5,894
Views
107
CrossRef citations to date
0
Altmetric
Reviews

A review of radiation countermeasures focusing on injury-specific medicinals and regulatory approval status: part I. Radiation sub-syndromes, animal models and FDA-approved countermeasures

&
Pages 851-869 | Received 04 Jan 2017, Accepted 10 May 2017, Published online: 26 Jun 2017

References

  • Abdel-Mageed AS, Senagore AJ, Pietryga DW, Connors RH, Giambernardi TA, Hay RV, Deng W. 2009. Intravenous administration of mesenchymal stem cells genetically modified with extracellular superoxide dismutase improves survival in irradiated mice. Blood. 113:1201–1203.
  • Aebersold P. 2012. FDA experience with medical countermeasures under the Animal Rule. Adv Prev Med. 2012:507571.
  • Agay D, Scherthan H, Forcheron F, Grenier N, Herodin F, Meineke V, Drouet M. 2010. Multipotent mesenchymal stem cell grafting to treat cutaneous radiation syndrome: development of a new minipig model. Exp Hematol. 38:945–956.
  • Aleksandrova EN, Kalendo GS, Serebriakov NG. 1980. Radiation block of mitoses and the action of stimulating factors. Tsitologiia. 22:1453–1457.
  • Altas E, Ertekin MV, Kuduban O, Gundogdu C, Demirci E, Sutbeyaz Y. 2006. Effects of piracetam supplementation on cochlear damage occurring in guinea pigs exposed to irradiation. Biol Pharm Bull. 29:1460–1465.
  • Armed Forces Radiobiology Research Institute. 2013. Medical management of radiological casualities. Bethesda, MD: Armed Forces Radiobiology Research Institute.
  • Augustine AD, Gondre-Lewis T, McBride W, Miller L, Pellmar TC, Rockwell S. 2005. Animal models for radiation injury, protection and therapy. Radiat Res. 164:100–109.
  • Basile LA, Ellefson D, Gluzman-Poltorak Z, Junes-Gill K, Mar V, Mendonca S, Miller JD, Tom J, Trinh A, Gallaher TK. 2012. HemaMax™, a recombinant human interleukin-12, is a potent mitigator of acute radiation injury in mice and non-human primates. PLoS One. 7:e30434.
  • Benjamin GC, McGeary M, McCutchen SR. 2009. Assessing medical preparedness to respond to a terrorist nuclear event: workshop report. Washington, DC: The National Academies Press.
  • Benjamin SA, Lee AC, Angleton GM, Jaenke BS, Saunders WJ, Miller GK, Brewster RD. 1986. Life-span radiation effects studies in prenatally and postnatally exposed beagle dogs at Colorado State University. In: Thompson RC, Mahafffey JA, editors. Life span radiation effects studies in animals: what can they tell us? Springfield, VA: National Technical Information Service.
  • Benson KG, Paul-Murphy J, Hart AP, Keuler NS, Darien BJ. 2008. Coagulation values in normal ferrets (Mustela putorius furo) using selected methods and reagents. Vet Clin Pathol. 37:286–288.
  • Bergonie J, Tribondeau L. 1959. Interpretation of some results of radiotherapy and an attempt at determining a logical technique of treatment. Radiat Res. 11:587–588.
  • Bey E, Prat M, Duhamel P, Benderitter M, Brachet M, Trompier F, Battaglini P, Ernou I, Boutin L, Gourven M, et al. 2010. Emerging therapy for improving wound repair of severe radiation burns using local bone marrow-derived stem cell administrations. Wound Repair Regen. 18:50–58.
  • Bianchi E. 1963. Radioresistance induced by total-body grid irradiation in small doses and the behavior of guinea pigs after a subsequent lethal dose of X-ray. Minerva Radiol Fisioter Radiobiol. 14:500–506.
  • Bohuslavizki KH, Brenner W, Klutmann S, Hubner RH, Lassmann S, Feyerabend B, Luttges J, Tinnemeyer S, Clausen M, Henze E. 1998. Radioprotection of salivary glands by amifostine in high-dose radioiodine therapy. J Nucl Med. 39:1237–1242.
  • Bohuslavizki KH, Klutmann S, Jenicke L, Kroger S, Buchert R, Mester J, Clausen M. 1999. Salivary gland protection by S-2-(3-aminopropylamino)-ethylphosphorothioic acid (amifostine) in high-dose radioiodine treatment: results obtained in a rabbit animal model and in a double-blind multi-arm trial. Cancer Biother Radiopharm. 14:337–347.
  • Booth C, Tudor G, Tudor J, Katz BP, MacVittie TJ. 2012. Acute gastrointestinal syndrome in high-dose irradiated mice. Health Phys. 103:383–399.
  • Brennan PC, Carr KE, Seed T, McCullough JS. 1998. Acute and protracted radiation effects on small intestinal morphological parameters. Int J Radiat Biol. 73:691–698.
  • Brizel DM. 2007. Pharmacologic approaches to radiation protection. J Clin Oncol. 25:4084–4089.
  • Carnes BA, Grdina DJ. 1992. In vivo protection by the aminothiol WR-2721 against neutron-induced carcinogenesis. Int J Radiat Biol. 61:567–576.
  • Carpenter M, Epperly MW, Agarwal A, Nie S, Hricisak L, Niu Y, Greenberger JS. 2005. Inhalation delivery of manganese superoxide dismutase-plasmid/liposomes protects the murine lung from irradiation damage. Gene Ther. 12:685–693.
  • Carr KE. 2001. Effects of radiation damage on intestinal morphology. Int Rev Cytol. 208:1–119.
  • Carsten AL. 1984. Acute lethality: the hemopoietic syndrome in different species. In: Broerse JJ, MacVittie TJ, editors. Response of different species to total body irradiation. Dordrecht (The Netherlands): Martinus Niijhoff.
  • Carter AB, May MM, Perry WJ. 2007. The day after: action following a nuclear blast in a US city. Washington Quart. 30:19–32.
  • Cary LH, Ngudiankama BF, Salber RE, Ledney GD, Whitnall MH. 2012. Efficacy of radiation countermeasures depends on radiation quality. Radiat Res. 177:663–675.
  • Casarett GW. 1980. Radiation histopathology. Boca Raton, FL: CRC Press.
  • Centers for Disease Control and Prevention. 2016. Emergency Preparedness and Response [Online]. Available from: http://emergency.cdc.gov/radiation/countermeasures.asp
  • Ch’ang HJ, Maj JG, Paris F, Xing HR, Zhang J, Truman JP, Cardon-Cardo C, Haimovitz-Friedman A, Kolesnick R, Fuks Z. 2005. ATM regulates target switching to escalating doses of radiation in the intestines. Nat Med. 11:484–490.
  • Chen L, Brizel DM, Rabbani ZN, Samulski TV, Farrell CL, Larrier N, Anscher MS, Vujaskovic Z. 2004. The protective effect of recombinant human keratinocyte growth factor on radiation-induced pulmonary toxicity in rats. Int J Radiat Oncol Biol Phys. 60:1520–1529.
  • Chua HL, Plett PA, Sampson CH, Katz BP, Carnathan GW, MacVittie TJ, Lenden K, Orschell CM. 2014. Survival efficacy of the PEGylated G-CSFs, Maxy-G34, and Neulasta in a mouse model of lethal H-ARS, and residual bone marrow damage in treated survivors. Health Phys. 106:21–38.
  • Cohen EP, Bedi M, Irving AA, Jacobs E, Tomic R, Klein J, Lawton CA, Moulder JE. 2012. Mitigation of late renal and pulmonary injury after hematopoietic stem cell transplantation. Int J Radiat Oncol Biol Phys. 83:292–296.
  • Dagle GE, Sanders CL. 1984. Radionuclide injury to the lung. Environ Health Perspect. 55:129–137.
  • Dainiak N. 2002. Hematologic consequences of exposure to ionizing radiation. Exp Hematol. 30:513–528.
  • Dainiak N, Gent RN, Carr Z, Schneider R, Bader J, Buglova E, Chao N, Coleman CN, Ganser A, Gorin C, et al. 2011a. First global consensus for evidence-based management of the hematopoietic syndrome resulting from exposure to ionizing radiation. Disaster Med Pub Health Prep. 5:202–212.
  • Dainiak N, Gent RN, Carr Z, Schneider R, Bader J, Buglova E, Chao N, Coleman CN, Ganser A, Gorin C, et al. 2011b. Literature review and global consensus on management of acute radiation syndrome affecting nonhematopoietic organ systems. Disaster Med Pub Health Prep. 5:183–201.
  • Daly MJ. 2012. Death by protein damage in irradiated cells. DNA Repair (Amst). 11:12–21.
  • Danquechin Dorval E, Mueller GP, Eng RR, Durakovic A, Conklin JJ, Dubois A. 1985. Effect of ionizing radiation on gastric secretion and gastric motility in monkeys. Gastroenterology. 89:374–380.
  • Denham JW, Hauer-Jensen M, Peters LJ. 2001. Is it time for a new formalism to categorize normal tissue radiation injury? Int J Radiat Oncol Biol Phys. 50:1105–1106.
  • DiCarlo AL, Jackson IL, Shah JR, Czarniecki CW, Maidment BW, Williams JP. 2012. Development and licensure of medical countermeasures to treat lung damage resulting from a radiological or nuclear incident. Radiat Res. 177:717–721.
  • DiCarlo AL, Ramakrishnan N, Hatchett RJ. 2010. Radiation combined injury: overview of NIAID research. Health Phys. 98:863–867.
  • Ding NH, Li JJ, Sun LQ. 2013. Molecular mechanisms and treatment of radiation-induced lung fibrosis. Curr Drug Targets. 14:1347–1356.
  • Doctrow SR, Lopez A, Schock AM, Duncan NE, Jourdan MM, Olasz EB, Moulder JE, Fish BL, Mader M, Lazar J, et al. 2013. A synthetic superoxide dismutase/catalase mimetic EUK-207 mitigates radiation dermatitis and promotes wound healing in irradiated rat skin. J Invest Dermatol. 133:1088–1096.
  • Dorr H, Meineke V. 2011. Acute radiation syndrome caused by accidental radiation exposure – therapeutic principles. BMC Med. 9:126.
  • Drouet M, Mourcin F, Grenier N, Leroux V, Denis J, Mayol JF, Thullier P, Lataillade JJ, Herodin F. 2004. Single administration of stem cell factor, FLT-3 ligand, megakaryocyte growth and development factor, and interleukin-3 in combination soon after irradiation prevents nonhuman primates from myelosuppression: long-term follow-up of hematopoiesis. Blood. 103:878–885.
  • Dubois A, Jacobus JP, Grissom MP, Eng RR, Conklin JJ. 1984. Altered gastric emptying and prevention of radiation-induced vomiting in dogs. Gastroenterology. 86:444–448.
  • Dumont F, Le Roux A, Bischoff P. 2010. Radiation countermeasure agents: an update. Expert Opin Ther Pat. 20:73–101.
  • Elliott TB, Bolduc DL, Ledney GD, Kiang JG, Fatanmi OO, Wise SY, Romaine PL, Newman VL, Singh VK. 2015. Combined immunomodulator and antimicrobial therapy eliminates polymicrobial sepsis and modulates cytokine production in combined injured mice. Int J Radiat Biol. 91:690–702.
  • Elliott TB, Deutz NE, Gulani J, Koch A, Olsen CH, Christensen C, Chappell M, Whitnall MH, Moroni M. 2014. Gastrointestinal acute radiation syndrome in Göttingen minipigs (Sus scrofa domestica). Comp Med. 64:456–463.
  • Epperly MW, Carpenter M, Agarwal A, Mitra P, Nie S, Greenberger JS. 2004. Intraoral manganese superoxide dismutase-plasmid/liposome (MnSOD-PL) radioprotective gene therapy decreases ionizing irradiation-induced murine mucosal cell cycling and apoptosis. In Vivo. 18:401–410.
  • Farese AM, Casey DB, Smith WG, Vigneulle RM, McKearn JP, MacVittie TJ. 2001. Leridistim, a chimeric dual G-CSF and IL-3 receptor agonist, enhances multilineage hematopoietic recovery in a nonhuman primate model of radiation-induced myelosuppression: effect of schedule, dose, and route of administration. Stem Cells. 19:522–533.
  • Farese AM, Cohen MV, Katz BP, Smith CP, Gibbs A, Cohen DM, MacVittie TJ. 2013. Filgrastim improves survival in lethally irradiated nonhuman primates. Radiat Res. 179:89–100.
  • Farese AM, Cohen MV, Katz BP, Smith CP, Jackson W, 3rd, Cohen DM, MacVittie TJ. 2012a. A nonhuman primate model of the hematopoietic acute radiation syndrome plus medical management. Health Phys. 103:367–382.
  • Farese AM, Cohen MV, Stead RB, Jackson W 3rd, MacVittie TJ. 2012b. Pegfilgrastim administered in an abbreviated schedule, significantly improved neutrophil recovery after high-dose radiation-induced myelosuppression in rhesus macaques. Radiat Res. 178:403–413.
  • Farese AM, MacVittie TJ. 2015. Filgrastim for the treatment of hematopoietic acute radiation syndrome. Drugs Today. 51:537–548.
  • Fliedner TM, Dorr DH, Meineke V. 2005. Multi-organ involvement as a pathogenetic principle of the radiation syndromes: a study involving 110 case histories documented in SEARCH and classified as the bases of haematopoietic indicators of effect. BJR. (Suppl 27):1–8.
  • Forcheron F, Agay D, Scherthan H, Riccobono D, Herodin F, Meineke V, Drouet M. 2012. Autologous adipocyte derived stem cells favour healing in a minipig model of cutaneous radiation syndrome. PLoS One. 7:e31694.
  • Gao F, Fish BL, Szabo A, Doctrow SR, Kma L, Molthen RC, Moulder JE, Jacobs ER, Medhora M. 2012. Short-term treatment with a SOD/catalase mimetic, EUK-207, mitigates pneumonitis and fibrosis after single-dose total-body or whole-thoracic irradiation. Radiat Res. 178:468–480.
  • Gao F, Narayanan J, Joneikis C, Fish BL, Szabo A, Moulder JE, Molthen RC, Jacobs ER, Rao RN, Medhora M. 2013. Enalapril mitigates focal alveolar lesions, a histological marker of late pulmonary injury by radiation to the lung. Radiat Res. 179:465–474.
  • Garofalo M, Bennett A, Farese AM, Harper J, Ward A, Taylor-Howell C, Cui W, Gibbs A, Lasio G, Jackson W 3rd, et al. 2014a. The delayed pulmonary syndrome following acute high-dose irradiation: a rhesus macaque model. Health Phys. 106:56–72.
  • Garofalo MC, Ward AA, Farese AM, Bennett A, Taylor-Howell C, Cui W, Gibbs A, Prado KL, Macvittie TJ. 2014b. A pilot study in rhesus macaques to assess the treatment efficacy of a small molecular weight catalytic metalloporphyrin antioxidant (AEOL 10150) in mitigating radiation-induced lung damage. Health Phys. 106:73–83.
  • Geary RS, Swynnerton NF, Miller MA, Mangold DJ, Ludden T. 1989. Intraduodenal administration of ethiofos (WR-2721): dose proportionality study in the rhesus monkey. Res Commun Chem Pathol Pharmacol. 65:147–159.
  • Georges GE, Kuver RP, Jordan R, Aragon A, Yang Y, Lesnikova M, Lesnikov V, Sale GE, McDonald GB. 2012. Post-exposure oral 17,21-beclomethasone dipropionate (BDP) improves survival in a canine gastrointestinal acute radiation syndrome (GI-ARS) model. Poster presented at 58th Annual Meeting of the Radiation Research Society; San Juan, Puerto Rico.
  • Geraci JP, Jackson KL, Mariano MS. 1985. The intestinal radiation syndrome: sepsis and endotoxin. Radiat Res. 101:442–450.
  • Geraci JP, Sun MC, Mariano MS. 1995. Amelioration of radiation nephropathy in rats by postirradiation treatment with dexamethasone and/or captopril. Radiat Res. 143:58–68.
  • Ghosh SN, Zhang R, Fish BL, Semenenko VA, Li XA, Moulder JE, Jacobs ER, Medhora M. 2009. Renin-angiotensin system suppression mitigates experimental radiation pneumonitis. Int J Radiat Oncol Biol Phys. 75:1528–1536.
  • Gianni AM, Bregni M, Siena S, Villa S, Sciorelli GA, Ravagnani F, Pellegris G, Bonadonna G. 1989. Rapid and complete hemopoietic reconstitution following combined transplantation of autologous blood and bone marrow cells. A changing role for high dose chemo-radiotherapy? Hematol Oncol. 7:139–148.
  • Gluzman-Poltorak Z, Mendonca SR, Vainstein V, Kha H, Basile LA. 2014a. Randomized comparison of single dose of recombinant human IL-12 versus placebo for restoration of hematopoiesis and improved survival in rhesus monkeys exposed to lethal radiation. J Hematol Oncol. 7:31.
  • Gluzman-Poltorak Z, Vainstein V, Basile LA. 2014b. Recombinant interleukin-12, but not granulocyte-colony stimulating factor, improves survival in lethally irradiated nonhuman primates in the absence of supportive care: evidence for the development of a frontline radiation medical countermeasure. Am J Hematol. 89:868–873.
  • Goans RE, Holloway EC, Berger ME, Ricks RC. 1997. Early dose assessment following severe radiation accidents. Health Phys. 72:513–518.
  • Gokare P, Navaraj A, Zhang S, Motoyama N, Sung SS, Finnberg NK. 2016. Targeting of Chk2 as a countermeasure to dose-limiting toxicity triggered by topoisomerase-II (TOP2) poisons. Oncotarget. 7:29520–29530.
  • Gourmelon P, Benderitter M, Bertho JM, Huet C, Gorin NC, De Revel P. 2010. European consensus on the medical management of acute radiation syndrome and analysis of the radiation accidents in Belgium and Senegal. Health Phys. 98:825–832.
  • Gratwohl A, John L, Baldomero H, Roth J, Tichelli A, Nissen C, Lyman SD, Wodnar-Filipowicz A. 1998. FLT-3 ligand provides hematopoietic protection from total body irradiation in rabbits. Blood. 92:765–769.
  • Grdina DJ, Carnes BA, Grahn D, Sigdestad CP. 1991. Protection against late effects of radiation by S-2-(3-aminopropylamino)-ethylphosphorothioic acid. Cancer Res. 51:4125–4130.
  • Gulbahar O, Aricioglu A, Akmansu M, Turkozer Z. 2009. Effects of radiation on protein oxidation and lipid peroxidation in the brain tissue. Transplant Proc. 41:4394–4396.
  • Hahn FF, Muggenburg BA, Menache MG, Guilmette RA, Boecker BB. 1999. Comparative stochastic effects of inhaled alpha- and beta-particle-emitting radionuclides in beagle dogs. Radiat Res. 152:S19–S22.
  • Hakim SG, Kosmehl H, Lauer I, Nadrowitz R, Wedel T, Sieg P. 2005. A comparative study on the protection profile of lidocaine, amifostine, and pilocarpin on the parotid gland during radiotherapy. Cancer Res. 65:10486–10493.
  • Hall EJ, Giaccia AJ. 2012. Radiobiology for the radiobiologist. Philadelphia, PA: Lippincott Williams and Wilkins.
  • Hankey KG, Farese AM, Blaauw EC, Gibbs AM, Smith CP, Katz BP, Tong Y, Prado KL, MacVittie TJ. 2015. Pegfilgrastim improves survival of lethally irradiated nonhuman primates. Radiat Res. 183:643–655.
  • Haston CK, Zhou X, Gumbiner-Russo L, Irani R, Dejournett R, Gu X, Weil M, Amos CI, Travis EL. 2002. Universal and radiation-specific loci influence murine susceptibility to radiation-induced pulmonary fibrosis. Cancer Res. 62:3782–3788.
  • Herodin F, Mestries JC, Janodet D, Martin S, Mathieu J, Gascon MP, Pernin MO, Ythier A. 1992. Recombinant glycosylated human interleukin-6 accelerates peripheral blood platelet count recovery in radiation-induced bone marrow depression in baboons. Blood. 80:688–695.
  • Herodin F, Roy L, Grenier N, Delaunay C, Bauge S, Vaurijoux A, Gregoire E, Martin C, Alonso A, Mayol JF, et al. 2007. Antiapoptotic cytokines in combination with pegfilgrastim soon after irradiation mitigates myelosuppression in nonhuman primates exposed to high irradiation dose. Exp Hematol. 35:1172–1181.
  • Herrera JL, Vigneulle RM, Gage T, MacVittie TJ, Nold JB, Dubois A. 1995. Effect of radiation and radioprotection on small intestinal function in canines. Dig Dis Sci. 40:211–218.
  • Hilf R, Adachi R, Eckfeldt G. 1961. Effect of dietary supplementation with broccoli on X-irradiation-induced enzyme changes in the guinea pig. Radiat Res. 15:86–93.
  • Hill RP. 2005. Radiation effects on the respiratory system. BJR. (Suppl. 27):75–81.
  • Hoel DG, Carnes BA, Dedrick RL, Fry RJM, Grahn D, Griffith WC, Groer PG, Preston RJ, Clifton KH, Miller SC, Shuller HM, Seed TM. 2005. Extrapolation of radiation-induced cancer risks from nonhuman experimental systems to humans. Bethesda, MD: National Council of Radiation Protection.
  • Holler V, Buard V, Gaugler MH, Guipaud O, Baudelin C, Sache A, Perez Mdel R, Squiban C, Tamarat R, Milliat F, et al. 2009. Pravastatin limits radiation-induced vascular dysfunction in the skin. J Invest Dermatol. 129:1280–1291.
  • Hopewell JW, Rezvani M, Moustafa HF. 2000. The pig as a model for the study of radiation effects on the lung. Int J Radiat Biol. 76:447–452.
  • Hosoi Y, Kurishita A, Ono T, Sakamoto K. 1992. Effect of recombinant human granulocyte colony-stimulating factor on survival in lethally irradiated mice. Acta Oncol. 31:59–63.
  • Inoue T, Hirabayashi Y, Mitsui H, Sasaki H, Cronkite EP, Bullis JE Jr, Bond VP, Yoshida K. 1995. Survival of spleen colony-forming units (CFU-S) of irradiated bone marrow cells in mice: evidence for the existence of a radioresistant subfraction. Exp Hematol. 23:1296–1300.
  • International Atomic Energy Agency. 2000. The radiological accident in Istanbul [Online]. Available from: http://www-pub.iaea.org/books/IAEABooks/6071/The-Radiological-Accident-in-Istanbul
  • Jackson IL, Vujaskovic Z, Down JD. 2010. Revisiting strain-related differences in radiation sensitivity of the mouse lung: recognizing and avoiding the confounding effects of pleural effusions. Radiat Res. 173:10–20.
  • Jackson IL, Vujaskovic Z, Down JD. 2011. A further comparison of pathologies after thoracic irradiation among different mouse strains: finding the best preclinical model for evaluating therapies directed against radiation-induced lung damage. Radiat Res. 175:510–518.
  • Jackson IL, Xu P, Hadley C, Katz BP, McGurk R, Down JD, Vujaskovic Z. 2012. A preclinical rodent model of radiation-induced lung injury for medical countermeasure screening in accordance with the FDA animal rule. Health Phys. 103:463–473.
  • Jacquet P, Vankerkom J, Lambiet-Collier M. 1994. The female guinea pig, a useful model for the genetic hazard of radiation in man; preliminary results on germ cell radiosensitivity in foetal, neonatal and adult animals. Int J Radiat Biol. 65:357–367.
  • Jahraus CD, Schemera B, Rynders P, Ramos M, Powell C, Faircloth J, Brawner WR. 2010. Rifaximin diminishes neutropenia following potentially lethal whole-body radiation. Exp Biol Med (Maywood). 235:900–905.
  • Jenrow KA, Brown SL, Liu J, Kolozsvary A, Lapanowski K, Kim JH. 2010. Ramipril mitigates radiation-induced impairment of neurogenesis in the rat dentate gyrus. Radiat Oncol. 5:6.
  • Jiao W, Kiang JG, Cary L, Elliott TB, Pellmar TC, Ledney GD. 2009. COX-2 inhibitors are contraindicated for treatment of combined injury. Radiat Res. 172:686–697.
  • Jourdan MM, Lopez A, Olasz EB, Duncan NE, Demara M, Kittipongdaja W, Fish BL, Mader M, Schock A, Morrow NV, et al. 2011. Laminin 332 deposition is diminished in irradiated skin in an animal model of combined radiation and wound skin injury. Radiat Res. 176:636–648.
  • Jurkovic V, Vokrouhlicky L. 1963. Cardiovascular changes during radiation disease. Sb Ved Pr Lek Fak Karlovy Univerzity Hradci Kralove. 6:5–10.
  • Kam WW, Banati RB. 2013. Effects of ionizing radiation on mitochondria. Free Radic Biol Med. 65:607–619.
  • Kataoka Y, Basic I, Perrin J, Grdina DJ. 1992. Antimutagenic effects of radioprotector WR-2721 against fission-spectrum neurons and 60Co gamma-rays in mice. Int J Radiat Biol. 61:387–392.
  • Kiang JG, Garrison BR, Burns TM, Zhai M, Dews IC, Ney PH, Cary LH, Fukumoto R, Elliott TB, Ledney GD. 2012. Wound trauma alters ionizing radiation dose assessment. Cell Biosci. 2:20.
  • Kiang JG, Jiao W, Cary LH, Mog SR, Elliott TB, Pellmar TC, Ledney GD. 2010. Wound trauma increases radiation-induced mortality by activation of iNOS pathway and elevation of cytokine concentrations and bacterial infection. Radiat Res. 173:319–332.
  • Kiang JG, Smith JT, Anderson MN, Swift JM, Christensen CL, Gupta P, Balakathiresan N, Maheshwari RK. 2015. Hemorrhage exacerbates radiation effects on survival, leukocytopenia, thrombopenia, erythropenia, bone marrow cell depletion and hematopoiesis, and inflammation-associated microRNAs expression in kidney. PLoS One. 10:e0139271.
  • Kiang JG, Zhai M, Liao PJ, Bolduc DL, Elliott TB, Gorbunov NV. 2014a. Pegylated G-CSF inhibits blood cell depletion, increases platelets, blocks splenomegaly, and improves survival after whole-body ionizing irradiation but not after irradiation combined with burn. Oxid Med Cell Longev. 2014:481392.
  • Kiang JG, Zhai M, Liao PJ, Elliott TB, Gorbunov NV. 2014b. Ghrelin therapy improves survival after whole-body ionizing irradiation or combined with burn or wound: amelioration of leukocytopenia, thrombocytopenia, splenomegaly, and bone marrow injury. Oxid Med Cell Longev. 2014:215858.
  • Kim JH, Jenrow KA, Brown SL. 2014. Mechanisms of radiation-induced normal tissue toxicity and implications for future clinical trials. Radiat Oncol J. 32:103–115.
  • Kim JH, Kolozsvary A, Jenrow KA, Brown SL. 2012. Plerixafor, a CXCR4 antagonist, mitigates skin radiation-induced injury in mice. Radiat Res. 178:202–206.
  • King GL. 1988. Characterization of radiation-induced emesis in the ferret. Radiat Res. 114:599–612.
  • King GL, Rabin BM, Weatherspoon JK. 1999. 5-HT3 receptor antagonists ameliorate emesis in the ferret evoked by neutron or proton radiation. Aviat Space Environ Med. 70:485–492.
  • Kma L, Gao F, Fish BL, Moulder JE, Jacobs ER, Medhora M. 2012. Angiotensin converting enzyme inhibitors mitigate collagen synthesis induced by a single dose of radiation to the whole thorax. J Radiat Res. 53:10–17.
  • Kobayashi T, Ohmori T, Yanai M, Kawanishi G, Mitsuyama M, Nomoto K. 1991. The analysis of the defense mechanism against indigenous bacterial translocation in X-irradiated mice. Microbiol Immunol. 35:315–324.
  • Kouvaris JR, Kouloulias VE, Vlahos LJ. 2007. Amifostine: the first selective-target and broad-spectrum radioprotector. Oncologist. 12:738–747.
  • Krigsfeld GS, Savage AR, Billings PC, Lin L, Kennedy AR. 2014a. Evidence for radiation-induced disseminated intravascular coagulation as a major cause of radiation-induced death in ferrets. Int J Radiat Oncol Biol Phys. 88:940–946.
  • Krigsfeld GS, Shah JB, Sanzari JK, Lin L, Kennedy AR. 2014b. Evidence of disseminated intravascular coagulation in a porcine model following radiation exposure. Life Sci Space Res (Amst). 3:1–9.
  • Krimsky M, Dagan A, Aptekar L, Ligumsky M, Yedgar S. 2000. Assessment of intestinal permeability in rats by permeation of inulin-fluorescein. J Basic Clin Physiol Pharmacol. 11:143–153.
  • Krivokrysenko VI, Shakhov AN, Singh VK, Bone F, Kononov Y, Shyshynova I, Cheney A, Maitra RK, Purmal A, Whitnall MH, et al. 2012. Identification of granulocyte colony-stimulating factor and interleukin-6 as candidate biomarkers of CBLB502 efficacy as a medical radiation countermeasure. J Pharmacol Exp Ther. 343:497–508.
  • Krivokrysenko VI, Toshkov IA, Gleiberman AS, Krasnov P, Shyshynova I, Bespalov I, Maitra RK, Narizhneva NV, Singh VK, Whitnall MH, et al. 2015. The Toll-like receptor 5 agonist Entolimod mitigates lethal acute radiation syndrome in non-human primates. PLoS One. 10:e0135388.
  • Lang IM, Sarna SK, Condon RE. 1986. Gastrointestinal motor correlates of vomiting in the dog: quantification and characterization as an independent phenomenon. Gastroenterology. 90:40–47.
  • Lataillade JJ, Doucet C, Bey E, Carsin H, Huet C, Clairand I, Bottollier-Depois JF, Chapel A, Ernou I, Gourven M, et al. 2007. New approach to radiation burn treatment by dosimetry-guided surgery combined with autologous mesenchymal stem cell therapy. Regen Med. 2:785–794.
  • Laterveer L, Zijlmans JM, Liehl E, Willemze R, Fibbe WE. 1996. Accelerated platelet reconstitution following transplantation of bone marrow cells derived from IL-6-treated donor mice. Ann Hematol. 73:239–245.
  • Lee JG, Park S, Bae CH, Jang WS, Lee SJ, Lee DN, Myung JK, Kim CH, Jin YW, Lee SS, et al. 2016. Development of a minipig model for lung injury induced by a single high-dose radiation exposure and evaluation with thoracic computed tomography. J Radiat Res. 57:201–209.
  • Lemaire G, Maas J. 1984. Haematopoietic syndrome in pigs. In: Broerse JJ, Macvittie TJ, editors. Response of different species to total body irradiation. Dordrecht, The Netherlands: Martinus Niijhoff.
  • Li M, Yu ZY, Xing S, Ou HL, Xiong GL, Xie L, Zhao YF, Han AR, Shan YJ, Liu XL, et al. 2011. High dose granulocyte colony-stimulating factor enhances survival and hematopoietic reconstruction in canines irradiated by 2.3 Gy mixed fission neutron and gamma ray. Zhongguo Shi Yan Xue Ye Xue Za Zhi. 19:991–998.
  • Lopez M, Martin M. 2011. Medical management of the acute radiation syndrome. Rep Pract Oncol Radiother. 16:138–146.
  • Lutgens LC, Blijlevens NM, Deutz NE, Donnelly JP, Lambin P, de Pauw BE. 2005. Monitoring myeloablative therapy-induced small bowel toxicity by serum citrulline concentration: a comparison with sugar permeability tests. Cancer. 103:191–199.
  • MacVittie TJ, Monroy RL, Farese AM, Seiler FR, Williams D. 1991. Cytokine therapy in canine and primate models of radiation-induced marrow aplasia. Behring Inst Mitt. 90:1–13.
  • MacVittie TJ, Farese AM, Patchen ML, Myers LA. 1994. 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. 84:2515–2522.
  • MacVittie TJ, Monroy RL, Patchen ML, Souza LM. 1990. Therapeutic use of recombinant human G-CSF (rhG-CSF) in a canine model of sublethal and lethal whole-body irradiation. Int J Radiat Biol. 57:723–736.
  • Mahmud N, Pang W, Cobbs C, Alur P, Borneman J, Dodds R, Archambault M, Devine S, Turian J, Bartholomew A, et al. 2004. Studies of the route of administration and role of conditioning with radiation on unrelated allogeneic mismatched mesenchymal stem cell engraftment in a nonhuman primate model. Exp Hematol. 32:494–501.
  • Makrauer FL, Oates E, Becker J, Abrams R, O’Connor T, McCallum R, Shumaker J. 1999. Does local irradiation affect gastric emptying in humans? Am J Med Sci. 317:33–37.
  • Mandel L, Travnicek J, Talafantova M, Zahradnickova M. 1980. The LD50/30 and the survival time in whole-body gamma-irradiated conventional and germfree Minnesota miniature piglets. Z Versuchstierkd. 22:96–100.
  • Marks LB, Yu X, Vujaskovic Z, Small W Jr, Folz R, Anscher MS. 2003. Radiation-induced lung injury. Semin Radiat Oncol. 13:333–345.
  • Martin C, Roman V, Agay D, Fatome M. 1998. Anti-emetic effect of ondansetron and granisetron after exposure to mixed neutron and gamma irradiation. Radiat Res. 149:631–636.
  • Mason KA, Withers HR, McBride WH, Davis CA, Smathers JB. 1989. Comparison of the gastrointestinal syndrome after total-body or total-abdominal irradiation. Radiat Res. 117:480–488.
  • Mavragani IV, Laskaratou DA, Frey B, Candeias SM, Gaipl US, Lumniczky K, Georgakilas AG. 2016. Key mechanisms involved in ionizing radiation-induced systemic effects. A current review. Toxicol Res. 5:12–33.
  • Mays CW, Taylor GN, Lloyd RD. 1986. Toxicity ratios: Their use and abuse in predicting the risk from induced cancer. In: Thompson RC, Mahaffey JA, editors. Life span radiation effects studies in animals: what can they tell us? Springfield, VA: NTIS; p. 299–310.
  • McCann DGC. 2006. Radiation poisoning: current concepts in the acute radiation syndrome. Am J Clin Med. 3:13–21.
  • McLaughlin RF Jr, Tyler WS, Canada RO. 1966. Subgross pulmonary anatomy of the rabbit, rat, and guinea pig, with additional notes on the human lung. Am Rev Respir Dis. 94:380–387.
  • Medhora M, Gao F, Fish BL, Jacobs ER, Moulder JE, Szabo A. 2012. Dose-modifying factor for captopril for mitigation of radiation injury to normal lung. J Radiat Res. 53:633–640.
  • Medhora M, Gao F, Wu Q, Molthen RC, Jacobs ER, Moulder JE, Fish BL. 2014. Model development and use of ACE inhibitors for preclinical mitigation of radiation-induced injury to multiple organs. Radiat Res. 182:545–555.
  • Moroni M, Coolbaugh TV, Lombardini E, Mitchell JM, Moccia KD, Shelton LJ, Nagy V, Whitnall MH. 2011a. Hematopoietic radiation syndrome in the Göttingen minipig. Radiat Res. 176:89–101.
  • Moroni M, Lombardini E, Salber R, Kazemzedeh M, Nagy V, Olsen C, Whitnall MH. 2011b. Hematological changes as prognostic indicators of survival: similarities between Göttingen minipigs, humans, and other large animal models. PLoS One. 6:e25210.
  • Moroni M, Ngudiankama BF, Christensen C, Olsen CH, Owens R, Lombardini ED, Holt RK, Whitnall MH. 2013. The Göttingen minipig is a model of the hematopoietic acute radiation syndrome: G-colony stimulating factor stimulates hematopoiesis and enhances survival from lethal total-body γ-irradiation. Int J Radiat Oncol Biol Phys. 86:986–992.
  • Moulder JE. 2014. 2013 Dade W. Moeller lecture: medical countermeasures against radiological terrorism. Health Phys. 107:164–171.
  • Moulder JE, Cohen EP. 2005. Radiation-induced multi-organ involvement and failure: the contribution of radiation effects on the renal system. BJR. (Suppl. 27):82–88.
  • Moulder JE, Robbins ME, Cohen EP, Hopewell JW, Ward WF. 1998. Pharmacologic modification of radiation-induced late normal tissue injury. Cancer Treat Res. 93:129–151.
  • Muggenburg BA, Hahn FF, Menache MG, Guilmette RA, Boecker BB. 1999. Comparative deterministic effects of inhaled, insoluble alpha- and beta-particle-emitting radionuclides in dogs. Radiat Res. 152:S23–S26.
  • Mujica-Mota MA, Salehi P, Devic S, Daniel SJ. 2014. Safety and otoprotection of metformin in radiation-induced sensorineural hearing loss in the guinea pig. Otolaryngol Head Neck Surg. 150:859–865.
  • Nash RA, Schuening FG, Seidel K, Appelbaum FR, Boone T, Deeg HJ, Graham TC, Hackman R, Sullivan-Pepe M, Storb R. 1994. Effect of recombinant canine granulocyte-macrophage colony-stimulating factor on hematopoietic recovery after otherwise lethal total body irradiation. Blood. 83:1963–1970.
  • National Institute of Allergic and Infectious Diseases. 2015. Pegfilgrastim approved for treating acute radiation syndrome [Online]. Available from: https://www.niaid.nih.gov/topics/radnuc/Pages/pegfilgrastim.aspx
  • Norol F, Drouet M, Mathieu J, Debili N, Jouault H, Grenier N, Laplanche A, Vainchenker W, Herodin F. 2000. Ex vivo expanded mobilized peripheral blood CD34+ cells accelerate haematological recovery in a baboon model of autologous transplantation. Br J Haematol. 109:162–172.
  • Nothdurft W, Kreja L, Selig C. 1997. Acceleration of hemopoietic recovery in dogs after extended-field partial-body irradiation by treatment with colony-stimulating factors: rhG-CSF and rhGM-CSF. Int J Radiat Oncol Biol Phys. 37:1145–1154.
  • Nothdurft W, Selig C, Fliedner TM, Hintz-Obertreis P, Kreja L, Krumwieh D, Kurrle R, Seiler FR, Weinsheimer W. 1992. Haematological effects of rhGM-CSF in dogs exposed to total-body irradiation with a dose of 2.4 Gy. Int J Radiat Biol. 61:519–531.
  • O’Connor MM, Mayberg MR. 2000. Effects of radiation on cerebral vasculature: a review. Neurosurgery. 46:138–149; discussion 150-131.
  • Okayasu R, Suetomi K, Yu Y, Silver A, Bedford JS, Cox R, Ullrich RL. 2000. A deficiency in DNA repair and DNA-PKcs expression in the radiosensitive BALB/c mouse. Cancer Res. 60:4342–4345.
  • Okunieff P, Xu J, Hu D, Liu W, Zhang L, Morrow G, Pentland A, Ryan JL, Ding I. 2006. Curcumin protects against radiation-induced acute and chronic cutaneous toxicity in mice and decreases mRNA expression of inflammatory and fibrogenic cytokines. Int J Radiat Oncol Biol Phys. 65:890–898.
  • Osmond DG, Roylance PJ, Lee WR, Ramsell TG, Yoffey JM. 1966. The effect of unilateral limb shielding on the haemopoietic response of the guinea-pig to gamma irradiation (150 r.). Br J Haematol. 12:365–375.
  • Otterson MF, Sarna SK, Leming SC, Moulder JE, Fink JG. 1992. Effects of fractionated doses of ionizing radiation on colonic motor activity. Am J Physiol. 263:G518–G526.
  • Otterson MF, Sarna SK, Moulder JE. 1988. Effects of fractionated doses of ionizing radiation on small intestinal motor activity. Gastroenterology. 95:1249–1257.
  • Patchen ML, MacVittie TJ. 1994. Granulocyte colony-stimulating factor and amifostine (Ethyol) synergize to enhance hemopoietic reconstitution and increase survival in irradiated animals. Semin Oncol. 21:26–32.
  • Peebles DD, Soref CM, Copp RR, Thunberg AL, Fahl WE. 2012. ROS-scavenger and radioprotective efficacy of the new PrC-210 aminothiol. Radiat Res. 178:57–68.
  • Pellmar TC, Rockwell S. 2005. Priority list of research areas for radiological nuclear threat countermeasures. Radiat Res. 163:115–123.
  • Peter RU, Braun-Falco O, Birioukov A, Hacker N, Kerscher M, Peterseim U, Ruzicka T, Konz B, Plewig G. 1994. Chronic cutaneous damage after accidental exposure to ionizing radiation: the Chernobyl experience. J Am Acad Dermatol. 30:719–723.
  • Peter RU, Gottlober P. 2002. Management of cutaneous radiation injuries: diagnostic and therapeutic principles of the cutaneous radiation syndrome. Mil Med. 167:110–112.
  • Peter RU, Gottlober P, Nadeshina N, Krahn G, Plewig G, Kind P. 1997. Radiation lentigo. A distinct cutaneous lesion after accidental radiation exposure. Arch Dermatol. 133:209–211.
  • Prise KM, Schettino G, Folkard M, Held KD. 2005. New insights on cell death from radiation exposure. Lancet Oncol. 6:520–528.
  • Reeves G. 2014. Overview of use of G-CSF and GM-CSF in the treatment of acute radiation injury. Health Phys. 106:699–703.
  • Rivina L, Davoren M, Schiestl RH. 2014. Radiation-induced myeloid leukemia in murine models. Hum Genomics. 8:13.
  • Robbins ME, Zhao W, Garcia-Espinosa MA, Diz DI. 2010. Renin-angiotensin system blockers and modulation of radiation-induced brain injury. Curr Drug Targets. 11:1413–1422.
  • Rosen EM, Day R, Singh VK. 2015. New approaches to radiation protection. Front Oncol. 4:381.
  • Rosenthal SA, Harber LC, Baer RL, Friedman M. 1960. Survival of guinea pigs after lethal irradiation and homologus bone marrow injections. Radiat Res. 13:496–501.
  • Ryan JL, Heckler CE, Ling M, Katz A, Williams JP, Pentland AP, Morrow GR. 2013. Curcumin for radiation dermatitis: a randomized, double-blind, placebo-controlled clinical trial of thirty breast cancer patients. Radiat Res. 180:34–43.
  • Saha S, Bhanja P, Kabarriti R, Liu L, Alfieri AA, Guha C. 2011. Bone marrow stromal cell transplantation mitigates radiation-induced gastrointestinal syndrome in mice. PLoS One. 6:e24072.
  • Sanzari JK, Krigsfeld GS, Shuman AL, Diener AK, Lin L, Mai W, Kennedy AR. 2015. Effects of a granulocyte colony stimulating factor, Neulasta, in mini pigs exposed to total body proton irradiation. Life Sci Space Res (Amst). 5:13–20.
  • Sanzari JK, Wan XS, Krigsfeld GS, King GL, Miller A, Mick R, Gridley DS, Wroe AJ, Rightnar S, Dolney D, et al. 2013. Effects of solar particle event proton radiation on parameters related to ferret emesis. Radiat Res. 180:166–176.
  • Satyamitra MM, DiCarlo AL, Taliaferro L. 2016. Understanding the pathophysiology and challenges of development of medical countermeasures for radiation-induced vascular/endothelial cell injuries: report of a NIAID workshop, August 20, 2015. Radiat Res. 186:99–111.
  • Schuening FG, Appelbaum FR, Deeg HJ, Sullivan-Pepe M, Graham TC, Hackman R, Zsebo KM, Storb R. 1993. Effects of recombinant canine stem cell factor, a c-kit ligand, and recombinant granulocyte colony-stimulating factor on hematopoietic recovery after otherwise lethal total body irradiation. Blood. 81:20–26.
  • Schuening FG, Storb R, Goehle S, Graham TC, Appelbaum FR, Hackman R, Souza LM. 1989. Effect of recombinant human granulocyte colony-stimulating factor on hematopoiesis of normal dogs and on hematopoietic recovery after otherwise lethal total body irradiation. Blood. 74:1308–1313.
  • Schultheiss TE, Kun LE, Ang KK, Stephens LC. 1995. Radiation response of the central nervous system. Int J Radiat Oncol Biol Phys. 31:1093–1112.
  • Seed TM. 2005. Radiation protectants: current status and future prospects. Health Phys. 89:531–545.
  • Seed TM, Fritz TE, Tolle DV, Poole CM, Lomard LS, Doyle DE, Kaspar LV. 1984. Survival patterns and hemopathological responses of dogs under continuous gamma irradiation. In: Broerse JJ, Macvittie TJ, editors. Response of different species to total body irradiation. Dordrecht, The Netherlands: Martinus Niijhoff.
  • Seed TM, Fry SA, Neta R, Weiss JF, Jarrett DG, Thomassen D. 2002a. Prevention and treatments: summary statement. Mil Med. 167:87–93.
  • Seed TM, Inal C, Dobson ME, Ghose S, Hilyard E, Tolle D, Fritz TE. 2002b. Accommodative responses to chronic irradiation: effects of dose, dose rate, and pharmacological response modifiers. Mil Med. 167:82–86.
  • Seed TM, Tolle DV, Fritz TE, 2002c. Haematological responses to chronic irradiation: The past Argonne experience and future AFRRI initiatives. In: Fliedner TM, Feinendegen LE, Hopewell JW, editors. Chronic irradiation: tolerance and failure in complex biological systems. Advanced research workshop on protracted, intermittent or chronic irradiation: biological effects and mechanisms of tolerance (2001: Ulm, Germany). London, UK: British Institute of Radiology.
  • Semont A, Francois S, Mouiseddine M, Francois A, Sache A, Frick J, Thierry D, Chapel A. 2006. Mesenchymal stem cells increase self-renewal of small intestinal epithelium and accelerate structural recovery after radiation injury. Adv Exp Med Biol. 585:19–30.
  • Sevan’kaev AV, Kozlov VM. 1974. Mitotic activity of human lymphocytes irradiated at different stages of the cell cycle. Radiobiologiia. 14:117–119.
  • Sharplin J, Franko AJ. 1989a. A quantitative histological study of strain-dependent differences in the effects of irradiation on mouse lung during the early phase. Radiat Res. 119:1–14.
  • Sharplin J, Franko AJ. 1989b. A quantitative histological study of strain-dependent differences in the effects of irradiation on mouse lung during the intermediate and late phases. Radiat Res. 119:15–31.
  • Shim S, Jang WS, Lee SJ, Jin S, Kim J, Lee SS, Bang HY, Jeon BS, Park S. 2014. Development of a new minipig model to study radiation-induced gastrointestinal syndrome and its application in clinical research. Radiat Res. 181:387–395.
  • Shin SC, Kang YM, Kim HS. 2010. Life span and thymic lymphoma incidence in high- and low-dose-rate irradiated AKR/J mice and commonly expressed genes. Radiat Res. 174:341–346.
  • Singh VK, Beattie LA, Seed TM. 2013. Vitamin E: tocopherols and tocotrienols as potential radiation countermeasures. J Radiat Res. 54:973–988.
  • Singh VK, Ducey EJ, Brown DS, Whitnall MH. 2012. A review of radiation countermeasure work ongoing at the Armed Forces Radiobiology Research Institute. Int J Radiat Biol. 88:296–310.
  • Singh VK, Kulkarni S, Fatanmi OO, Wise SY, Newman VL, Romaine PL, Hendrickson H, Gulani J, Ghosh SP, Kumar KS, et al. 2016a. Radioprotective efficacy of gamma-tocotrienol in nonhuman primates. Radiat Res. 185:285–298.
  • Singh VK, Newman VL, Romaine PL, Wise SY, Seed TM. 2014a. Radiation countermeasure agents: an update (2011–2014). Expert Opin Ther Pat. 24:1229–1255.
  • Singh VK, Newman VL, Seed TM. 2015a. Colony-stimulating factors for the treatment of the hematopoietic component of the acute radiation syndrome (H-ARS): a review. Cytokine. 71:22–37.
  • Singh VK, Romaine PL, Newman VL, Seed TM. 2016b. Medical countermeasures for unwanted CBRN exposures: part II radiological and nuclear threats with review of recent countermeasure patents. Expert Opin Ther Pat. 26:1399–1408.
  • Singh VK, Romaine PL, Seed TM. 2015b. Medical countermeasures for radiation exposure and related injuries: characterization of medicines, FDA-approval status and inclusion into the Strategic National Stockpile. Health Phys. 108:607–630.
  • Singh VK, Thrall KD, Hauer-Jensen M. 2016c. Minipigs as models in drug discovery. Expert Opin Drug Discov. 11:1131–1134.
  • Singh VK, Wise SY, Fatanmi OO, Beattie LA, Seed TM. 2014b. Preclinical development of a bridging therapy for radiation casualties: appropriate for high risk personnel. Health Phys. 106:689–698.
  • Singh VK, Wise SY, Fatanmi OO, Scott J, Romaine PL, Newman VL, Verma A, Elliott TB, Seed TM. 2014c. Progenitors mobilized by gamma-tocotrienol as an effective radiation countermeasure. PLoS One. 9:e114078.
  • Slauson DO, Hahn FF, Benjamin SA, Chiffelle TL, Jones RK. 1976. Inflammatory sequences in acute pulmonary radiation injury. Am J Pathol. 82:549–572.
  • Soligenix Inc. 2016. OrbeShield™ for gastrointestinal acute radiation syndrome (GI ARS) [Online]. Princeton, NJ: Soligenix Inc. Available from: http://www.soligenix.com/pipeline/vaccinesbiodefense/orbeshield-for-gastrointestinal-acute-radiation-syndrome-gi-ars/
  • Stickney DR, Dowding C, Authier S, Garsd A, Onizuka-Handa N, Reading C, Frincke JM. 2007. 5-androstenediol improves survival in clinically unsupported rhesus monkeys with radiation-induced myelosuppression. Int Immunopharmacol. 7:500–505.
  • Stickney DR, Dowding C, Garsd A, Ahlem C, Whitnall M, McKeon M, Reading C, Frincke J. 2006. 5-androstenediol stimulates multilineage hematopoiesis in rhesus monkeys with radiation-induced myelosuppression. Int Immunopharmacol. 6:1706–1713.
  • Stone HB, Moulder JE, Coleman CN, Ang KK, Anscher MS, Barcellos-Hoff MH, Dynan WS, Fike JR, Grdina DJ, Greenberger JS, et al. 2004. Models for evaluating agents intended for the prophylaxis, mitigation and treatment of radiation injuries. Report of an NCI Workshop, December 3–4, 2003. Radiat Res. 162:711–728.
  • Sureda A, Kadar E, Valls A, Garcia-Lopez J. 1998. Granulocyte colony-stimulating factor administered as a single intraperitoneal injection modifies the lethal dose95/30 in irradiated B6D2F1 mice. Haematologica. 83:863–864.
  • Swift JM, Smith JT, Kiang JG. 2015. Ciprofloxacin therapy results in mitigation of ATP loss after irradiation combined with wound trauma: preservation of pyruvate dehydrogenase and inhibition of pyruvate dehydrogenase kinase 1. Radiat Res. 183:684–692.
  • Tanikawa S, Nose M, Aoki Y, Tsuneoka K, Shikita M, Nara N. 1990. Effects of recombinant human granulocyte colony-stimulating factor on the hematologic recovery and survival of irradiated mice. Blood. 76:445–449.
  • Thompson RC. 1989. Life-span effects of ionizing radiation in the beagle dog [Online]. Pacific Northwest Laboratory, Battelle Memorial Institute. Available from: http://www.iaea.org/inis/collection/NCLCollectionStore/_Public/20/071/20071717.pdf
  • Travis EL. 2001. Organizational response of normal tissues to irradiation. Semin Radiat Oncol. 11:184–196.
  • Travis EL, Tucker SL. 1986. The relationship between functional assays of radiation response in the lung and target cell depletion. Br J Cancer Suppl. 7:304–319.
  • U.S. Food and Drug Administration. 2015a. FDA approves Neupogen for treatment of patients with radiation-induced myelosuppression following a radiological/nuclear incident [Online]. Silver Spring, MD: U.S. Food and Drug Administration. Available from: http://www.fda.gov/EmergencyPreparedness/Counterterrorism/MedicalCountermeasures/AboutMCMi/ucm443245.htm
  • U.S. Food and Drug Administration. 2015b. Guidance for industry: product development under the Animal Rule [Online]. Available from: http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM399217.pdf
  • Vasin MV, Semenov LF, Suvorov NN, Antipov VV, Ushakov IB, Ilyin LA, Lapin BA. 2014. Protective effect and the therapeutic index of indralin in juvenile rhesus monkeys. J Radiat Res. 55:1048–1055.
  • Vriesendorp HM, van Bekkum DW, 1984. Susceptibility to total body irradiation. In: Broerse JJ, Macvittie TJ, editors. Response of different species to total body irradiation. Dordrecht, The Netherlands: Martinus Niijhoff.
  • Vujaskovic Z, Batinic-Haberle I, Rabbani ZN, Feng QF, Kang SK, Spasojevic I, Samulski TV, Fridovich I, Dewhirst MW, Anscher MS. 2002. A small molecular weight catalytic metalloporphyrin antioxidant with superoxide dismutase (SOD) mimetic properties protects lungs from radiation-induced injury. Free Radic Biol Med. 33:857–863.
  • Vujaskovic Z, Marks LB, Anscher MS. 2000. The physical parameters and molecular events associated with radiation-induced lung toxicity. Semin Radiat Oncol. 10:296–307.
  • Wagemaker G, Neelis KJ, Hartong SCC, Wognum AW, Thomas GR, Fielder PJ, Eaton DL. 1998. The efficacy of recombinant TPO in murine and nonhuman primate models for myelosuppression and stem cell transplantation. Stem Cells. 16(Suppl. 2):127–141.
  • Wang Z, Yang WL, Jacob A, Aziz M, Wang P. 2015. Human ghrelin mitigates intestinal injury and mortality after whole body irradiation in rats. PLoS One. 10:e0118213.
  • Ward WF, Molteni A, Ts’ao CH. 1989. Radiation-induced endothelial dysfunction and fibrosis in rat lung: modification by the angiotensin converting enzyme inhibitor CL242817. Radiat Res. 117:342–350.
  • Warrington JP, Ashpole N, Csiszar A, Lee YW, Ungvari Z, Sonntag WE. 2013. Whole brain radiation-induced vascular cognitive impairment: mechanisms and implications. J Vasc Res. 50:445–457.
  • Waselenko JK, MacVittie TJ, Blakely WF, Pesik N, Wiley AL, Dickerson WE, Tsu H, Confer DL, Coleman CN, Seed T, et al. 2004. Medical management of the acute radiation syndrome: recommendations of the Strategic National Stockpile Radiation Working Group. Ann Intern Med. 140:1037–1051.
  • Weinstock DM, Case C Jr, Bader JL, Chao NJ, Coleman CN, Hatchett RJ, Weisdorf DJ, Confer DL. 2008. Radiologic and nuclear events: contingency planning for hematologists/oncologists. Blood. 111:5440–5445.
  • Weiss JF, Landauer MR. 2009. History and development of radiation-protective agents. Int J Radiat Biol. 85:539–573.
  • Williams JP, Brown SL, Georges GE, Hauer-Jensen M, Hill RP, Huser AK, Kirsch DG, Macvittie TJ, Mason KA, Medhora MM, et al. 2010. Animal models for medical countermeasures to radiation exposure. Radiat Res. 173:557–578.
  • Williams JP, Jackson IL, Shah JR, Czarniecki CW, Maidment BW, DiCarlo AL. 2012. Animal models and medical countermeasures development for radiation-induced lung damage: report from an NIAID Workshop. Radiat Res. 177:e0025–0039.
  • Wilson DA, Brigantic A, Morgan WF. 2011. The association of inbreeding with lung fibrosis incidence in Beagle dogs that inhaled 238PuO2 or 239PuO2. Radiat Res. 176:781–786.
  • Wisniewski K, Piekarska T, Danysz A. 1972. Reaction of the small intestine of guinea pigs to barium chloride in irradiation sickness. Acta Physiol Pol. 23:159–166.
  • Withers HR, Elkind MM. 1968. Dose-survival characteristics of epithelial cells of mouse intestinal mucosa. Radiology. 91:998–1000.
  • Yu ZY, Li M, Han AR, Xing S, Ou HL, Xiong GL, Xie L, Zhao YF, Xiao H, Shan YJ, et al. 2011. RhG-CSF improves radiation-induced myelosuppression and survival in the canine exposed to fission neutron irradiation. J Radiat Res. 52:472–480.
  • Zawaski JA, Yates CR, Miller DD, Kaffes CC, Sabek OM, Afshar SF, Young DA, Yang Y, Gaber MW. 2014. Radiation combined injury models to study the effects of interventions and wound biomechanics. Radiat Res. 182:640–652.
  • Zhang K, Tian Y, Yin L, Zhang M, Beck LA, Zhang B, Okunieff P, Zhang L, Vidyasagar S. 2011. Fibroblast growth factor-peptide improves barrier function and proliferation in human keratinocytes after radiation. Int J Radiat Oncol Biol Phys. 81:248–254.
  • Zhu X, Liu Y. 2009. Effects of intranasal corticosteroids on radiated nasal mucosa of guinea pig. Lin Chung Er Bi Yan Hou Tou Jing Wai Ke Za Zhi. 23:364–368.
  • Zoetelief J, Hennen LA, Broerse JJ. 1984. Some practical aspects of dosimetry and dose specification for whole body irradiation. In: Broerse JJ, Macvittie TJ, editors. Response of different species to total body irradiation. Netherlands: Springer.