Chemical and biological basis for development of novel radioprotective drugs for cancer therapy

References

• Islam MT. Radiation interactions with biological systems. Int J Radiat Biol. 2017;93(5):487–493.
   PubMed Web of Science ®Google Scholar
• Mavragani IV, Nikitaki Z, Kalospyros SA, et al. Ionizing radiation and complex DNA damage: from prediction to detection challenges and biological significance. Cancers (Basel). 2019;11(11):1789.
   Web of Science ®Google Scholar
• O'Neill P, Wardman P. Radiation chemistry comes before radiation biology. Int J Radiat Biol. 2009;85(1):9–25.
   PubMed Web of Science ®Google Scholar
• Willers H, Dahm-Daphi J, Powell SN. Repair of radiation damage to DNA. Br J Cancer. 2004;90(7):1297–1301.
   PubMed Web of Science ®Google Scholar
• Rosen EM, Day R, Singh VK. New approaches to radiation protection. Front Oncol. 2014;4:381.
   PubMed Web of Science ®Google Scholar
• Ringborg U, Bergqvist D, Brorsson B, et al. The Swedish Council on Technology Assessment in Health Care (SBU) systematic overview of radiotherapy for cancer including a prospective survey of radiotherapy practice in Sweden 2001-summary and conclusions. Acta Oncol. 2003;42(5-6):357–365.
   PubMed Web of Science ®Google Scholar
• Berrington de Gonzalez A, Gilbert E, Curtis R, et al. Second solid cancers after radiation therapy: a systematic review of the epidemiologic studies of the radiation dose-response relationship. Int J Radiat Oncol Biol Phys. 2013;86(2):224–233.
   PubMed Web of Science ®Google Scholar
• Citrin DE. Recent developments in radiotherapy. N Engl J Med. 2017;377(22):2200–2201.
   PubMed Web of Science ®Google Scholar
• Saenger EL. Radiation accidents. Ann Emerg Med. 1986;15(9):1061–1066.
   PubMed Web of Science ®Google Scholar
• Miller KL. The nuclear reactor accident at Three Mile Island. Radiographics. 1994;14(1):215–224.
   PubMed Web of Science ®Google Scholar
• Goldman M. The Russian radiation legacy: its integrated impact and lessons. Environ Health Perspect. 1997;105(Suppl 6):1385–1391.
   PubMed Web of Science ®Google Scholar
• Vasin MV. Comments on the mechanisms of action of radiation protective agents: basis components and their polyvalence. Springerplus. 2014;3:414.
   PubMed Web of Science ®Google Scholar
• Weiss JF, Landauer MR. History and development of radiation-protective agents. Int J Radiat Biol. 2009;85(7):539–573.
   PubMed Web of Science ®Google Scholar
• Phillips TL. Rationale for initial clinical trials and future development of radioprotectors. Cancer Clin Trials. 1980;3(2):165–173.
   PubMedGoogle Scholar
• Reisz JA, Bansal N, Qian J, et al. Effects of ionizing radiation on biological molecules-mechanisms of damage and emerging methods of detection. Antioxid Redox Signal. 2014;21(2):260–292.
   PubMed Web of Science ®Google Scholar
• Salganik RI. The benefits and hazards of antioxidants: controlling apoptosis and other protective mechanisms in cancer patients and the human population. J Am Coll Nutr. 2001;20(5 Suppl):464S–472S. discussion 473S-475S.
   PubMed Web of Science ®Google Scholar
• McClain DE, Kalinich JF, Ramakrishnan N. Trolox inhibits apoptosis in irradiated MOLT-4 lymphocytes. Faseb J. 1995;9(13):1345–1354.
   PubMed Web of Science ®Google Scholar
• Patt HM, Tyree EB, Straube RL, et al. Cysteine protection against X irradiation. Science. 1949;110(2852):213–214.
   PubMed Web of Science ®Google Scholar
• Limoli CL, Kaplan MI, Giedzinski E, et al. Attenuation of radiation-induced genomic instability by free radical scavengers and cellular proliferation. Free Radic Biol Med. 2001;31(1):10–19.
   PubMed Web of Science ®Google Scholar
• Jensen GL, Meister A. Radioprotection of human lymphoid cells by exogenously supplied glutathione is mediated by gamma-glutamyl transpeptidase. Proc Natl Acad Sci USA. 1983;80(15):4714–4717.
   PubMed Web of Science ®Google Scholar
• Wellner VP, Anderson ME, Puri RN, et al. Radioprotection by glutathione ester: transport of glutathione ester into human lymphoid cells and fibroblasts. Proc Natl Acad Sci USA. 1984;81(15):4732–4735.
   PubMed Web of Science ®Google Scholar
• el-Nahas SM, Mattar FE, Mohamed AA. Radioprotective effect of vitamins C and E. Mutat Res. 1993;301(2):143–147.
   PubMed Web of Science ®Google Scholar
• Neal R, Matthews RH, Lutz P, et al. Antioxidant role of N-acetyl cysteine isomers following high dose irradiation. Free Radic Biol Med. 2003;34(6):689–695.
   PubMed Web of Science ®Google Scholar
• Ainsworth EJ. From endotoxins to newer immunomodulators: survival-promoting effects of microbial polysaccharide complexes in irradiated animals. Pharmacol Ther. 1988;39(1-3):223–241.
   PubMed Web of Science ®Google Scholar
• Sorenson JR. Essential metalloelement metabolism and radiation protection and recovery. Radiat Res. 1992;132(1):19–29.
   PubMed Web of Science ®Google Scholar
• Seifter E, Rettura G, Padawer J, et al. Morbidity and mortality reduction by supplemental vitamin A or beta-carotene in CBA mice given total-body gamma-radiation. J Natl Cancer Inst. 1984;73(5):1167–1177.
   PubMedGoogle Scholar
• Weiss JF, Kumar KS, Walden TL, et al. Advances in radioprotection through the use of combined agent regimens. Int J Radiat Biol. 1990;57(4):709–722.
   PubMed Web of Science ®Google Scholar
• Weiss JF, Srinivasan V, Kumar KS, et al. Radioprotection by metals: selenium. Adv Space Res. 1992;12(2-3):223–231.
   PubMedGoogle Scholar
• Abou-Seif MA, El-Naggar MM, El-Far M, et al. Amelioration of radiation-induced oxidative stress and biochemical alteration by SOD model compounds in pre-treated gamma-irradiated rats. Clin Chim Acta. 2003;337(1-2):23–33.
   PubMed Web of Science ®Google Scholar
• Uma Devi P, Ganasoundari A, Rao BS, et al. In vivo radioprotection by ocimum flavonoids: survival of mice. Radiat Res. 1999;151(1):74–78.
   PubMed Web of Science ®Google Scholar
• Emerit I, Oganesian N, Sarkisian T, et al. Clastogenic factors in the plasma of Chernobyl accident recovery workers: anticlastogenic effect of Ginkgo biloba extract. Radiat Res. 1995;144(2):198–205.
   PubMed Web of Science ®Google Scholar
• Emerit I, Oganesian N, Arutyunian R, et al. Oxidative stress-related clastogenic factors in plasma from Chernobyl liquidators: protective effects of antioxidant plant phenols, vitamins and oligoelements. Mutat Res. 1997;377(2):239–246.
   PubMed Web of Science ®Google Scholar
• George KC, Hebbar SA, Kale SP, et al. Caffeine protects mice against whole-body lethal dose of gamma-irradiation. J Radiol Prot. 1999;19(2):171–176.
   PubMedGoogle Scholar
• Dion MW, Hussey DH, Osborne JW. The effect of pentoxifylline on early and late radiation injury following fractionated irradiation in C3H mice. Int J Radiat Oncol Biol Phys. 1989;17(1):101–107.
   PubMed Web of Science ®Google Scholar
• Ueda T, Toyoshima Y, Moritani T, et al. 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(2):199–204.
   PubMed Web of Science ®Google Scholar
• Davis TA, Mungunsukh O, Zins S, et al. Genistein induces radioprotection by hematopoietic stem cell quiescence. Int J Radiat Biol. 2008;84(9):713–726.
   PubMed Web of Science ®Google Scholar
• Pal S, Saha C, Dey SK. Studies on black tea (Camellia sinensis) extract as a potential antioxidant and a probable radioprotector. Radiat Environ Biophys. 2013;52(2):269–278.
   PubMed Web of Science ®Google Scholar
• Nagaprashantha LD, Vatsyayan R, Singhal J, et al. Anti-cancer effects of novel flavonoid vicenin-2 as a single agent and in synergistic combination with docetaxel in prostate cancer. Biochem Pharmacol. 2011;82(9):1100–1109.
   PubMed Web of Science ®Google Scholar
• Epperly MW, Wang H, Jones JA, et al. Antioxidant-chemoprevention diet ameliorates late effects of total-body irradiation and supplements radioprotection by MnSOD-plasmid liposome administration. Radiat Res. 2011;175(6):759–765.
   PubMed Web of Science ®Google Scholar
• Bacq ZM. The amines and particularly cysteamine as protectors against roentgen rays. Acta Radiol. 1954;41(1):47–55.
   PubMed Web of Science ®Google Scholar
• Mikaelsen K. The protective effect of glutathione against radiation-induced chromosome aberrations. Science. 1952;116(3007):172–174.
   PubMed Web of Science ®Google Scholar
• Mittler S. The failure of sulphhydryl compounds, AET, MEA, and glutathione to protect against X-ray induced chromosome aberrations in male drosophila. Int J Radiat Biol Relat Stud Phys Chem Med. 1964;8:405–413.
   PubMed Web of Science ®Google Scholar
• Brown DQ, Graham WJ, MacKenzie LJ, et al. Can WR-2721 be improved upon? Pharmacol Ther. 1988;39(1-3):157–168.
   PubMed Web of Science ®Google Scholar
• Antonadou D, Pepelassi M, Synodinou M, et al. Prophylactic use of amifostine to prevent radiochemotherapy-induced mucositis and xerostomia in head-and-neck cancer. Int J Radiat Oncol Biol Phys. 2002;52(3):739–747.
   PubMed Web of Science ®Google Scholar
• Brizel DM, Wasserman TH, Henke M, et al. and others. Phase III randomized trial of amifostine as a radioprotector in head and neck cancer. J Clin Oncol. 2000;18(19):3339–3345.
   PubMed Web of Science ®Google Scholar
• 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(1):111–118.
   PubMed Web of Science ®Google Scholar
• Shaw LM, Bonner HS, Schuchter L, et al. Pharmacokinetics of amifostine: effects of dose and method of administration. Semin Oncol. 1999;26(2 Suppl 7):34–36.
   PubMed Web of Science ®Google Scholar
• Durand RE, Olive PL. Radiosensitisation and radioprotection by BSO and WR-2721: the role of oxygenation. Br J Cancer. 1989;60(4):517–522.
   PubMed Web of Science ®Google Scholar
• Durand RE. Radioprotection by WR-2721 in vitro at low oxygen tensions: implications for its mechanisms of action. Br J Cancer. 1983;47(3):387–392.
   PubMed Web of Science ®Google Scholar
• Savoye C, Swenberg C, Hugot S, et al. Thiol WR-1065 and disulphide WR-33278, two metabolites of the drug ethyol (WR-2721), protect DNA against fast neutron-induced strand breakage. Int J Radiat Biol. 1997;71(2):193–202.
   PubMed Web of Science ®Google Scholar
• Hensley ML, Hagerty KL, Kewalramani T, et al. American Society of Clinical Oncology 2008 clinical practice guideline update: use of chemotherapy and radiation therapy protectants. J Clin Oncol. 2009;27(1):127–145.
   PubMed Web of Science ®Google Scholar
• Copp RR, Peebles DD, Soref CM, et al. Radioprotective efficacy and toxicity of a new family of aminothiol analogs. Int J Radiat Biol. 2013;89(7):485–492.
   PubMed Web of Science ®Google Scholar
• Uma Devi P, Thomas B. Bone marrow cell protection and modification of drug toxicity by combination of protectors. Pharmacol Ther. 1988;39(1-3):213–214.
   PubMed Web of Science ®Google Scholar
• Kilciksiz S, Demirel C, Erdal N, et al. The effect of N-acetylcysteine on biomarkers for radiation-induced oxidative damage in a rat model. Acta Med Okayama. 2008;62(6):403–409.
   PubMed Web of Science ®Google Scholar
• Wu W, Abraham L, Ogony J, et al. Effects of N-acetylcysteine amide (NACA), a thiol antioxidant on radiation-induced cytotoxicity in Chinese hamster ovary cells. Life Sci. 2008;82(21-22):1122–1130.
   PubMed Web of Science ®Google Scholar
• Shirazi A, Ghobadi G, Ghazi-Khansari M. A radiobiological review on melatonin: a novel radioprotector. J Radiat Res. 2007;48(4):263–272.
   PubMed Web of Science ®Google Scholar
• Poeggeler B, Saarela S, Reiter RJ, et al. Melatonin-a highly potent endogenous radical scavenger and electron donor: new aspects of the oxidation chemistry of this indole accessed in vitro. Ann N Y Acad Sci. 1994;738:419–420.
   PubMed Web of Science ®Google Scholar
• Vijayalaxmi, Reiter RJ, Meltz ML. Melatonin protects human blood lymphocytes from radiation-induced chromosome damage. Mutat Res. 1995;346(1):23–31.
   PubMed Web of Science ®Google Scholar
• Vijayalaxmi, Reiter RJ, Herman TS, Meltz ML. Melatonin and radioprotection from genetic damage: in vivo/in vitro studies with human volunteers. Mutat Res. 1996;371(3-4):221–228.
   PubMed Web of Science ®Google Scholar
• Das B, Bennett PV, Cutter NC, et al. Melatonin protects human cells from clustered DNA damages, killing and acquisition of soft agar growth induced by X-rays or 970 MeV/n Fe ions. Int J Radiat Biol. 2011;87(6):545–555.
   PubMed Web of Science ®Google Scholar
• Blickenstaff RT, Brandstadter SM, Reddy S, et al. Potential radioprotective agents. 1. Homologs of melatonin. J Pharm Sci. 1994;83(2):216–218.
   PubMed Web of Science ®Google Scholar
• Vijayalaxmi Meltz ML, Reiter RJ, Herman TS, et al. Melatonin and protection from whole-body irradiation: survival studies in mice. Mutat Res. 1999;425(1):21–27.
   PubMed Web of Science ®Google Scholar
• Karbownik M, Reiter RJ. Melatonin protects against oxidative stress caused by delta-aminolevulinic acid: implications for cancer reduction. Cancer Invest. 2002;20(2):276–286.
   PubMed Web of Science ®Google Scholar
• Karbownik M, Reiter RJ, Qi W, et al. Protective effects of melatonin against oxidation of guanine bases in DNA and decreased microsomal membrane fluidity in rat liver induced by whole body ionizing radiation. Mol Cell Biochem. 2000;211(1-2):137–144.
   PubMed Web of Science ®Google Scholar
• Tan DX, Manchester LC, Burkhardt S, et al. N1-acetyl-N2-formyl-5-methoxykynuramine, a biogenic amine and melatonin metabolite, functions as a potent antioxidant. Faseb J. 2001;15(12):2294–2296.
   PubMed Web of Science ®Google Scholar
• Manda K, Ueno M, Anzai K. AFMK, a melatonin metabolite, attenuates X-ray-induced oxidative damage to DNA, proteins and lipids in mice. J Pineal Res. 2007;42(4):386–393.
   PubMed Web of Science ®Google Scholar
• Niu Y, Wang H, Wiktor-Brown D, et al. Irradiated esophageal cells are protected from radiation-induced recombination by MnSOD gene therapy. Radiat Res. 2010;173(4):453–461.
   PubMed Web of Science ®Google Scholar
• Epperly MW, Dixon T, Wang H, et al. Modulation of radiation-induced life shortening by systemic intravenous MnSOD-plasmid liposome gene therapy. Radiat Res. 2008;170(4):437–443.
   PubMed Web of Science ®Google Scholar
• Lee JH, Park JW. A manganese porphyrin complex is a novel radiation protector. Free Radic Biol Med. 2004;37(2):272–283.
   PubMed Web of Science ®Google Scholar
• Li H, Wang Y, Pazhanisamy SK, et al. Mn(III) meso-tetrakis-(N-ethylpyridinium-2-yl) porphyrin mitigates total body irradiation-induced long-term bone marrow suppression. Free Radic Biol Med. 2011;51(1):30–37.
   PubMed Web of Science ®Google Scholar
• Rabbani ZN, Salahuddin FK, Yarmolenko P, et al. Low molecular weight catalytic metalloporphyrin antioxidant AEOL 10150 protects lungs from fractionated radiation. Free Radic Res. 2007;41(11):1273–1282.
   PubMed Web of Science ®Google Scholar
• Jaramillo MC, Frye JB, Crapo JD, et al. Increased manganese superoxide dismutase expression or treatment with manganese porphyrin potentiates dexamethasone-induced apoptosis in lymphoma cells. Cancer Res. 2009;69(13):5450–5457.
   PubMed Web of Science ®Google Scholar
• Liu JF, Wang X, Tan HN, et al. Effect of heparin-superoxide dismutase on γ-radiation induced DNA damage in vitro and in vivo. Drug Discov Ther. 2010;4(5):355–361.
   PubMedGoogle Scholar
• Pollard JM, Reboucas JS, Durazo A, et al. Radioprotective effects of manganese-containing superoxide dismutase mimics on ataxia-telangiectasia cells. Free Radic Biol Med. 2009;47(3):250–260.
   PubMed Web of Science ®Google Scholar
• Rosenthal RA, Fish B, Hill RP, et al. Salen Mn complexes mitigate radiation injury in normal tissues. Anticancer Agents Med Chem. 2011;11(4):359–372.
   PubMed Web of Science ®Google Scholar
• Mitchell JB, Samuni A, Krishna MC, et al. Biologically active metal-independent superoxide dismutase mimics. Biochemistry. 1990;29(11):2802–2807.
   PubMed Web of Science ®Google Scholar
• Samuni A, Winkelsberg D, Pinson A, et al. Nitroxide stable radicals protect beating cardiomyocytes against oxidative damage. J Clin Invest. 1991;87(5):1526–1530.
   PubMed Web of Science ®Google Scholar
• Krishna MC, Grahame DA, Samuni A, et al. Oxoammonium cation intermediate in the nitroxide-catalyzed dismutation of superoxide. Proc Natl Acad Sci USA. 1992;89(12):5537–5541.
   PubMed Web of Science ®Google Scholar
• Hahn SM, Tochner Z, Krishna CM, et al. Tempol, a stable free radical, is a novel murine radiation protector. Cancer Res. 1992;52(7):1750–1753.
   PubMed Web of Science ®Google Scholar
• Cotrim AP, Hyodo F, Matsumoto K, et al. Differential radiation protection of salivary glands versus tumor by Tempol with accompanying tissue assessment of Tempol by magnetic resonance imaging. Clin Cancer Res. 2007;13(16):4928–4933.
   PubMed Web of Science ®Google Scholar
• Jiang J, Belikova NA, Hoye AT, et al. A mitochondria-targeted nitroxide/hemigramicidin S conjugate protects mouse embryonic cells against gamma irradiation. Int J Radiat Oncol Biol Phys. 2008;70(3):816–825.
   PubMed Web of Science ®Google Scholar
• Gokhale A, Rwigema JC, Epperly MW, et al. Small molecule GS-nitroxide ameliorates ionizing irradiation-induced delay in bone wound healing in a novel murine model. In Vivo. 2010;24(4):377–385.
   PubMed Web of Science ®Google Scholar
• Rajagopalan MS, Gupta K, Epperly MW, et al. Kagan VE and others. The mitochondria-targeted nitroxide JP4-039 augments potentially lethal irradiation damage repair. In Vivo. 2009;23(5):717–726.
   PubMed Web of Science ®Google Scholar
• Epperly MW, Goff JP, Li S, et al. Intraesophageal administration of GS-nitroxide (JP4-039) protects against ionizing irradiation-induced esophagitis. In Vivo. 2010;24(6):811–819.
   PubMed Web of Science ®Google Scholar
• Goff JP, Epperly MW, Dixon T, et al. Radiobiologic effects of GS-nitroxide (JP4-039) on the hematopoietic syndrome. In Vivo. 2011;25(3):315–323.
   PubMed Web of Science ®Google Scholar
• Ohsawa I, Ishikawa M, Takahashi K, et al. Hydrogen acts as a therapeutic antioxidant by selectively reducing cytotoxic oxygen radicals. Nat Med. 2007;13(6):688–694.
   PubMed Web of Science ®Google Scholar
• Qian L, Cao F, Cui J, et al. Radioprotective effect of hydrogen in cultured cells and mice. Free Radic Res. 2010;44(3):275–282.
   PubMed Web of Science ®Google Scholar
• Chuai Y, Shen J, Qian L, et al. Hydrogen-rich saline protects spermatogenesis and hematopoiesis in irradiated BALB/c mice. Med Sci Monit. 2012;18(3):BR89–94.
   PubMed Web of Science ®Google Scholar
• Qian L, Cao F, Cui J, et al. The potential cardioprotective effects of hydrogen in irradiated mice. J Radiat Res. 2010;51(6):741–747.
   PubMed Web of Science ®Google Scholar
• Smith PJ, Anderson CO. Modification of the radiation sensitivity of human tumour cells by a bis-benzimidazole derivative. Int J Radiat Biol Relat Stud Phys Chem Med. 1984;46(4):331–344.
   PubMed Web of Science ®Google Scholar
• Martin RF, Broadhurst S, D'Abrew S, et al. Radioprotection by DNA ligands. Br J Cancer Suppl. 1996;27:S99–S101.
   PubMedGoogle Scholar
• Martin RF, Broadhurst S, Reum ME, et al. In vitro studies with methylproamine: a potent new radioprotector. Cancer Res. 2004;64(3):1067–1070.
   PubMed Web of Science ®Google Scholar
• Mishra K, Bhardwaj R, Chaudhury NK. Netropsin, a minor groove binding ligand: a potential radioprotective agent. Radiat Res. 2009;172(6):698–705.
   PubMed Web of Science ®Google Scholar
• Zoidis E, Seremelis I, Kontopoulos N, et al. Selenium-dependent antioxidant enzymes: actions and properties of selenoproteins. Antioxidants (Basel). 2018;7(5):66.
   PubMedGoogle Scholar
• Tak JK, Park JW. The use of ebselen for radioprotection in cultured cells and mice. Free Radic Biol Med. 2009;46(8):1177–1185.
   PubMed Web of Science ®Google Scholar
• Kunwar A, Bansal P, Kumar SJ, et al. Unnikrishnan MK and others. In vivo radioprotection studies of 3,3'-diselenodipropionic acid, a selenocystine derivative. Free Radic Biol Med. 2010;48(3):399–410.
   PubMed Web of Science ®Google Scholar
• Miller LL, Neta R. Therapeutic utility of cytokines in counteracting the bone marrow suppression of radio- and chemo-therapy. In: Gearing A, Rossio J, Oppenheim JJ, editors. Clinical applications of cytokines: role in pathogenesis, diagnosis and therapy. Vol 225. New York: Oxford University Press; 1993.
   Google Scholar
• Neta R. Cytokines in radioprotection and therapy of radiation injury. Biotherapy. 1988;1(1):41–45.
   PubMedGoogle Scholar
• Farese AM, Williams DE, Seiler FR, et al. Combination protocols of cytokine therapy with interleukin-3 and granulocyte-macrophage colony-stimulating factor in a primate model of radiation-induced marrow aplasia. Blood. 1993;82(10):3012–3018.
   PubMed Web of Science ®Google Scholar
• MacVittie TJ, Farese AM, Patchen ML, et al. Therapeutic efficacy of recombinant interleukin-6 (IL-6) alone and combined with recombinant human IL-3 in a nonhuman primate model of high-dose, sublethal radiation-induced marrow aplasia. Blood. 1994;84(8):2515–2522.
   PubMed Web of Science ®Google Scholar
• Patchen ML, MacVittie TJ, Williams JL, Schwartz GN, et al. Administration of interleukin-6 stimulates multilineage hematopoiesis and accelerates recovery from radiation-induced hematopoietic depression. Blood. 1991;77(3):472–480.
   PubMed Web of Science ®Google Scholar
• Bolotin E, Smogorzewska M, Smith S, et al. Enhancement of thymopoiesis after bone marrow transplant by in vivo interleukin-7. Blood. 1996;88(5):1887–1894.
   PubMed Web of Science ®Google Scholar
• Redlich CA, Gao X, Rockwell S, et al. IL-11 enhances survival and decreases TNF production after radiation-induced thoracic injury. J Immunol. 1996;157(4):1705–1710.
   PubMed Web of Science ®Google Scholar
• Neta R, Stiefel SM, Finkelman F, et al. IL-12 protects bone marrow from and sensitizes intestinal tract to ionizing radiation. J Immunol. 1994;153(9):4230–4237.
   PubMed Web of Science ®Google Scholar
• Neta R, Vogel SN, Plocinski JM, et al. In vivo modulation with anti-interleukin-1 (IL-1) receptor (p80) antibody 35F5 of the response to IL-1. The relationship of radioprotection, colony-stimulating factor, and IL-6. Blood. 1990;76(1):57–62.
   PubMed Web of Science ®Google Scholar
• Neta R, Oppenheim JJ, Douches SD. Interdependence of the radioprotective effects of human recombinant interleukin 1 alpha, tumor necrosis factor alpha, granulocyte colony-stimulating factor, and murine recombinant granulocyte-macrophage colony-stimulating factor. J Immunol. 1988;140(1):108–111.
   PubMed Web of Science ®Google Scholar
• Vacek A, Tacev T, Hofer M. Modulation of radioprotective effects of respiratory hypoxia by changing the duration of hypoxia before irradiation and by combining hypoxia and administration of hemopoiesis-stimulating agents. Strahlenther Onkol. 2001;177(9):474–481.
   PubMed Web of Science ®Google Scholar
• Farese AM, Hunt P, Grab LB, et al. Combined administration of recombinant human megakaryocyte growth and development factor and granulocyte colony-stimulating factor enhances multilineage hematopoietic reconstitution in nonhuman primates after radiation-induced marrow aplasia. J Clin Invest. 1996;97(9):2145–2151.
   PubMed Web of Science ®Google Scholar
• Hokom MM, Lacey D, Kinstler OB, et al. Grasel T and others. Pegylated megakaryocyte growth and development factor abrogates the lethal thrombocytopenia associated with carboplatin and irradiation in mice. Blood. 1995;86(12):4486–4492.
   PubMed Web of Science ®Google Scholar
• Singh VK, Yadav VS. Role of cytokines and growth factors in radioprotection. Exp Mol Pathol. 2005;78(2):156–169.
   PubMed Web of Science ®Google Scholar
• MacVittie TJ, Farese AM, Herodin F, et al. Combination therapy for radiation-induced bone marrow aplasia in nonhuman primates using synthokine SC-55494 and recombinant human granulocyte colony-stimulating factor. Blood. 1996;87(10):4129–4135.
   PubMed Web of Science ®Google Scholar
• Boraschi D, Nencioni L, Villa L, et al. In vivo stimulation and restoration of the immune response by the noninflammatory fragment 163-171 of human interleukin 1 beta. J Exp Med. 1988;168(2):675–686.
   PubMed Web of Science ®Google Scholar
• Williams DE, Dunn JT, Park LS, et al. A GM-CSF/IL-3 fusion protein promotes neutrophil and platelet recovery in sublethally irradiated rhesus monkeys. Biotechnol Ther. 1993;4(1-2):17–29.
   PubMedGoogle Scholar
• Neta R, Vogel SN, Oppenheim JJ, et al. Cytokines in radioprotection. Comparison of the radioprotective effects of IL-1 to IL-2, GM-CSF and IFN gamma. Lymphokine Res. 1986;5 (Suppl 1):S105–S10.
   PubMedGoogle Scholar
• Neta R, Oppenheim JJ. Radioprotection with cytokines: a clarification of terminology. Cancer Cells. 1991;3(11):457.
   PubMed Web of Science ®Google Scholar
• Neta R. Modulation with cytokines of radiation injury: suggested mechanisms of action. Environ Health Perspect. 1997;105(Suppl 6):1463–1465.
   PubMed Web of Science ®Google Scholar
• Okunieff P, Wu T, Huang K, et al. Differential radioprotection of three mouse strains by basic or acidic fibroblast growth factor. Br J Cancer Suppl. 1996;27:S105–S8.
   PubMedGoogle Scholar
• Wilkins HR, Ohneda K, Keku TO, et al. Reduction of spontaneous and irradiation-induced apoptosis in small intestine of IGF-I transgenic mice. Am J Physiol Gastrointest Liver Physiol. 2002;283(2):G457–64.
   PubMed Web of Science ®Google Scholar
• Qiu W, Leibowitz B, Zhang L, et al. Growth factors protect intestinal stem cells from radiation-induced apoptosis by suppressing PUMA through the PI3K/AKT/p53 axis. Oncogene. 2010;29(11):1622–1632.
   PubMed Web of Science ®Google Scholar
• Farrell CL, Bready JV, Rex KL, et al. Starnes CO and others. Keratinocyte growth factor protects mice from chemotherapy and radiation-induced gastrointestinal injury and mortality. Cancer Res. 1998;58(5):933–939.
   PubMed Web of Science ®Google Scholar
• Gratwohl A, John L, Baldomero H, et al. Wodnar-Filipowicz A. FLT-3 ligand provides hematopoietic protection from total body irradiation in rabbits. Blood. 1998;92(3):765–769.
   PubMed Web of Science ®Google Scholar
• Oh H, Seong J, Kim W, et al. Recombinant human epidermal growth factor (rhEGF) protects radiation-induced intestine injury in murine system. J Radiat Res. 2010;51(5):535–541.
   PubMed Web of Science ®Google Scholar
• Hoesel B, Schmid JA. The complexity of NF-κB signaling in inflammation and cancer. Mol Cancer. 2013;12:86.
   PubMed Web of Science ®Google Scholar
• Ainsworth EJ, Hatch MH. The effect of Proteus morganii endotoxin on radiation mortality in mice. Radiat Res. 1960;13:632–638.
   PubMed Web of Science ®Google Scholar
• Pratt AG, Emerson RJ, Levin S, et al. Granulocytic recovery in the polycythemic dog treated with endotoxin postirradiation. Radiat Res. 1973;56(1):162–170.
   PubMed Web of Science ®Google Scholar
• Burdelya LG, Krivokrysenko VI, Tallant TC, et al. An agonist of toll-like receptor 5 has radioprotective activity in mouse and primate models. Science. 2008;320(5873):226–230.
   PubMed Web of Science ®Google Scholar
• Singh VK, Ducey EJ, Fatanmi OO, et al. CBLB613: a TLR 2/6 agonist, natural lipopeptide of Mycoplasma arginini , as a novel radiation countermeasure. Radiat Res. 2012;177(5):628–642.
   PubMed Web of Science ®Google Scholar
• Egan LJ, Eckmann L, Greten FR, et al. IkappaB-kinasebeta-dependent NF-kappaB activation provides radioprotection to the intestinal epithelium. Proc Natl Acad Sci USA. 2004;101(8):2452–2457.
   PubMed Web of Science ®Google Scholar
• Riehl T, Cohn S, Tessner T, et al. Lipopolysaccharide is radioprotective in the mouse intestine through a prostaglandin-mediated mechanism. Gastroenterology. 2000;118(6):1106–1116.
   PubMed Web of Science ®Google Scholar
• Bogojević D, Poznanović G, Grdović N, et al. Administration of rat acute-phase protein α(2)-macroglobulin before total-body irradiation initiates cytoprotective mechanisms in the liver. Radiat Environ Biophys. 2011;50(1):167–179.
   PubMed Web of Science ®Google Scholar
• Moi P, Chan K, Asunis I, et al. Isolation of NF-E2-related factor 2 (Nrf2), a NF-E2-like basic leucine zipper transcriptional activator that binds to the tandem NF-E2/AP1 repeat of the beta-globin locus control region. Proc Natl Acad Sci USA. 1994;91(21):9926–9930.
   PubMed Web of Science ®Google Scholar
• Rangasamy T, Cho CY, Thimmulappa RK, et al. Genetic ablation of Nrf2 enhances susceptibility to cigarette smoke-induced emphysema in mice. J Clin Invest. 2004;114(9):1248–1259.
   PubMed Web of Science ®Google Scholar
• Travis EL, Rachakonda G, Zhou X, et al. NRF2 deficiency reduces life span of mice administered thoracic irradiation. Free Radic Biol Med. 2011;51(6):1175–1183.
   PubMed Web of Science ®Google Scholar
• Kensler TW, Wakabayashi N, Biswal S. Cell survival responses to environmental stresses via the Keap1-Nrf2-ARE pathway. Annu Rev Pharmacol Toxicol. 2007;47:89–116.
   PubMed Web of Science ®Google Scholar
• McDonald JT, Kim K, Norris AJ, et al. Ionizing radiation activates the Nrf2 antioxidant response. Cancer Res. 2010;70(21):8886–8895.
   PubMed Web of Science ®Google Scholar
• Singh A, Bodas M, Wakabayashi N, et al. Gain of Nrf2 function in non-small-cell lung cancer cells confers radioresistance. Antioxid Redox Signal. 2010;13(11):1627–1637.
   PubMed Web of Science ®Google Scholar
• Eskiocak U, Kim SB, Roig AI, et al. CDDO-Me protects against space radiation-induced transformation of human colon epithelial cells. Radiat Res. 2010;174(1):27–36.
   PubMed Web of Science ®Google Scholar
• Kim SB, Pandita RK, Eskiocak U, et al. Targeting of Nrf2 induces DNA damage signaling and protects colonic epithelial cells from ionizing radiation. Proc Natl Acad Sci USA. 2012;109(43):E2949–55.
   PubMed Web of Science ®Google Scholar
• Bai H, Liu R, Chen HL, Zhang W, et al. Enhanced antioxidant effect of caffeic acid phenethyl ester and Trolox in combination against radiation induced-oxidative stress. Chem Biol Interact. 2014;207:7–15.
   PubMed Web of Science ®Google Scholar
• Patwardhan RS, Sharma D, Checker R, Sandur SK. Mitigation of radiation-induced hematopoietic injury via regulation of cellular MAPK/phosphatase levels and increasing hematopoietic stem cells. Free Radic Biol Med. 2014;68:52–64.
   PubMed Web of Science ®Google Scholar
• Khan NM, Sandur SK, Checker R, et al. Pro-oxidants ameliorate radiation-induced apoptosis through activation of the calcium-ERK1/2-Nrf2 pathway. Free Radic Biol Med. 2011;51(1):115–128.
   PubMed Web of Science ®Google Scholar
• Tsai JJ, Dudakov JA, Takahashi K, et al. Nrf2 regulates haematopoietic stem cell function. Nat Cell Biol. 2013;15(3):309–316.
   PubMed Web of Science ®Google Scholar
• Kim JH, Thimmulappa RK, Kumar V, et al. NRF2-mediated Notch pathway activation enhances hematopoietic reconstitution following myelosuppressive radiation. J Clin Invest. 2014;124(2):730–741.
   PubMed Web of Science ®Google Scholar
• Ayrapetov MK, Xu C, Sun Y, et al. Activation of Hif1α by the prolylhydroxylase inhibitor dimethyoxalyglycine decreases radiosensitivity. PLoS One. 2011;6(10):e26064
   PubMed Web of Science ®Google Scholar
• Forristal CE, Winkler IG, Nowlan B, et al. Pharmacologic stabilization of HIF-1α increases hematopoietic stem cell quiescence in vivo and accelerates blood recovery after severe irradiation. Blood. 2013;121(5):759–769.
   PubMed Web of Science ®Google Scholar
• Grimes CA, Jope RS. The multifaceted roles of glycogen synthase kinase 3beta in cellular signaling. Prog Neurobiol. 2001;65(4):391–426.
   PubMed Web of Science ®Google Scholar
• Thotala DK, Hallahan DE, Yazlovitskaya EM. Inhibition of glycogen synthase kinase 3 beta attenuates neurocognitive dysfunction resulting from cranial irradiation. Cancer Res. 2008;68(14):5859–5868.
   PubMed Web of Science ®Google Scholar
• Thotala DK, Geng L, Dickey AK, et al. A new class of molecular targeted radioprotectors: GSK-3beta inhibitors. Int J Radiat Oncol Biol Phys. 2010;76(2):557–565.
   PubMed Web of Science ®Google Scholar
• Thotala DK, Hallahan DE, Yazlovitskaya EM. Glycogen synthase kinase 3β inhibitors protect hippocampal neurons from radiation-induced apoptosis by regulating MDM2-p53 pathway. Cell Death Differ. 2012;19(3):387–396.
   PubMed Web of Science ®Google Scholar
• Barton KL, Misuraca K, Cordero F, et al. PD-0332991, a CDK4/6 inhibitor, significantly prolongs survival in a genetically engineered mouse model of brainstem glioma. PLoS One. 2013;8(10):e77639
   PubMed Web of Science ®Google Scholar
• Bartek J, Lukas J. Chk1 and Chk2 kinases in checkpoint control and cancer. Cancer Cell. 2003;3(5):421–429.
   PubMed Web of Science ®Google Scholar
• Chen L, Gilkes DM, Pan Y, et al. ATM and Chk2-dependent phosphorylation of MDMX contribute to p53 activation after DNA damage. Embo J. 2005;24(19):3411–3422.
   PubMed Web of Science ®Google Scholar
• Komarova EA, Chernov MV, Franks R, et al. Transgenic mice with p53-responsive lacZ: p53 activity varies dramatically during normal development and determines radiation and drug sensitivity in vivo. Embo J. 1997;16(6):1391–1400.
   PubMed Web of Science ®Google Scholar
• Komarov PG, Komarova EA, Kondratov RV, et al. A chemical inhibitor of p53 that protects mice from the side effects of cancer therapy. Science. 1999;285(5434):1733–1737.
   PubMed Web of Science ®Google Scholar
• Strom E, Sathe S, Komarov PG, et al. Skaliter R and others. Small-molecule inhibitor of p53 binding to mitochondria protects mice from gamma radiation. Nat Chem Biol. 2006;2(9):474–479.
   PubMed Web of Science ®Google Scholar
• Takai H, Naka K, Okada Y, et al. Chk2-deficient mice exhibit radioresistance and defective p53-mediated transcription. Embo J. 2002;21(19):5195–5205.
   PubMed Web of Science ®Google Scholar
• Carlessi L, Buscemi G, Larson G, et al. Biochemical and cellular characterization of VRX0466617, a novel and selective inhibitor for the checkpoint kinase Chk2. Mol Cancer Ther. 2007;6(3):935–944.
   PubMed Web of Science ®Google Scholar
• Jobson AG, Lountos GT, Lorenzi PL, et al. Cellular inhibition of checkpoint kinase 2 (Chk2) and potentiation of camptothecins and radiation by the novel Chk2 inhibitor PV1019 [7-nitro-1H-indole-2-carboxylic acid {4-[1-(guanidinohydrazone)-ethyl]-phenyl}-amide]. J Pharmacol Exp Ther. 2009;331(3):816–826.
   PubMed Web of Science ®Google Scholar
• Wander SA, Hennessy BT, Slingerland JM. Next-generation mTOR inhibitors in clinical oncology: how pathway complexity informs therapeutic strategy. J Clin Invest. 2011;121(4):1231–1241.
   PubMed Web of Science ®Google Scholar
• Chen C, Liu Y, Liu R, et al. TSC-mTOR maintains quiescence and function of hematopoietic stem cells by repressing mitochondrial biogenesis and reactive oxygen species. J Exp Med. 2008;205(10):2397–2408.
   PubMed Web of Science ®Google Scholar
• Castilho RM, Squarize CH, Chodosh LA, et al. mTOR mediates Wnt-induced epidermal stem cell exhaustion and aging. Cell Stem Cell. 2009;5(3):279–289.
   PubMed Web of Science ®Google Scholar
• Iglesias-Bartolome R, Patel V, Cotrim A, et al. mTOR inhibition prevents epithelial stem cell senescence and protects from radiation-induced mucositis. Cell Stem Cell. 2012;11(3):401–414.
   PubMed Web of Science ®Google Scholar
• Isenberg JS, Ridnour LA, Dimitry J, et al. CD47 is necessary for inhibition of nitric oxide-stimulated vascular cell responses by thrombospondin-1. J Biol Chem. 2006;281(36):26069–26080.
   PubMed Web of Science ®Google Scholar
• Isenberg JS, Ridnour LA, Perruccio EM, et al. Thrombospondin-1 inhibits endothelial cell responses to nitric oxide in a cGMP-dependent manner. Proc Natl Acad Sci USA. 2005;102(37):13141–13146.
   PubMed Web of Science ®Google Scholar
• Isenberg JS, Maxhimer JB, Hyodo F, et al. Thrombospondin-1 and CD47 limit cell and tissue survival of radiation injury. Am J Pathol. 2008;173(4):1100–1112.
   PubMed Web of Science ®Google Scholar
• Isenberg JS, Hyodo F, Pappan LK, et al. Blocking thrombospondin-1/CD47 signaling alleviates deleterious effects of aging on tissue responses to ischemia. Arterioscler Thromb Vasc Biol. 2007;27(12):2582–2588.
   PubMed Web of Science ®Google Scholar
• Liebmann J, DeLuca AM, Coffin D, et al. In vivo radiation protection by nitric oxide modulation. Cancer Res. 1994;54(13):3365–3368.
   PubMed Web of Science ®Google Scholar
• Maxhimer JB, Soto-Pantoja DR, Ridnour LA, et al. Radioprotection in normal tissue and delayed tumor growth by blockade of CD47 signaling. Sci Transl Med. 2009;1(3):3ra7
   PubMed Web of Science ®Google Scholar
• Soto-Pantoja DR, Miller TW, Pendrak ML, et al. CD47 deficiency confers cell and tissue radioprotection by activation of autophagy. Autophagy. 2012;8(11):1628–1642.
   PubMed Web of Science ®Google Scholar
• Friedman EJ. Immune modulation by ionizing radiation and its implications for cancer immunotherapy. Curr Pharm Des. 2002;8(19):1765–1780.
   PubMed Web of Science ®Google Scholar
• Haimovitz-Friedman A, Kan CC, Ehleiter D, et al. Ionizing radiation acts on cellular membranes to generate ceramide and initiate apoptosis. J Exp Med. 1994;180(2):525–535.
   PubMed Web of Science ®Google Scholar
• Mullen TD, Jenkins RW, Clarke CJ, et al. Ceramide synthase-dependent ceramide generation and programmed cell death: involvement of salvage pathway in regulating postmitochondrial events. J Biol Chem. 2011;286(18):15929–15942.
   PubMed Web of Science ®Google Scholar
• Alphonse G, Maalouf M, Battiston-Montagne P, et al. p53-independent early and late apoptosis is mediated by ceramide after exposure of tumor cells to photon or carbon ion irradiation. BMC Cancer. 2013;13:151
   PubMed Web of Science ®Google Scholar
• Santana P, Peña LA, Haimovitz-Friedman A, et al. Acid sphingomyelinase-deficient human lymphoblasts and mice are defective in radiation-induced apoptosis. Cell. 1996;86(2):189–199.
   PubMed Web of Science ®Google Scholar
• Hwang D, Popat R, Bragdon C, et al. Effects of ceramide inhibition on experimental radiation-induced oral mucositis. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2005;100(3):321–329.
   PubMed Web of Science ®Google Scholar
• Rotolo J, Stancevic B, Zhang J, et al. Anti-ceramide antibody prevents the radiation gastrointestinal syndrome in mice. J Clin Invest. 2012;122(5):1786–1790.
   PubMed Web of Science ®Google Scholar
• Bonnaud S, Niaudet C, Pottier G, et al. Sphingosine-1-phosphate protects proliferating endothelial cells from ceramide-induced apoptosis but not from DNA damage-induced mitotic death. Cancer Res. 2007;67(4):1803–1811.
   PubMed Web of Science ®Google Scholar
• Kagan VE, Borisenko GG, Tyurina YY, et al. Oxidative lipidomics of apoptosis: redox catalytic interactions of cytochrome c with cardiolipin and phosphatidylserine. Free Radic Biol Med. 2004;37(12):1963–1985.
   PubMed Web of Science ®Google Scholar
• Atkinson J, Kapralov AA, Yanamala N, et al. Samhan-Arias AK and others. A mitochondria-targeted inhibitor of cytochrome c peroxidase mitigates radiation-induced death. Nat Commun. 2011;2:497
   PubMed Web of Science ®Google Scholar
• Gottlieb TM, Oren M. p53 in growth control and neoplasia. Biochim Biophys Acta. 1996;1287(2-3):77–102.
   PubMed Web of Science ®Google Scholar
• Hendry JH, Cai WB, Roberts SA, et al. p53 deficiency sensitizes clonogenic cells to irradiation in the large but not the small intestine. Radiat Res. 1997;148(3):254–259.
   PubMed Web of Science ®Google Scholar
• Hasegawa M, Zhang Y, Niibe H, et al. Resistance of differentiating spermatogonia to radiation-induced apoptosis and loss in p53-deficient mice. Radiat Res. 1998;149(3):263–270.
   PubMed Web of Science ®Google Scholar
• Tron VA, Trotter MJ, Tang L, et al. p53-regulated apoptosis is differentiation dependent in ultraviolet B-irradiated mouse keratinocytes. Am J Pathol. 1998;153(2):579–585.
   PubMed Web of Science ®Google Scholar
• Westphal CH, Rowan S, Schmaltz C, et al. atm and p53 cooperate in apoptosis and suppression of tumorigenesis, but not in resistance to acute radiation toxicity. Nat Genet. 1997;16(4):397–401.
   PubMed Web of Science ®Google Scholar
• Sinn B, Schulze J, Schroeder G, et al. Pifithrin-α as a potential cytoprotective agent in radiotherapy: protection of normal tissue without decreasing therapeutic efficacy in glioma cells. Radiat Res. 2010;174(5):601–610.
   PubMed Web of Science ®Google Scholar
• Sohn D, Graupner V, Neise D, et al. Pifithrin-alpha protects against DNA damage-induced apoptosis downstream of mitochondria independent of p53. Cell Death Differ. 2009;16(6):869–878.
   PubMed Web of Science ®Google Scholar
• Marchenko ND, Zaika A, Moll UM. Death signal-induced localization of p53 protein to mitochondria. A potential role in apoptotic signaling. J Biol Chem. 2000;275(21):16202–16212.
   PubMed Web of Science ®Google Scholar
• Mustata G, Li M, Zevola N, et al. Development of small-molecule PUMA inhibitors for mitigating radiation-induced cell death. Curr Top Med Chem. 2011;11(3):281–290.
   PubMed Web of Science ®Google Scholar
• Qiu W, Carson-Walter EB, Liu H, et al. PUMA regulates intestinal progenitor cell radiosensitivity and gastrointestinal syndrome. Cell Stem Cell. 2008;2(6):576–583.
   PubMed Web of Science ®Google Scholar
• Shao L, Sun Y, Zhang Z, et al. Deletion of proapoptotic Puma selectively protects hematopoietic stem and progenitor cells against high-dose radiation. Blood. 2010;115(23):4707–4714.
   PubMed Web of Science ®Google Scholar
• Yu H, Shen H, Yuan Y, et al. Deletion of Puma protects hematopoietic stem cells and confers long-term survival in response to high-dose gamma-irradiation. Blood. 2010;115(17):3472–3480.
   PubMed Web of Science ®Google Scholar
• Leibowitz BJ, Qiu W, Liu H, et al. Uncoupling p53 functions in radiation-induced intestinal damage via PUMA and p21. Mol Cancer Res. 2011;9(5):616–625.
   PubMed Web of Science ®Google Scholar
• Kol R, Ben-Hur E. Radiation protection of stimulated human lymphocytes by nicotinamide. Radiat Environ Biophys. 1983;22(2):133–140.
   PubMed Web of Science ®Google Scholar
• Szeinfeld D. The multifactorial role of ATP in repair processes and radioprotection. Med Hypotheses. 1990;32(3):225–229.
   PubMed Web of Science ®Google Scholar
• Makedonov GP, Chekova VV, Yakubovskaya EL, et al. Modification of DNA repair by human interferons. Acta Biol Hung. 1990;41(1-3):187–197.
   PubMed Web of Science ®Google Scholar
• Hennig UG, Wang Q, Gee NH, et al. Protection and repair of gamma-radiation-induced lesions in mice with DNA or deoxyribonucleoside treatments. Mutat Res. 1996;350(1):247–254.
   PubMed Web of Science ®Google Scholar
• Dittmann KH, Gueven N, Mayer C, et al. The presence of wild-type TP53 is necessary for the radioprotective effect of the Bowman-Birk proteinase inhibitor in normal fibroblasts. Radiat Res. 1998;150(6):648–655.
   PubMed Web of Science ®Google Scholar
• Dittmann K, Virsik-Köpp P, Mayer C, et al. Bowman-Birk protease inhibitor activates DNA-dependent protein kinase and reduces formation of radiation-induced dicentric chromosomes. Int J Radiat Biol. 2003;79(10):801–808.
   PubMed Web of Science ®Google Scholar
• Fan S, Ma YX, Wang JA, et al. The cytokine hepatocyte growth factor/scatter factor inhibits apoptosis and enhances DNA repair by a common mechanism involving signaling through phosphatidyl inositol 3' kinase. Oncogene. 2000;19(18):2212–2223.
   PubMed Web of Science ®Google Scholar
• Panse JP, Storb R, Storer B, et al. Prolonged allogeneic marrow engraftment following nonmyeloablative conditioning using 100 cGy total body irradiation and pentostatin before and pharmacological immunosuppression after transplantation. Transplantation. 2005;80(10):1518–1521.
   PubMed Web of Science ®Google Scholar
• Kim K, Pollard JM, Norris AJ, et al. High-throughput screening identifies two classes of antibiotics as radioprotectors: tetracyclines and fluoroquinolones. Clin Cancer Res. 2009;15(23):7238–7245.
   PubMed Web of Science ®Google Scholar
• Epperly MW, Franicola D, Shields D, et al. Screening of antimicrobial agents for in vitro radiation protection and mitigation capacity, including those used in supportive care regimens for bone marrow transplant recipients. In Vivo. 2010;24(1):9–19.
   PubMed Web of Science ®Google Scholar
• Furuta Y, Hunter N, Barkley T, et al. Increase in radioresponse of murine tumors by treatment with indomethacin. Cancer Res. 1988;48(11):3008–3013.
   PubMed Web of Science ®Google Scholar
• Nishiguchi I, Furuta Y, Hunter N, et al. Radioprotection of hematopoietic tissues in mice by indomethacin. Radiat Res. 1990;122(2):188–192.
   PubMed Web of Science ®Google Scholar
• Hofer M, Pospísil M, Pipalová I, et al. Modulation of haemopoietic radiation response of mice by diclofenac in fractionated treatment. Physiol Res. 1996;45(3):213–220.
   PubMed Web of Science ®Google Scholar
• Hofer M, Pospísil M, Pipalová I. Radioprotective properties of flurbiprofen. Folia Biol (Praha). 1996;42(5):267–269.
   PubMed Web of Science ®Google Scholar
• Hofer M, Pospísil M, Znojil V, et al. Meloxicam, a cyclooxygenase 2 inhibitor, supports hematopoietic recovery in gamma-irradiated mice. Radiat Res. 2006;166(3):556–560.
   PubMed Web of Science ®Google Scholar
• Hofer M, Pospíšil M, Dušek L, et al. A single dose of an inhibitor of cyclooxygenase 2, meloxicam, administered shortly after irradiation increases survival of lethally irradiated mice. Radiat Res. 2011;176(2):269–272.
   PubMed Web of Science ®Google Scholar
• Zhou Q, Liao JK. Pleiotropic effects of statins. Basic research and clinical perspectives. Circ J. 2010;74(5):818–826.
   PubMed Web of Science ®Google Scholar
• Fritz G. Targeting the mevalonate pathway for improved anticancer therapy. Curr Cancer Drug Targets. 2009;9(5):626–638.
   PubMed Web of Science ®Google Scholar
• Nübel T, Damrot J, Roos WP, et al. Lovastatin protects human endothelial cells from killing by ionizing radiation without impairing induction and repair of DNA double-strand breaks. Clin Cancer Res. 2006;12(3 Pt 1):933–939.
   PubMed Web of Science ®Google Scholar
• Ostrau C, Hülsenbeck J, Herzog M, et al. Lovastatin attenuates ionizing radiation-induced normal tissue damage in vivo. Radiother Oncol. 2009;92(3):492–499.
   PubMed Web of Science ®Google Scholar
• Wang J, Boerma M, Fu Q, et al. Simvastatin ameliorates radiation enteropathy development after localized, fractionated irradiation by a protein C-independent mechanism. Int J Radiat Oncol Biol Phys. 2007;68(5):1483–1490.
   PubMed Web of Science ®Google Scholar
• Mahmoudi M, Gorenne I, Mercer J, et al. Statins use a novel Nijmegen breakage syndrome-1-dependent pathway to accelerate DNA repair in vascular smooth muscle cells. Circ Res. 2008;103(7):717–725.
   PubMed Web of Science ®Google Scholar
• Checker R, Pal D, Patwardhan RS, et al. Modulation of Caspase-3 activity using a redox active vitamin K3 analogue, plumbagin, as a novel strategy for radioprotection. Free Radic Biol Med. 2019;143:560–572.
   Google Scholar
• Talwar S, House R, Sundaramurthy S, et al. Inhibition of caspases protects mice from radiation-induced oral mucositis and abolishes the cleavage of RNA-binding protein HuR. J Biol Chem. 2014;289(6):3487–3500.
   PubMed Web of Science ®Google Scholar
• Anscher MS, Thrasher B, Rabbani Z, et al. Antitransforming growth factor-beta antibody 1D11 ameliorates normal tissue damage caused by high-dose radiation. Int J Radiat Oncol Biol Phys. 2006;65(3):876–881.
   PubMed Web of Science ®Google Scholar
• Xavier S, Piek E, Fujii M, et al. Amelioration of radiation-induced fibrosis: inhibition of transforming growth factor-beta signaling by halofuginone. J Biol Chem. 2004;279(15):15167–15176.
   PubMed Web of Science ®Google Scholar
• Anscher MS, Thrasher B, Zgonjanin L, et al. Small molecular inhibitor of transforming growth factor-beta protects against development of radiation-induced lung injury. Int J Radiat Oncol Biol Phys. 2008;71(3):829–837.
   PubMed Web of Science ®Google Scholar
• Floersheim GL. Calcium antagonists protect mice against lethal doses of ionizing radiation. Br J Radiol. 1992;65(779):1025–1029.
   PubMed Web of Science ®Google Scholar
• Nunia V, Sancheti G, Goyal PK. Protection of Swiss albino mice against whole-body gamma irradiation by diltiazem. BJR. 2007;80(950):77–84.
   Google Scholar
• Peng R, Zhang W, Zuo Z, et al. Dimethyl sulfoxide, a potent oral radioprotective agent, confers radioprotection of hematopoietic stem and progenitor cells independent of apoptosis. Free Radic Biol Med. 2020;153:1–11.
   PubMed Web of Science ®Google Scholar
• Sémont A, François S, Mouiseddine M, et al. Mesenchymal stem cells increase self-renewal of small intestinal epithelium and accelerate structural recovery after radiation injury. Adv Exp Med Biol. 2006;585:19–30.
   PubMed Web of Science ®Google Scholar
• Prockop DJ, Gregory CA, Spees JL. One strategy for cell and gene therapy: harnessing the power of adult stem cells to repair tissues. Proc Natl Acad Sci USA. 2003;100(Suppl 1):11917–11923.
   PubMed Web of Science ®Google Scholar
• Mouiseddine M, François S, Semont A, et al. Human mesenchymal stem cells home specifically to radiation-injured tissues in a non-obese diabetes/severe combined immunodeficiency mouse model. Br J Radiol. 2007;80(Spec No 1):S49–S55.
   PubMed Web of Science ®Google Scholar
• Hu KX, Sun QY, Guo M, et al. The radiation protection and therapy effects of mesenchymal stem cells in mice with acute radiation injury. Br J Radiol. 2010;83(985):52–58.
   PubMed Web of Science ®Google Scholar
• Sémont A, Mouiseddine M, François A, et al. Mesenchymal stem cells improve small intestinal integrity through regulation of endogenous epithelial cell homeostasis. Cell Death Differ. 2010;17(6):952–961.
   PubMed Web of Science ®Google Scholar
• Lange C, Brunswig-Spickenheier B, Cappallo-Obermann H, et al. Radiation rescue: mesenchymal stromal cells protect from lethal irradiation. PLoS One. 2011;6(1):e14486
   PubMed Web of Science ®Google Scholar
• Saha S, Bhanja P, Kabarriti R, et al. Bone marrow stromal cell transplantation mitigates radiation-induced gastrointestinal syndrome in mice. PLoS One. 2011;6(9):e24072.
   PubMed Web of Science ®Google Scholar
• Liu Y, Chen XH, Si YJ, et al. Reconstruction of hematopoietic inductive microenvironment after transplantation of VCAM-1-modified human umbilical cord blood stromal cells. PLoS One. 2012;7(2):e31741
   PubMed Web of Science ®Google Scholar
• Yang X, Balakrishnan I, Torok-Storb B, et al. Marrow stromal cell infusion rescues hematopoiesis in lethally irradiated mice despite rapid clearance after infusion. Adv Hematol. 2012;2012:142530
   PubMedGoogle Scholar
• Nagayama H, Misawa K, Tanaka H, et al. Transient hematopoietic stem cell rescue using umbilical cord blood for a lethally irradiated nuclear accident victim. Bone Marrow Transplant. 2002;29(3):197–204.
   PubMed Web of Science ®Google Scholar
• Azzam EI, Yang Z, Li M, et al. The effect of human cord blood therapy on the intestinal tract of lethally irradiated mice: possible use for mass casualties. Int J Radiat Biol. 2010;86(6):467–475.
   PubMed Web of Science ®Google Scholar
• Shim S, Lee SB, Lee JG, et al. Mitigating effects of hUCB-MSCs on the hematopoietic syndrome resulting from total body irradiation. Exp Hematol. 2013;41(4):346–353.e2.
   PubMed Web of Science ®Google Scholar
• Singh VK, Christensen J, Fatanmi OO, et al. Myeloid progenitors: a radiation countermeasure that is effective when initiated days after irradiation. Radiat Res. 2012;177(6):781–791.
   PubMed Web of Science ®Google Scholar
• Davies JE, Walker JT, Keating A. Concise review: Wharton's Jelly: the rich, but enigmatic, source of mesenchymal stromal cells. Stem Cells Transl Med. 2017;6(7):1620–1630.
   PubMed Web of Science ®Google Scholar
• Bandekar M, Maurya DK, Sharma D, et al. Xenogeneic transplantation of human WJ-MSCs rescues mice from acute radiation syndrome via Nrf-2-dependent regeneration of damaged tissues. Am J Transplant. 2020;20(8):2044–2057.
   PubMed Web of Science ®Google Scholar
• Singh VK, Seed TM. Pharmacological management of ionizing radiation injuries: current and prospective agents and targeted organ systems. Expert Opin Pharmacother. 2020;21(3):317–337.
   PubMed Web of Science ®Google Scholar
• Bhanja P, Saha S, Kabarriti R, et al. Protective role of R-spondin1, an intestinal stem cell growth factor, against radiation-induced gastrointestinal syndrome in mice. PLoS One. 2009;4(11):e8014.
   PubMed Web of Science ®Google Scholar
• Singh VK, Brown DS, Kao TC. Tocopherol succinate: a promising radiation countermeasure. Int Immunopharmacol. 2009;9(12):1423–1430.
   PubMed Web of Science ®Google Scholar
• Vadhan-Raj S, Goldberg JD, Perales MA, Berger DP, et al. Clinical applications of palifermin: amelioration of oral mucositis and other potential indications. J Cell Mol Med. 2013;17(11):1371–1384.
   PubMed Web of Science ®Google Scholar
• Weiss JF, Landauer MR. Protection against ionizing radiation by antioxidant nutrients and phytochemicals. Toxicology. 2003;189(1-2):1–20.
   PubMed Web of Science ®Google Scholar
• Prockop DJ. Further proof for an unpopular concept: a single cell from bone marrow can serve as a stem cell for both hematopoiesis and osteogenesis. Mol Ther. 2013;21(6):1116–1117.
   PubMed Web of Science ®Google Scholar