase in vitro. Methods Enzymol. 1984;105:121–126
  25. Lawrence RA, Burk RF. Glutathione peroxidase activity in selenium-deficient rat liver. Biochem Biophys Res Commun. 1976;71:952–958
  26. Stata Statistical Software: Release 10.0. College Station, TX: Stata Corporation; 2007;
  27. In:  Daly LE,  Bourke GJ editor. Comparison of more than two independent groups. Intrepretation and uses of medical statistics. Fifth edition. Oxford, UK: Blackwell Science; 2000;p. 296–338
  28. Grdina DJ, Kataoka Y, Murley JS. Amifostine: Mechanisms of action underlying cytoprotection and chemoprevention. Drug Metabol Drug Interact. 2000;16:237–279
  29. Shaw LM, Bonner HS, Brown DQ. Metabolic pathways of WR-2721 (Ethyol, amifostine) in the BALB/c mouse. Drug Metab Dispos. 1994;22:895–902
  30. Shaw LM, Bonner HS, Schuchter L, et al. Pharmacokinetics of amifostine: Effects of dose and method of administration. Semin Oncol. 1999;26(Suppl 7):34–36
  31. Lindegaard JC, Grau C. Has the outlook improved for amifostine as a clinical radioprotector?. Radiother Oncol. 2000;57:113–118
  32. Brizel DM, Wasserman TH, Henke M, et al. Phase III randomized trial of amifostine as a radioprotector in head and neck cancer. J Clin Oncol. 2000;18:3339–3345
  33. Brizel DM. Pharmacologic approaches to radiation protection. J Clin Oncol. 2007;25:4084–4089
  34. Sasse AD, Oliveira Clark LG, Sasse EC, et al. Amifostine reduces side effects and improves complete response rate during radiotherapy: Results of a meta-analysis. Int J Radiat Oncol Biol Phys. 2006;64:784–791
  35. Mell LK, Malik R, Komaki R, et al. Effect of amifostine on response rates in locally advanced non-small-cell lung cancer patients treated on randomized controlled trials: A meta-analysis. Int J Radiat Oncol Biol Phys. 2007;68:111–118

 Conflict of interest: none.

PII: S0360-3016(08)03722-X

doi: 10.1016/j.ijrobp.2008.10.061

International Journal of Radiation Oncology * Biology * Physics
Volume 73, Issue 3 , Pages 886-896 , 1 March 2009

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