{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T06:34:27Z","timestamp":1793428467046,"version":"4.5.0"},"reference-count":26,"publisher":"Radiation Research Society","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Radiation Research"],"published-print":{"date-parts":[[2023,1,23]]},"abstract":"<jats:p>Acute exposure to high dose radiation can cause acute radiation syndrome (ARS), a potentially life-threatening illness. Individuals that survive ARS are at risk of developing the delayed effects of acute radiation exposure, with the lungs being particularly susceptible (DEARE-lung). For individuals at risk of radiation exposure, there are no Food and Drug Administration-approved medical countermeasures (MCMs) for prophylactic or post-exposure use that can prevent or mitigate DEARE-lung. BIO 300 is a novel formulation of synthetic genistein that has been extensively studied as a prophylactic MCM for the hematopoietic subsyndrome of ARS (H-ARS). Here, we used a C57L\/J mouse model of total-body irradiation (TBI) to investigate whether prophylactic administration of BIO 300 is able to prevent animals from developing DEARE-lung. Oral and parenteral formulations of BIO 300 administered prior to TBI were compared against standard of care, PEGfilgrastim, administered shortly after radiation exposure, and the combination of oral BIO 300 administered prior to TBI and with PEGfilgrastim administered post-exposure. All animals were exposed to 7.75 Gy cobalt-60 gamma-radiation and the primary endpoint was lung histopathology at 180 days post-TBI. Animals treated with BIO 300 had a significant reduction in the incidence of interstitial lung inflammation compared to vehicle groups for both the oral (0% vs. 47%) and parenteral (13% vs. 44%) routes of administration. Similar results were obtained for the incidence and severity of pulmonary fibrosis in animals treated with oral BIO 300 (incidence, 47% vs. 100% and mean severity score, 0.53 vs. 1.3) and parenteral BIO 300 (incidence, 63% vs. 100% and mean severity score, 0.69 vs. 1.7). PEGfilgrastim alone had no significant effect in reducing the incidence of inflammation or fibrosis compared to vehicle. The combination of oral BIO 300 and PEGfilgrastim significantly reduced the incidence of interstitial inflammation (13% vs. 46%) and the severity of pulmonary fibrosis (mean severity score, 0.93 vs. 1.6). Results in the C57L\/J mice were compared to those in CD2F1 mice, which are less prone to lung injury following total-body irradiation. Taken together, these studies indicate that BIO 300 is a promising MCM that is able to prophylactically protect against DEARE-lung.<\/jats:p>","DOI":"10.1667\/rade-22-00142.1","type":"journal-article","created":{"date-parts":[[2023,1,23]],"date-time":"2023-01-23T14:48:55Z","timestamp":1674485335000},"page":"294-300","source":"Crossref","is-referenced-by-count":17,"title":["The Radioprotectant, BIO 300, Protects the Lungs from Total-Body Irradiation Injury in C57L\/J Mice"],"prefix":"10.1667","volume":"199","author":[{"given":"Vijay K.","family":"Singh","sequence":"first","affiliation":[{"name":"Division of Radioprotectants, Department of Pharmacology and Molecular Therapeutics, F. Edward H\u00e9bert School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Artur A.","family":"Serebrenik","sequence":"additional","affiliation":[{"name":"Humanetics Corporation, Minneapolis, Minnesota"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oluseyi O.","family":"Fatanmi","sequence":"additional","affiliation":[{"name":"Division of Radioprotectants, Department of Pharmacology and Molecular Therapeutics, F. Edward H\u00e9bert School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen Y.","family":"Wise","sequence":"additional","affiliation":[{"name":"Division of Radioprotectants, Department of Pharmacology and Molecular Therapeutics, F. Edward H\u00e9bert School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alana D.","family":"Carpenter","sequence":"additional","affiliation":[{"name":"Division of Radioprotectants, Department of Pharmacology and Molecular Therapeutics, F. Edward H\u00e9bert School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brianna L.","family":"Janocha","sequence":"additional","affiliation":[{"name":"Division of Radioprotectants, Department of Pharmacology and Molecular Therapeutics, F. Edward H\u00e9bert School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael D.","family":"Kaytor","sequence":"additional","affiliation":[{"name":"Humanetics Corporation, Minneapolis, Minnesota"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1243","reference":[{"key":"1","unstructured":"EJ Hall  and AJ Giaccia  \"Radiobiology for the radiobiologist.\"  (2012)"},{"key":"17","unstructured":"\"Guide for the care and use of laboratory animals.\"  (2011)"},{"key":"18","doi-asserted-by":"crossref","unstructured":"IL Jackson, P Xu, C Hadley, et al.  \"Health Phys.\"  103, \"A preclinical rodent model of radiation-induced lung injury for medical countermeasure screening in accordance with the FDA animal rule.\" 463 (2012)","DOI":"10.1097\/HP.0b013e31826386ef"},{"key":"12","doi-asserted-by":"crossref","unstructured":"IL Jackson, PT Xu, G Nguyen, et al.  \"Health Phys.\"  106, \"Characterization of the dose response relationship for lung injury following acute radiation exposure in three well-established murine strains: Developing an interspecies bridge to link animal models with human lung.\" 48 (2014)","DOI":"10.1097\/HP.0b013e3182a32ccf"},{"key":"15","doi-asserted-by":"crossref","unstructured":"CJ Fryer, PJ Fitzpatrick, WD Rider, et al.  \"Int J Radiat Oncol Biol Phys.\"  4, \"Radiation pneumonitis: experience following a large single dose of radiation.\" 931 (1978)","DOI":"10.1016\/0360-3016(78)90002-0"},{"key":"14","doi-asserted-by":"crossref","unstructured":"J Van Dyk, TJ Keane, S Kan, et al.  \"Int J Radiat Oncol Biol Phys.\"  7, \"Radiation pneumonitis following large single dose irradiation: a re-evaluation based on absolute dose to lung.\" 461 (1981)","DOI":"10.1016\/0360-3016(81)90131-0"},{"key":"8","doi-asserted-by":"crossref","unstructured":"AK Cheema, Y Li, J Singh, et al.  \"Anim Microbiome.\"  3, \"Microbiome study in irradiated mice treated with BIO 300, a promising radiation countermeasure.\" 71 (2021)","DOI":"10.1186\/s42523-021-00132-1"},{"key":"2","doi-asserted-by":"crossref","unstructured":"NH Ding, JJ Li, LQ Sun,  \"Curr Drug Targets.\"  14, \"Molecular mechanisms and treatment of radiation-induced lung fibrosis.\" 1347 (2013)","DOI":"10.2174\/13894501113149990198"},{"key":"7","doi-asserted-by":"crossref","unstructured":"CT Ha, XH Li, D Fu, et al.  \"Radiat Res.\"  180, \"Genistein nanoparticles protect mouse hematopoietic system and prevent proinflammatory factors after gamma irradiation.\" 316 (2013)","DOI":"10.1667\/RR3326.1"},{"key":"9","doi-asserted-by":"crossref","unstructured":"MR Landauer, AJ Harvey, MD Kaytor, et al.  \"J Radiat Res.\"  60, \"Mechanism and therapeutic window of a genistein nanosuspension to protect against hematopoietic-acute radiation syndrome.\" 308 (2019)","DOI":"10.1093\/jrr\/rrz014"},{"key":"16","doi-asserted-by":"crossref","unstructured":"VK Singh, OO Fatanmi, SY Wise, et al.  \"Int J Radiat Biol.\"  98, \"A novel oral formulation of BIO 300 confers prophylactic radioprotection from acute radiation syndrome in mice.\" 958 (2022)","DOI":"10.1080\/09553002.2021.1981556"},{"key":"20","doi-asserted-by":"crossref","unstructured":"J Besplug, P Burke, A Ponton, et al.  \"Int J Radiat Biol.\"  81, \"Sex and tissue-specific differences in low-dose radiation-induced oncogenic signaling.\" 157 (2005)","DOI":"10.1080\/09553000500103512"},{"key":"22","doi-asserted-by":"crossref","unstructured":"M Babey, Y Wang, T Kubota, et al.  \"J Bone Miner Res.\"  30, \"Gender-Specific Differences in the Skeletal Response to Continuous PTH in Mice Lacking the IGF1 Receptor in Mature Osteoblasts.\" 1064 (2015)","DOI":"10.1002\/jbmr.2433"},{"key":"23","doi-asserted-by":"crossref","unstructured":"AM Patterson, S Vemula, PA Plett, et al.  \"Radiat Res.\"  198, \"Age and sex divergence in hematopoietic radiosensitivity in aged mouse models of the hematopoietic acute radiation syndrome.\" 221 (2022)","DOI":"10.1667\/RADE-22-00071.1"},{"key":"24","unstructured":"M Warner, B Huang, JA Gustafsson,  \"Trends Pharmacol Sci.\"  \"Estrogen Receptor beta as a Pharmaceutical Target.\" (2016)"},{"key":"25","doi-asserted-by":"crossref","unstructured":"MM Satyamitra, DR Cassatt, L Marzella,  \"Radiat Res.\"  197, \"A trans-agency workshop on the pathophysiology of radiation-induced lung injury.\" 408 (2022)","DOI":"10.1667\/RADE-21-00153.1"},{"key":"26","doi-asserted-by":"crossref","unstructured":"IL Jackson, Z Vujaskovic, JD Down,  \"Radiat Res.\"  173, \"Revisiting strain-related differences in radiation sensitivity of the mouse lung: recognizing and avoiding the confounding effects of pleural effusions.\" 10 (2010)","DOI":"10.1667\/RR1911.1"},{"key":"21","doi-asserted-by":"crossref","unstructured":"D Mukherjee, PJ Coates, SA Lorimore, et al.  \"J Pathol.\"  232, \"Responses to ionizing radiation mediated by inflammatory mechanisms.\" 289 (2014)","DOI":"10.1002\/path.4299"},{"key":"13","doi-asserted-by":"crossref","unstructured":"M Garofalo, A Bennett, AM Farese, et al.  \"Health Phys.\"  106, \"The delayed pulmonary syndrome following acute high-dose irradiation: a rhesus macaque model.\" 56 (2014)","DOI":"10.1097\/HP.0b013e3182a32b3f"},{"key":"6","doi-asserted-by":"crossref","unstructured":"TJ MacVittie, A Gibbs, AM Farese, et al.  \"Radiat Res.\"  187, \"AEOL 10150 mitigates radiation-induced lung injury in the nonhuman primate: Morbidity and mortality are administration schedule-dependent.\" 298 (2017)","DOI":"10.1667\/RR4413.1"},{"key":"19","doi-asserted-by":"crossref","unstructured":"IL Jackson, Z Vujaskovic, JD Down,  \"Radiat Res.\"  175, \"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.\" 510 (2011)","DOI":"10.1667\/RR2421.1"},{"key":"4","doi-asserted-by":"crossref","unstructured":"M Medhora, F Gao, T Gasperetti, et al.  \"Health Phys.\"  116, \"Delayed effects of acute radiation exposure (Deare) in juvenile and old rats: Mitigation by lisinopril.\" 529 (2019)","DOI":"10.1097\/HP.0000000000000920"},{"key":"10","doi-asserted-by":"crossref","unstructured":"IL Jackson, A Zodda, G Gurung, et al.  \"Br J Pharmacol.\"  174, \"BIO 300, a nanosuspension of genistein, mitigates pneumonitis\/fibrosis following high-dose radiation exposure in the C57L\/J murine model.\" 4738 (2017)","DOI":"10.1111\/bph.14056"},{"key":"5","doi-asserted-by":"crossref","unstructured":"C Rabender, E Mezzaroma, AG Mauro, et al.  \"Radiat Res.\"  186, \"IPW-5371 proves effective as a radiation countermeasure by mitigating radiation-induced late effects.\" 478 (2016)","DOI":"10.1667\/RR14403.2"},{"key":"11","doi-asserted-by":"crossref","unstructured":"VK Singh  and TM Seed  \"Expert Opin Investig Drugs.\"  29, \"BIO 300: a promising radiation countermeasure under advanced development for acute radiation syndrome and the delayed effects of acute radiation exposure.\" 429 (2020)","DOI":"10.1080\/13543784.2020.1757648"},{"key":"3","doi-asserted-by":"crossref","unstructured":"VK Singh  and TM Seed  \"Int J Radiat Biol.\"  97, \"Radiation countermeasures for hematopoietic acute radiation syndrome: growth factors, cytokines and beyond.\" 1526 (2021)","DOI":"10.1080\/09553002.2021.1969054"}],"container-title":["Radiation Research"],"original-title":[],"link":[{"URL":"https:\/\/meridian.allenpress.com\/radiation-research\/article-pdf\/doi\/10.1667\/RADE-22-00142.1\/3182734\/10.1667_rade-22-00142.1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/meridian.allenpress.com\/radiation-research\/article-pdf\/doi\/10.1667\/RADE-22-00142.1\/3182734\/10.1667_rade-22-00142.1.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T06:20:16Z","timestamp":1793427616000},"score":1,"resource":{"primary":{"URL":"https:\/\/bioone.org\/journals\/radiation-research\/volume-199\/issue-3\/RADE-22-00142.1\/The-Radioprotectant-BIO-300-Protects-the-Lungs-from-Total-Body\/10.1667\/RADE-22-00142.1.full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,1,23]]},"references-count":26,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2023,3,1]]}},"URL":"https:\/\/doi.org\/10.1667\/rade-22-00142.1","relation":{},"ISSN":["0033-7587","1938-5404"],"issn-type":[{"value":"0033-7587","type":"print"},{"value":"1938-5404","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,1,23]]}}}