{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T05:32:31Z","timestamp":1793424751023,"version":"4.5.0"},"reference-count":52,"publisher":"Radiation Research Society","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Radiation Research"],"published-print":{"date-parts":[[2023,11,28]]},"abstract":"<jats:p>The goal of this study was to establish a model of partial-body irradiation (PBI) sparing 2.5% of the bone marrow (BM2.5-PBI) that accurately recapitulates radiological\/nuclear exposure scenarios. Here we have reported a model which produces gastrointestinal (GI) damage utilizing a clinical linear accelerator (LINAC) with precise dosimetry, which can be used to develop medical countermeasures (MCM) for GI acute radiation syndrome (ARS) under the FDA animal rule. The PBI model (1 hind leg spared) was developed in male and female C57BL\/6 mice that received radiation doses ranging from 12\u201317 Gy with no supportive care. GI pathophysiology was assessed by crypt cell loss and correlated with peak lethality between days 4 and 10 after PBI. The radiation dose resulting in 50% mortality in 30 days (LD50\/30) was determined by probit analysis. Differential blood cell counts in peripheral blood, colony forming units (CFU) in bone marrow, and sternal megakaryocytes were analyzed between days 1\u201330, to assess the extent of hematopoietic ARS (H-ARS) injury. Radiation-induced GI damage was also assessed by measuring: 1. bacterial load (16S rRNA) by RT-PCR on days 4 and 7 after PBI in liver, spleen and jejunum, 2. liposaccharide binding protein (LBP) levels in liver, and 3. fluorescein isothiocyanate (FITC)-dextran, E-selectin, sP-selectin, VEGF, FGF-2, MMP-9, citrulline, and serum amyloid A (SAA) levels in serum. The LD50\/30 of male mice was 14.3 Gy (95% confidence interval 14.1\u201314.7 Gy) and of female mice was 14.5 Gy (95% confidence interval 14.3\u201314.7 Gy). Secondary endpoints included loss of viable crypts, higher bacterial loads in spleen and liver, higher LBP in liver, increased FITC-dextran and SAA levels, and decreased levels of citrulline and endothelial biomarkers in serum. The BM2.5-PBI model, developed for the first time with precise dosimetry, showed acute radiation-induced GI damage that is correlated with lethality, as well as a response to various markers of inflammation and vascular damage. Sex-specific differences were observed with respect to radiation dose response. Currently, no MCM is available as a mitigator for GI-ARS. This BM2.5-PBI mouse model can be regarded as the first high-throughput PBI model with precise dosimetry for developing MCMs for GI-ARS under the FDA animal rule.<\/jats:p>","DOI":"10.1667\/rade-23-00068.1","type":"journal-article","created":{"date-parts":[[2023,11,28]],"date-time":"2023-11-28T04:48:40Z","timestamp":1701146920000},"page":"19-34","source":"Crossref","is-referenced-by-count":14,"title":["Development of a Multi-Organ Radiation Injury Model with Precise Dosimetry with Focus on GI-ARS"],"prefix":"10.1667","volume":"201","author":[{"given":"Vidya P.","family":"Kumar","sequence":"first","affiliation":[{"name":"Armed Forces Radiobiology Research Institute, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20889"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kefale","family":"Wuddie","sequence":"additional","affiliation":[{"name":"Armed Forces Radiobiology Research Institute, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20889"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alena","family":"Tsioplaya","sequence":"additional","affiliation":[{"name":"Armed Forces Radiobiology Research Institute, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20889"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alia","family":"Weaver","sequence":"additional","affiliation":[{"name":"Armed Forces Radiobiology Research Institute, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20889"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory P.","family":"Holmes-Hampton","sequence":"additional","affiliation":[{"name":"Armed Forces Radiobiology Research Institute, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20889"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanchita P.","family":"Ghosh","sequence":"additional","affiliation":[{"name":"Armed Forces Radiobiology Research Institute, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20889"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1243","reference":[{"key":"18","doi-asserted-by":"crossref","unstructured":"AM Farese, AW Bennett, AM Gibbs, et al.  \"Health Phys.\"  116, \"Efficacy of Neulasta or Neupogen on H-ARS and GI-ARS Mortality and Hematopoietic Recovery in Nonhuman Primates After 10-Gy Irradiation With 2.5% Bone Marrow Sparing.\" (2019)","DOI":"10.1097\/HP.0000000000000878"},{"key":"49","doi-asserted-by":"crossref","unstructured":"S Garg, W Wang, BG Prabath, et al.  \"Radiat Res.\"  181, \"Bone marrow transplantation helps restore the intestinal mucosal barrier after total body irradiation in mice.\" 229 (2014)","DOI":"10.1667\/RR13548.1"},{"key":"52","doi-asserted-by":"crossref","unstructured":"AL DiCarlo, Z Perez Horta, CI Rios, et al.  \"Int J Radiat Biol.\"  97, \"Study logistics that can impact medical countermeasure efficacy testing in 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WF Blakely, DM Burmeister, et al.  \"Radiat Res.\"  196, \"Celebrating 60 Years of Accomplishments of the Armed Forces Radiobiology Research Institute1.\" 129 (2021)","DOI":"10.1667\/21-00064.1"},{"key":"29","unstructured":"\"Practice for use of an alanine-EPR dosimetry system.\""},{"key":"30","doi-asserted-by":"crossref","unstructured":"PR Almond, PJ Briggs, BM Coursey, et al.  \"Medical Phys.\"  26, \"AAPM's TG-51 protocol for clinical reference dosimetry of high-energy photon and electron beams.\" 1847 (1997)","DOI":"10.1118\/1.598691"},{"key":"31","doi-asserted-by":"crossref","unstructured":"JG Kiang, M Zhai, DL Bolduc, et al.  \"Radiat Res.\"  188, \"Combined Therapy of Pegylated G- CSF and Alxn4100TPO Improves Survival and Mitigates Acute Radiation Syndrome after Whole-Body Ionizing Irradiation Alone and Followed by Wound Trauma.\" 476 (2017)","DOI":"10.1667\/RR14647.1"},{"key":"33","doi-asserted-by":"crossref","unstructured":"I Brook, TJ MacVittie, RI Walker,  \"Infect Immun.\"  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(2013)","DOI":"10.1016\/j.jpedsurg.2013.03.030"},{"key":"38","doi-asserted-by":"crossref","unstructured":"P Chandrakesan, J Panneerselvam, R May, et al.  \"Mol Cancer Ther.\"  19, \"DCLK1-Isoform2 Alternative Splice Variant Promotes Pancreatic Tumor Immunosuppressive M2-Macrophage Polarization.\" 1539 (2020)","DOI":"10.1158\/1535-7163.MCT-19-0776"},{"key":"39","doi-asserted-by":"crossref","unstructured":"AR Crowe  and W Yue  \"Bio Protoc.\"  2, \"Updated: Semi-quantitative Determination of Protein Expression Using Immunohistochemistry Staining and Analysis.\" (2023)","DOI":"10.21769\/BioProtoc.4610"},{"key":"42","doi-asserted-by":"crossref","unstructured":"P Bhanja, S Saha, R Kabarriti, et al.  \"PLoS One.\"  4, \"Protective role of R- spondin1, an intestinal stem cell growth factor, against radiation-induced gastrointestinal syndrome in mice.\" e8014 (2009)","DOI":"10.1371\/journal.pone.0008014"},{"key":"43","doi-asserted-by":"crossref","unstructured":"Z Gao, Q Zhang, Y Han, et al.  \"Cytotherapy.\"  14, \"Mesenchymal stromal cell-conditioned medium prevents radiation-induced small intestine injury in mice.\" 267 (2012)","DOI":"10.3109\/14653249.2011.616194"},{"key":"44","unstructured":"\"Delayed Effects of Acute Radiation Exposure (DEARE) Models.\""},{"key":"46","doi-asserted-by":"crossref","unstructured":"BI Bell, J Vercellino, NP Brodin, et al.  \"Cancer Res.\"  82, \"Orthovoltage X-Rays Exhibit Increased Efficacy Compared with gamma-Rays in Preclinical Irradiation.\" 2678 (2022)","DOI":"10.1158\/0008-5472.CAN-22-0656"},{"key":"48","doi-asserted-by":"crossref","unstructured":"GP Holmes-Hampton, VP Kumar, K Valenzia, et al.  \"Cytogenet Genome Res.\"  \"Sex as a factor in murine radiation research: implications for countermeasure development.\" (2023)","DOI":"10.1159\/000531630"},{"key":"50","doi-asserted-by":"crossref","unstructured":"M Galotto, G Berisso, L Delfino, et al.  \"Experimental hematology.\"  27, \"Stromal damage as consequence of high-dose chemo\/radiotherapy in bone marrow transplant recipients.\" 1460 (1999)","DOI":"10.1016\/S0301-472X(99)00076-4"},{"key":"40","unstructured":"\"Fed Regist.\"  67, \"New drug and biological drug products; evidence needed to demonstrate effectiveness of new drugs when human efficacy studies are not ethical or feasible. 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