Seminars in Radiation Oncology
Volume 17, Issue 2 , Pages 141-148 , April 2007

Future Strategies for Mitigation and Treatment of Chronic Radiation-Induced Normal Tissue Injury

  • John E. Moulder, PhD

      Affiliations

    • Corresponding Author InformationAddress reprint requests to John E. Moulder, PhD, Radiation Oncology, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226.
  • ,
  • Eric P. Cohen, MD

References 

  1. Moulder JE. Pharmacological intervention to prevent or ameliorate chronic radiation injuries. Semin Radiat Oncol. 2003;13:73–84
  2. Stone HB, McBride WH, Coleman CN. Modifying normal tissue damage postirradiation. Radiat Res. 2002;157:204–223
  3. Moulder JE. Post-irradiation approaches to treatment of radiation injuries in the context of radiological terrorism and radiation accidents: A review. Int J Radiat Biol. 2004;80:3–10
  4. Coleman CN, Blakely WF, Fike JR. Molecular and cellular biology of moderate-dose (1-10 Gy) radiation and potential mechanisms of radiation protection. Radiat Res. 2003;159:812–834
  5. Stone HB, Moulder JE, Coleman CN. Models for evaluating agents intended for the prophylaxis, mitigation and treatment of radiation injuries. Radiat Res. 2004;162:711–728
  6. Moulder JE, Fish BL, Cohen EP. ACE inhibitors and AII receptor antagonists in the treatment and prevention of bone marrow transplant nephropathy. Curr Pharm Des. 2003;9:737–749
  7. Kim JH, Brown SL, Kolozsvary A. Modification of radiation injury by Ramipril, inhibitor of angiotensin converting enzyme, on optic neuropathy in the rat. Radiat Res. 2004;161:137–142
  8. Cohen EP, Hussain S, Moulder JE. Successful treatment of radiation nephropathy with angiotensin II blockade. Int J Radiat Oncol Biol Phys. 2003;55:190–193
  9. Delanian S, Porcher R, Balla-Mekias S. Randomized, placebo-controlled trial of combined pentoxifylline and tocopherol for regression of superficial radiation-induced fibrosis. J Clin Oncol. 2003;21:2545–2550
  10. Robbins ME, Diz DI. Pathogenic role of the renin-angiotensin system in modulating radiation-induced late effects. Int J Radiat Oncol Biol Phys. 2006;64:6–12
  11. Cohen EP, Joines MM, Moulder JE: Prevention and treatment of radiation injuries—The role of the renin-angiotensin system. In Late Effects on Normal Tissues of Cancer Treatment, in Rubin P, Constine LS, Mark LB, Okunieff P (eds), Springer-Verlag, Heidelberg. (in press)
  12. Robbins MEC, Zhao W. Chronic oxidative stress and radiation-induced late normal tissue injury: A review. Int J Radiat Biol. 2004;80:251–259
  13. Langan AR, Kahn MA, Yeung IWT. Partial volume rat lung irradiation: The protective/mitigating effects of Eukarion-189, a superoxide dismutase-catalase mimetic. Radiother Oncol. 2006;92:231–238
  14. Berger ME, Christensen DM, Lowry PC. Medical management of radiation injuries: current approaches. Occup Med. 2006;56:162–172
  15. Pellmar TC, Rockwell S. Priority list of research areas for radiological nuclear threat countermeasures. Radiat Res. 2005;163:115–123
  16. Moulder JE, Fish BL, Cohen EP. Treatment of radiation nephropathy with ACE inhibitors. Int J Radiat Oncol Biol Phys. 1993;27:93–99
  17. Moulder JE, Fish BL, Cohen EP. Brief pharmacologic intervention in experimental radiation nephropathy. Radiat Res. 1998;150:535–541
  18. Moulder JE, Fish BL, Cohen EP. Noncontinuous use of angiotensin converting enzyme inhibitors in the treatment of experimental bone marrow transplant nephropathy. Bone Marrow Transplant. 1997;19:729–736
  19. Geraci JP, Sun MC, Mariano MS. Amelioration of radiation nephropathy in rats by postirradiation treatment with dexamethasone and/or captopril. Radiat Res. 1995;143:58–68
  20. Moulder JE, Robbins MEC, Cohen EP. Pharmacologic modification of radiation-induced late normal tissue injury. Cancer Treat Res. 1998;93:129–151
  21. Juncos LI, Carrasco Dueñas S, Cornejo JC. Long-term enalapril and hydrochlorothiazide in radiation nephritis. Nephron. 1993;64:249–255
  22. Ward WF, Molteni A, Ts’ao CH. Radiation pneumotoxicity in rats: Modification by inhibitors of angiotensin converting enzyme. Int J Radiat Oncol Biol Phys. 1992;22:623–625
  23. Moulder JE, Fish BL, Cohen EP. Angiotensin II receptor antagonists in the prevention of radiation nephropathy. Radiat Res. 1996;146:106–110
  24. Oikawa T, Freeman M, Lo W. Modulation of plasminogen activator inhibitor-1 in vivo: A new mechanism for the anti-fibrotic effect of renin-angiotensin inhibition. Kidney Int. 1997;51:164–172
  25. Molteni A, Moulder JE, Cohen EP. Control of radiation-induced pneumopathy and lung fibrosis by angiotensin converting enzyme inhibitors and an angiotensin II type 1 receptor blocker. Int J Radiat Biol. 2000;76:523–532
  26. Cohen EP, Fish BL, Moulder JE. The renin-angiotensin system in experimental radiation nephropathy. J Lab Clin Med. 2002;139:251–257
  27. Robbins MEC, Campling D, Rezvani M. Radiation nephropathy in mature pigs following the irradiation of both kidneys. Int J Radiat Biol. 1989;56:83–98
  28. Ward WF, Kim YT, Molteni A. Radiation-induced pulmonary endothelial dysfunction in rats: Modification by an inhibitor of angiotensin converting enzyme. Int J Radiat Oncol Biol Phys. 1988;15:135–140
  29. Cohen EP, Robbins MEC. Radiation nephropathy. Semin Nephrol. 2003;23:486–499
  30. Rosenberg ME, Smith LJ, Correa-Rotter R. The paradox of the renin-angiotensin system in chronic renal disease. Kidney Int. 1994;45:403–410
  31. Birkenhager WH, De Leeuw PW. Non-peptide angiotensin type 1 receptor antagonists in the treatment of hypertension. J Hypertens. 1999;17:873–881
  32. Siragy HM, De Gasparo M, El-Kersh M. Angiotensin-converting enzyme inhibition potentiates angiotensin II type 1 receptor effects on renal bradykinin and cGMP. Hypertension. 2001;38:183–186
  33. De Paepe B, Verstraeten VLRM, De Potter CR. Increased angiotensin II type-2 receptor density in hyperplasia, DCIS and invasive carcinoma of the breast is paralleled with increased iNOS expression. Histochem Cell Biol. 2002;117:13–19
  34. Wolf G, Wenzel U, Burns KD. Angiotensin II activates nuclear transcription factor-B through AT1 and AT2 receptors. Kidney Int. 2002;61:1986–1995
  35. Ichihara S, Senbonmatsu T, Price E. Angiotensin II type 2 receptor is essential for left ventricular hypertrophy and cardiac fibrosis in chronic angiotensin II-induced hypertension. Circulation. 2001;104:346–351
  36. Gohlke P, Pees C, Unger T. AT2 receptor stimulation increases aortic cyclic GMP in SHRSP by a kinin-dependent mechanism. Hypertension. 1998;31:349–355
  37. Moulder JE, Fish BL, Cohen EP. Impact of angiotensin II type 2 receptor blockade on experimental radiation nephropathy. Radiat Res. 2004;161:312–317
  38. Moulder JE, Fish BL, Cohen EP: Treatment of radiation nephropathy with ACE inhibitors and AII type-1 and type-2 receptor antagonists. Curr Pharm Des (in press)
  39. Moulder JE, Fish BL, Regner KR. Retinoic acid exacerbates radiation nephropathy. Radiat Res. 2002;157:199–203
  40. Moulder JE, Fish BL, Cohen EP. Dietary sodium modification and experimental radiation nephropathy. Int J Radiat Biol. 2002;79:903–911
  41. Cohen EP, Fish BL, Moulder JE. The role of nitric oxide in radiation nephropathy. Arch Physiol Biochem. 1996;104:200–206
  42. Datta PK, Moulder JE, Fish BL. TGF-β1 production in radiation nephropathy: Role of angiotensin II. Int J Radiat Biol. 1999;75:473–479
  43. Han G, Zhou YF, Zhang MS. Angelica sinensis down-regulates hydroxyproline and TGFβ1 and provides protection in mice with radiation-induced pulmonary fibrosis. Radiat Res. 2006;165:546–552
  44. Nishioka A, Ogawa Y, Mima T. Histopathologic amelioration of fibroproliferative change in rat irradiated lung using soluble transforming growth factor-beta (TGF-β) receptor mediated by adenoviral vector. Int J Radiat Oncol Biol Phys. 2004;58:1235–1241
  45. Rabbani ZN, Anscher MS, Zhang X. Soluble TGFβ type II receptor gene therapy ameliorates acute radiation-induced pulmonary injury in rats. Int J Radiat Oncol Biol Phys. 2003;57:563–572
  46. Vujaskovic Z, Groen HJM. TGF-β, radiation-induced pulmonary injury and lung cancer. Int J Radiat Biol. 2000;76:511–516
  47. Moore AF, Heiderstadt NT, Huang E. Selective inhibition of the renal angiotensin type 2 receptor increases blood pressure in conscious rats. Hypertension. 2001;37:1285–1291
  48. Zhu YC, Stauss HM, Bao G. Role of bradykinin in the antihypertensive and cardioprotective actions of converting enzyme inhibitors. Can J Physiol Pharmacol. 1995;73:827–831
  49. Araujo MC, Melo RL, Cesari MH. Peptidase specificity characterization of C- and N-terminal catalytic sites of angiotensin I-converting enzyme. Biochemistry. 2000;39:8519–8525
  50. Azizi M, Ezan E, Nicolet L. High plasma level of N-acetyl-seryl-aspartyl-lysyl-proline: A new marker of chronic angiotensin-converting enzyme inhibition. Hypertension. 1997;30:1015–1019
  51. Peng H, Carretero OA, Brigstock DR. Ac-SDKP reverses cardiac fibrosis in rats with renovascular hypertension. Hypertension. 2003;42:1164–1170
  52. Iwamoto N, Xano HJ, Yoshioka T. Acetyl-seryl-aspartyl-lysyl-proline is a novel natural cell cycle regulator of renal cells. Life Sci. 2000;66:221–226
  53. Azizi M, Rousseau A, Ezan E. Acute angiotensin-converting enzyme inhibition increases the plasma level of the natural stem cell regulator N-acetyl-seryl-aspartyl-lysyl-proline. J Clin Invest. 1996;97:839–844
  54. Delanian S, Lefaix JL. The radiation-induced fibroatrophic process: Therapeutic perspective via the antioxidant pathway. Radiother Oncol. 2004;73:119–131
  55. Brown NJ, Nakamura S, Ma L. Aldosterone modulates plasminogen activator inhibitor-1 and glomerulosclerosis in vivo. Kidney Int. 2000;58:1219–1227
  56. Jaggi JS, Seshan SV, McDevitt MR. Mitigation of radiation nephropathy after internal α-particle irradiation of kidneys. Int J Radiat Oncol Biol Phys. 2006;64:1503–1512
  57. Antignac C, Gubler MC, Leverger G. Delayed renal failure with extensive mesangiolysis following bone marrow transplantation. Kidney Int. 1989;35:1336–1344
  58. Turman MA, Hammond S, Grovas A. Possible association of retinoic acid with bone marrow transplant nephropathy. PediatrNephrol. 1999;13:755–758
  59. Fonck C, Cosyns JP, Goffin E. Glomerulopathie après radiotherapie métabolique pour insulinome métastatique. Néphrologie. 2000;21:206
  60. Raife TJ, Lager DJ. Chronic thrombotic microangiopathy associated with antineoplastic therapy with minimal hematologic effects. Mayo Clinic Proc. 2002;77:323–328
  61. Vincent F, Costa MA, Rondeau E. Chronic renal failure: A nonmalignant late effect of allogeneic stem cell transplantation. Blood. 2003;102:2695
  62. Moulder JE, Cohen EP. Radiation-induced multi-organ involvement and failure: The contribution of radiation effects on the renal system. Br J Radiol Suppl. 2005;27:82–88
  63. Ichida S, Okada K, Itoh M. Bone marrow transplant nephropathy successfully treated with angiotensin-converting enzyme inhibitor. Clin Exp Nephrol. 2006;10:78–81
  64. Bunjes D. 188Re-labeled anti-CD66 monoclonal antibody in stem cell transplantation for patients with high-risk acute myeloid leukemia. Leuk Lymphoma. 2002;43:2125–2131
  65. Haysom L, Ziegler DS, Cohn RJ. Retinoic acid may increase the risk of bone marrow transplant nephropathy. Pediatr Nephrol. 2005;20:534–538
  66. Craig JIO, Sheehan T, Bell K. The haemolytic uraemic syndrome and bone marrow transplantation. Br Med J. 1987;295:887
  67. Cruz DN, Perazella MA, Mahnensmith RL. Bone marrow transplant nephropathy: A case report and review of the literature. J Am Soc Nephrol. 1997;8:166–173
  68. Radiation Therapy Oncology Group. RTOG-0123: A Phase II Randomized Trial With Captopril in Patients Who Have Received Radiation Therapy±Chemotherapy for Stage II-IIIB Non-Small Cell Lung Cancer, Stage I Central Non-Small Cell Lung Cancer, or Limited-Stage Small Cell Lung Cancer. 2004;Philadelphia
  69. Robbins MEC, Zhao WL, Davis CS. Radiation-induced kidney injury: A role for chronic oxidative stress?. Micron. 2002;33:133–141
  70. Kang SK, Rabbani ZN, Folz RJ. Overexpression of extracellular superoxide dismutase protects mice from radiation-induced lung injury. Int J Radiat Oncol Biol Phys. 2003;57:1056–1066
  71. Vujaskovic Z, Anscher MS, Feng QF. Radiation-induced hypoxia may perpetuate late normal tissue injury. Int J Radiat Oncol Biol Phys. 2001;50:851–855
  72. Poli G, Parola M. Oxidative damage and fibrogenesis. Free Rad Biol Med. 1997;22:287–305
  73. Maier CM, Chan PH. Role of superoxide dismutases in oxidative damage and neurodegenerative disorders. Neuroscientist. 2002;8:323–334
  74. Massy ZA, Nguyen-Khoa T. Oxidative stress and chronic renal failure: Markers and management. J Nephrol. 2002;15:336–341
  75. Locatelli F, Canaud B, Eckardt KU. Oxidative stress in end-stage renal disease: An emerging threat to patient outcome. Nephrol Dial Trans. 2003;18:1272–1280
  76. Kinnula VL, Crapo JD. Superoxide dismutases in the lung and human lung diseases. Cardiovasc Res. 2003;167:1600–1619
  77. Clemens MR, Ladner C, Schmidt H. Decreased essential antioxidants and increased lipid hydroperoxides following high-dose radiochemotherapy. Free Radic Res Commun. 1989;7:227–232
  78. Arterbery VE, Pryor WA, Jiang L. Breath ethane generation during clinical total body irradiation as a marker of oxygen-free-radical-mediated lipid peroxidation: A case study. Free Radic Res Commun. 1994;17:569–576
  79. Ueda T, Toyoshima Y, Moritani TL. Protective effect of dipyridamole against lethality and lipid peroxidation in liver and spleen of the ddY mouse after whole-body irradiation. Int J Radiat Biol. 1996;69:199–204
  80. Umegaki K, Sugisawa A, Shin SJ. Different onsets of oxidative damage to DNA and lipids in bone marrow and liver in rats given total body irradiation. Free Radic Biol Med. 2001;31:1066–1074
  81. Jack CIA, Cottier B, Jackson MJ. Indicators of free radical activity in patients developing radiation pneumonitis. Int J Radiat Oncol Biol Phys. 1996;34:149–154
  82. Tofilon PJ, Fike JR. The radioresponse of the central nervous system: A dynamic process. Radiat Res. 2000;153:357–370
  83. Choi AM, Alam J. Heme oxygenase-1: Function, regulation, and implication of a novel stress-inducible protein in oxidant-induced lung injury. Am J Resp Cell Mol Biol. 1996;15:9–19
  84. Abraham NG, Kappas A. Heme oxygenase and the cardiovascular-renal system. Free Radic Biol Med. 2005;39:1–25
  85. Datta PK, Moulder JE, Fish BL. Induction of heme oxygenase-1 in radiation nephropathy: Role of angiotensin. Radiat Res. 2001;155:734–739
  86. Carpenter M, Epperly MW, Agarwal A. Inhalation delivery of manganese superoxide dismutase-plasmid/liposomes protects the murine lung from irradiation damage. Gene Ther. 2005;12:685–693
  87. Greenberger JS, Epperly MW, Gretton J. Radioprotective gene therapy. Curr Gene Ther. 2003;3:183–195
  88. Rabbani ZN, Anscher MS, Folz RJ. Overexpression of extracellular superoxide dismutase reduces acute radiation induced lung toxicity. BMC Cancer. 2005;5:59
  89. Doctrow SR, Baudry M, Huffman K. Salen Mn complexes: Multifunctional catalytic antioxidants protective in models for neurodegenerative diseases of aging. In:  Sessler JL,  Doctrow SR,  McMurray JT editor. Medicinal Inorganic Chemistry. New York: American Chemical Society; 2004;p. 319–347
  90. Lefaix JL, Delanian S, Leplat JJ. Successful treatment of radiation-induced fibrosis using Cu/Zn-SOD and Mn-SOD: An experimental study. Int J Radiat Oncol Biol Phys. 1996;35:305–312
  91. Delanian S, Baillet F, Huart J. Successful treatment of radiation-induced fibrosis using liposomal Cu/Zn superoxide dismutase: Clinical trial. Radiother Oncol. 1994;32:12–20
  92. Lefaix JL, Delanian S, Vozenin MC. Striking regression of subcutaneous fibrosis induced by high doses of gamma rays using a combination of pentoxifylline and α-tocopherol: An experimental study. Int J Radiat Oncol Biol Phys. 1999;43:839–847
  93. Delanian S. Striking regression of radiation-induced fibrosis by a combination of pentoxifylline and tocopherol. Br J Radiol. 1998;71:892–894
  94. Food and Drug Administration. New drug and biological drug products: evidence needed to demonstrate effectiveness of new drugs when human efficacy studies are not ethical or feasible. Fed Regist. 2002;67:37988–37998
  95. Food and Drug Administration. Good laboratory practice for non-clinical laboratory studies (21 Code of Federal Register Part 58). 2002;

PII: S1053-4296(06)00111-1

doi: 10.1016/j.semradonc.2006.11.010

Seminars in Radiation Oncology
Volume 17, Issue 2 , Pages 141-148 , April 2007