{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T00:54:57Z","timestamp":1791248097436,"version":"4.1.0"},"reference-count":54,"publisher":"Radiation Research Society","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Radiation Research"],"published-print":{"date-parts":[[2024,7,22]]},"abstract":"<jats:p>After a large-scale radiological or nuclear event, hundreds of thousands of people may be exposed to ionizing radiation and require subsequent medical management. Acute exposure to moderate doses (2\u20136 Gy) of radiation can lead to the hematopoietic acute radiation syndrome, in which the bone marrow (BM) is severely compromised, and severe hemorrhage and infection are common. Previously, we have developed a panel of intracellular protein markers (FDXR, ACTN1, DDB2, BAX, p53 and TSPYL2), designed to reconstruct absorbed radiation dose from human peripheral blood (PB) leukocyte samples in humanized mice up to 3 days after exposure. The objective of this work was to continue to use the humanized mouse model to evaluate biomarker dose-\/ time- kinetics in human PB leukocytes in vivo, at an earlier (day 2) and later (day 7) time point, after exposure to total-body irradiation (TBI) doses of 0 to 2 Gy of X rays. In addition, to assess hematological sensitivity and radiation-induced injury, PB leukocyte cell counts, human BM hematopoietic stem cell (HSC) and progenitor cell [multipotent progenitor (MPP), common myeloid progenitor (CMP), granulocyte myeloid progenitor (GMP), megakaryocyte\/erythrocyte progenitor (MEP) and multi-lymphoid progenitor (MLP)] levels were measured, and their correlation was also examined as the BM damages are difficult to assess by routine tests. Peripheral blood B-cells were significantly lower after TBI doses of 0.5 Gy on day 2 and 2 Gy on days 2 and 7; T-cells were significantly reduced only on day 2 after 2 Gy TBI. Bone marrow HSCs and MPP cells showed a dose-dependent depletion after irradiation with 0.5 Gy and 2 Gy on day 2, and after 1 Gy and 2 Gy on day 7. Circulating B cells correlated with HSCs, MPP and MLP cells on day 2, whereas T cells correlated with MPP, and myeloid cells correlated with MLP cells. On day 7, B cells correlated with MPP, CMP, GMP and MEP, while myeloid cells correlated with CMP, GMP and MEP. The intracellular leukocyte biomarkers were able to discriminate unirradiated and irradiated samples at different time points calculated by receiver operating characteristic (ROC) curve. Using machine learning algorithm methods, combining ACTN1, p53, TSPYL2 and PBT cell and PB-B cell counts served as a strong predictor (area under the ROC &gt;0.8) to distinguish unirradiated and irradiated samples independent of the days after TBI. The results further validated our biomarker-based triage assay and additionally evaluated the radiation sensitivity of the hematopoietic system after TBI exposures.<\/jats:p>","DOI":"10.1667\/rade-24-00049.1","type":"journal-article","created":{"date-parts":[[2024,7,21]],"date-time":"2024-07-21T20:01:16Z","timestamp":1721592076000},"page":"541-551","source":"Crossref","is-referenced-by-count":3,"title":["Biomarkers for Radiation Biodosimetry and Correlation with Hematopoietic Injury in a Humanized Mouse Model"],"prefix":"10.1667","volume":"202","author":[{"given":"Qi","family":"Wang","sequence":"first","affiliation":[{"name":"Center for Radiological Research, Columbia University Irving Medical Center, New York, New York 10032"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bezalel A.","family":"Bacon","sequence":"additional","affiliation":[{"name":"Center for Radiological Research, Columbia University Irving Medical Center, New York, New York 10032"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Taveras","sequence":"additional","affiliation":[{"name":"Center for Radiological Research, Columbia University Irving Medical Center, New York, New York 10032"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle A.","family":"Phillippi","sequence":"additional","affiliation":[{"name":"Center for Radiological Research, Columbia University Irving Medical Center, New York, New York 10032"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuefeng","family":"Wu","sequence":"additional","affiliation":[{"name":"Center for Radiological Research, Columbia University Irving Medical Center, New York, New York 10032"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Constantinos G.","family":"Broustas","sequence":"additional","affiliation":[{"name":"Center for Radiological Research, Columbia University Irving Medical Center, New York, New York 10032"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Igor","family":"Shuryak","sequence":"additional","affiliation":[{"name":"Center for Radiological Research, Columbia University Irving Medical Center, New York, New York 10032"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helen C.","family":"Turner","sequence":"additional","affiliation":[{"name":"Center for Radiological Research, Columbia University Irving Medical Center, New York, New York 10032"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1243","reference":[{"key":"53","doi-asserted-by":"crossref","unstructured":"I Friesecke, K Beyrer, TM Fliedner,  \"Br J Radiol.\"  74, \"How to cope with radiation accidents: The medical management.\" 121 (2001)","DOI":"10.1259\/bjr.74.878.740121"},{"key":"28","doi-asserted-by":"crossref","unstructured":"Q Wang, MA Rodrigues, M Repin, et al.  \"Radiat Res.\"  191, \"automated triage radiation biodosimetry: integrating imaging flow cytometry with high-throughput robotics to perform the cytokinesis-block micronucleus assay.\" 342 (2019)","DOI":"10.1667\/RR15243.1"},{"key":"30","doi-asserted-by":"crossref","unstructured":"Y Lee, Q Wang, I Shuryak, et al.  \"Radiat Oncol.\"  14, \"Development of a high-throughput gamma-H2AX assay based on imaging flow cytometry.\" 150 (2019)","DOI":"10.1186\/s13014-019-1344-7"},{"key":"29","doi-asserted-by":"crossref","unstructured":"Q Wang, M Pujol-Canadell, M Taveras, et al.  \"Radiat Environ Biophys.\"  59, \"DNA damage response in peripheral mouse blood leukocytes in vivo after variable, low-dose rate exposure.\" 89 (2020)","DOI":"10.1007\/s00411-019-00825-x"},{"key":"43","doi-asserted-by":"crossref","unstructured":"SA Ghandhi, L Smilenov, I Shuryak, et al.  \"Sci Rep.\"  9, \"Discordant gene responses to radiation in humans and mice and the role of hematopoietically humanized mice in the search for radiation biomarkers.\" 19434 (2019)","DOI":"10.1038\/s41598-019-55982-2"},{"key":"4","doi-asserted-by":"crossref","unstructured":"Q Wang, Y Lee, I Shuryak, et al.  \"Sci Rep.\"  10, \"Development of the FAST-DOSE assay system for high-throughput biodosimetry and radiation triage.\" 12716 (2020)","DOI":"10.1038\/s41598-020-69460-7"},{"key":"42","doi-asserted-by":"crossref","unstructured":"E Macaeva, M Mysara, WH De Vos, et al.  \"Int J Radiat Biol.\"  95, \"Gene expression-based biodosimetry for radiological incidents: assessment of dose and time after radiation exposure.\" 64 (2019)","DOI":"10.1080\/09553002.2018.1511926"},{"key":"14","unstructured":"S Li, X Lu, JB Feng, et al.  \"Biomed Environ Sci.\"  30, \"Identification and validation of candidate radiation-responsive genes for human biodosimetry.\" 834 (2017)"},{"key":"45","doi-asserted-by":"crossref","unstructured":"JP Williams, SL Brown, GE Georges, et al.  \"Radiat Res.\"  173, \"Animal models for medical countermeasures to radiation exposure.\" 557 (2010)","DOI":"10.1667\/RR1880.1"},{"key":"52","doi-asserted-by":"crossref","unstructured":"NI Ossetrova, P Stanton, K Krasnopolsky, et al.  \"Health Phys.\"  115, \"Biomarkers for radiation biodosimetry and injury assessment after mixed-field (neutron and gamma) radiation in the mouse total-body irradiation model.\" 727 (2018)","DOI":"10.1097\/HP.0000000000000938"},{"key":"44","doi-asserted-by":"crossref","unstructured":"VK Singh  and AO Olabisi  \"Expert Opin Drug Discov.\"  12, \"Nonhuman primates as models for the discovery and development of radiation countermeasures.\" 695 (2017)","DOI":"10.1080\/17460441.2017.1323863"},{"key":"20","doi-asserted-by":"crossref","unstructured":"AL DiCarlo, C Maher, JL Hick, et al.  \"Disaster Med Public Health Prep.\"  5, \"Radiation injury after a nuclear detonation: medical consequences and the need for scarce resources allocation.\" S32 (2011)","DOI":"10.1001\/dmp.2011.17"},{"key":"18","doi-asserted-by":"crossref","unstructured":"CN Coleman  and JF Koerner  \"Radiat Prot Dosimetry.\"  172, \"Biodosimetry: medicine, science, and systems to support the medical decision-maker following a large scale nuclear or radiation incident.\" 38 (2016)","DOI":"10.1093\/rpd\/ncw155"},{"key":"36","doi-asserted-by":"crossref","unstructured":"G Manning, S Kabacik, P Finnon, et al.  \"Int J Radiat Biol.\"  89, \"High and low dose responses of transcriptional biomarkers in ex vivo X-irradiated human blood.\" 512 (2013)","DOI":"10.3109\/09553002.2013.769694"},{"key":"13","doi-asserted-by":"crossref","unstructured":"G O'Brien, L Cruz-Garcia, M Majewski, et al.  \"Sci Rep.\"  8, \"FDXR is a biomarker of radiation exposure in vivo.\" 684 (2018)","DOI":"10.1038\/s41598-017-19043-w"},{"key":"24","doi-asserted-by":"crossref","unstructured":"Y Lee, M Pujol Canadell, I Shuryak, et al.  \"Sci Rep.\"  8, \"Candidate protein markers for radiation biodosimetry in the hematopoietically humanized mouse model.\" 13557 (2018)","DOI":"10.1038\/s41598-018-31740-8"},{"key":"40","doi-asserted-by":"publisher","unstructured":"M Port, P Ostheim, M Majewski, et al.  \"Radiat Res.\"  192, \"Rapid high-throughput diagnostic triage after a mass radiation exposure event using early gene expression changes.\" 208 (2019)","DOI":"10.1667\/RR15360.1"},{"key":"32","doi-asserted-by":"crossref","unstructured":"H Budworth, AM Snijders, F Marchetti, et al.  \"PLoS One.\"  7, \"DNA repair and cell cycle biomarkers of radiation exposure and inflammation stress in human blood.\" e48619 (2012)","DOI":"10.1371\/journal.pone.0048619"},{"key":"31","doi-asserted-by":"crossref","unstructured":"WF Blakely, Z Carr, MC Chu, et al.  \"Radiat Res.\"  171, \"WHO 1st consultation on the development of a global biodosimetry laboratories network for radiation emergencies (BioDoseNet).\" 127 (2009)","DOI":"10.1667\/RR1549.1"},{"key":"37","doi-asserted-by":"crossref","unstructured":"S Li, X Lu, JB Feng, et al.  \"Radiat Res.\"  192, \"Developing gender-specific gene expression biodosimetry using a panel of radiation-responsive genes for determining radiation dose in human peripheral blood.\" 399 (2019)","DOI":"10.1667\/RR15355.1"},{"key":"1","doi-asserted-by":"crossref","unstructured":"MM Satyamitra, AL Dicarlo, BA Hollingsworth, et al.  \"Radiat Res.\"  197, \"Development of biomarkers for radiation biodosimetry and medical countermeasures research: Current status, utility, and regulatory pathways.\" 514 (2022)","DOI":"10.1667\/RADE-21-00157.1"},{"key":"2","doi-asserted-by":"crossref","unstructured":"V Meineke  and TM Fliedner  \"Br J Radiol.\"  78, \"Radiation-induced multi-organ involvement and failure: challenges for radiation accident medical management and future research.\" 196 (2014)","DOI":"10.1259\/bjr\/25654769"},{"key":"3","unstructured":"CJ Capaccio  and RJ Kowalski  \"Genotoxicity assay with cytoplasm boundary labeling.\""},{"key":"5","doi-asserted-by":"crossref","unstructured":"L Nemzow, T Boehringer, B Bacon, et al.  \"PLoS One.\"  18, \"Development of a human peripheral blood ex vivo model for rapid protein biomarker detection and applications to radiation biodosimetry.\" e0289634 (2023)","DOI":"10.1371\/journal.pone.0289634"},{"key":"7","doi-asserted-by":"crossref","unstructured":"MR Eman, E Regan-Klapisz, MW Pinkse, et al.  \"Electrophoresis.\"  27, \"Protein expression dynamics during replicative senescence of endothelial cells studied by 2-D difference in-gel electrophoresis.\" 1669 (2006)","DOI":"10.1002\/elps.200500746"},{"key":"8","doi-asserted-by":"crossref","unstructured":"JF Dierick, DE Kalume, F Wenders, et al.  \"FEBS Lett.\"  531, \"Identification of 30 protein species involved in replicative senescence and stress-induced premature senescence.\" 499 (2002)","DOI":"10.1016\/S0014-5793(02)03604-9"},{"key":"9","doi-asserted-by":"crossref","unstructured":"A Pe\u00f1a-Blanco  and AJ Garc\u00eda-S\u00e1ez  \"FEBS J.\"  285, \"Bax, Bak and beyond - mitochondrial performance in apoptosis.\" 416 (2018)","DOI":"10.1111\/febs.14186"},{"key":"10","unstructured":"S Kitada, S Krajewski, T Miyashita, et al.  \"Oncogene.\"  12, \"Gamma-radiation induces upregulation of Bax protein and apoptosis in radiosensitive cells in vivo.\" 187 (1996)"},{"key":"11","doi-asserted-by":"crossref","unstructured":"D Plesca, S Mazumder, A Almasan,  \"Meth Enzymol.\"  446, \"DNA damage response and apoptosis.\" 107 (2008)","DOI":"10.1016\/S0076-6879(08)01606-6"},{"key":"12","doi-asserted-by":"crossref","unstructured":"T Stoyanova, N Roy, D Kopanja, et al.  \"Cell Cycle.\"  8, \"DDB2 (damaged-DNA binding protein 2) in nucleotide excision repair and DNA damage response.\" 4067 (2009)","DOI":"10.4161\/cc.8.24.10109"},{"key":"15","doi-asserted-by":"crossref","unstructured":"KP Tao, SW Fong, Z Lu, et al.  \"PLoS One.\"  6, \"TSPYL2 is important for G1 checkpoint maintenance upon DNA damage.\" e21602 (2011)","DOI":"10.1371\/journal.pone.0021602"},{"key":"17","doi-asserted-by":"crossref","unstructured":"I Maci\u00e0, M Garau, A Lucas Calduch, et al.  \"Rep Pract Oncol Radiother.\"  16, \"Radiobiology of the acute radiation syndrome.\" 123 (2011)","DOI":"10.1016\/j.rpor.2011.06.001"},{"key":"21","doi-asserted-by":"crossref","unstructured":"A Pantelias  and GI Terzoudi  \"Mutat Res.\"  836, \"Development of an automatable micro-PCC biodosimetry assay for rapid individualized risk assessment in large-scale radiological emergencies.\" 65 (2018)","DOI":"10.1016\/j.mrgentox.2018.05.013"},{"key":"22","doi-asserted-by":"crossref","unstructured":"JS Greenberger  and M Epperly  \"Semin Radiat Oncol.\"  19, \"Bone marrow-derived stem cells and radiation response.\" 133 (2009)","DOI":"10.1016\/j.semradonc.2008.11.006"},{"key":"23","doi-asserted-by":"crossref","unstructured":"KD Thrall, J Lovaglio, MK Murphy, et al.  \"Health Phys.\"  105, \"A dose-dependent hematological evaluation of whole-body gamma-irradiation in the G\u00f6ttingen minipig.\" 245 (2013)","DOI":"10.1097\/HP.0b013e31829253a1"},{"key":"25","doi-asserted-by":"crossref","unstructured":"SR Amend, KC Valkenburg, KJ Pienta,  \"J Vis Exp.\"  110, \"Murine hind limb long bone dissection and bone marrow isolation.\" 53936 (2016)","DOI":"10.3791\/53936-v"},{"key":"26","doi-asserted-by":"crossref","unstructured":"D Hoehn, M Pujol-Canadell, EF Young, et al.  \"Radiat Res.\"  191, \"Effects of high- and low-LET radiation on human hematopoietic system reconstituted in immunodeficient mice.\" 162 (2019)","DOI":"10.1667\/RR15148.1"},{"key":"27","doi-asserted-by":"crossref","unstructured":"S Doulatov, F Notta, K Eppert, et al.  \"Nat Immunol.\"  11, \"Revised map of the human progenitor hierarchy shows the origin of macrophages and dendritic cells in early lymphoid development.\" 585 (2010)","DOI":"10.1038\/ni.1889"},{"key":"33","doi-asserted-by":"crossref","unstructured":"J Hall, PA Jeggo, C West, et al.  \"Mutat Res Rev Mut Res.\"  771, \"Ionizing radiation biomarkers in epidemiological studies - An update.\" 59 (2017)","DOI":"10.1016\/j.mrrev.2017.01.001"},{"key":"34","doi-asserted-by":"crossref","unstructured":"EB Golden, I Pellicciotta, S Demaria, et al.  \"Fron Oncol.\"  2, \"The convergence of radiation and immunogenic cell death signaling pathways.\" 88 (2012)","DOI":"10.3389\/fonc.2012.00088"},{"key":"35","doi-asserted-by":"crossref","unstructured":"NC Walsh, LL Kenney, S Jangalwe, et al.  \"Annu Rev Pathol.\"  12, \"Humanized mouse models of clinical disease.\" 187 (2017)","DOI":"10.1146\/annurev-pathol-052016-100332"},{"key":"38","doi-asserted-by":"crossref","unstructured":"K Brz\u00f3ska  and M Kruszewski  \"Radiat Environ Biophys.\"  54, \"Toward the development of transcriptional biodosimetry for the identification of irradiated individuals and assessment of absorbed radiation dose.\" 353 (2015)","DOI":"10.1007\/s00411-015-0603-8"},{"key":"39","doi-asserted-by":"crossref","unstructured":"M Abend, WF Blakely, P Ostheim, et al.  \"J Radiol Prot.\"  2022, \"Early molecular markers for retrospective biodosimetry and prediction of acute health effects.\" 42","DOI":"10.1088\/1361-6498\/ac2434"},{"key":"41","doi-asserted-by":"crossref","unstructured":"P Ostheim, SA Amundson, C Badie, et al.  \"Int J Radiat Biol.\"  98, \"Gene expression for biodosimetry and effect prediction purposes: promises, pitfalls and future directions - key session ConRad 2021.\" 843 (2022)","DOI":"10.1080\/09553002.2021.1987571"},{"key":"46","doi-asserted-by":"crossref","unstructured":"JA Spencer, F Ferraro, E Roussakis, et al.  \"Nature.\"  508, \"Direct measurement of local oxygen concentration in the bone marrow of live animals.\" 269 (2014)","DOI":"10.1038\/nature13034"},{"key":"47","doi-asserted-by":"crossref","unstructured":"L Shao, Y Luo, DJA Zhou,  \"Antioxid Redox Signal.\"  20, \"Hematopoietic stem cell injury induced by ionizing radiation.\" 1447 (2014)","DOI":"10.1089\/ars.2013.5635"},{"key":"48","doi-asserted-by":"crossref","unstructured":"CL Herd, J Mellet, T Mashingaidze, et al.  \"Front Immunol.\"  14, \"Consequences of HIV infection in the bone marrow niche.\" 1163012 (2023)","DOI":"10.3389\/fimmu.2023.1163012"},{"key":"49","doi-asserted-by":"crossref","unstructured":"Y Wang, BA Schulte, D Zhou,  \"Cell Cycle.\"  5, \"Hematopoietic stem cell senescence and long-term bone marrow injury.\" 35 (2006)","DOI":"10.4161\/cc.5.1.2280"},{"key":"50","doi-asserted-by":"crossref","unstructured":"EN Bogd\u00e1ndi, A Balogh, N Felgyinszki, et al.  \"Radiat Res.\"  174, \"Effects of low-dose radiation on the immune system of mice after total-body irradiation.\" 480 (2010)","DOI":"10.1667\/RR2160.1"},{"key":"51","doi-asserted-by":"crossref","unstructured":"EL Kachikwu, KS Iwamoto, Y-P Liao, et al.  \"Int J Radiat.\"  81, \"Radiation enhances regulatory T cell representation.\" 1128 (2011)","DOI":"10.1016\/j.ijrobp.2010.09.034"},{"key":"54","doi-asserted-by":"publisher","unstructured":"A Gibbs, P Gupta, B Mali, et al.  \"Radiat Res.\"  199, \"A C57L\/J mouse model of the delayed effects of acute radiation exposure in the context of evolving multi-organ dysfunction and failure after total-body irradiation with 2.5% bone marrow sparing.\" 319 (2023)","DOI":"10.1667\/RADE-22-00178.1"},{"key":"19","doi-asserted-by":"crossref","unstructured":"TA Winters, DR Cassatt, JR Harrison-Peters, et al.  \"Radiat Res.\"  199, \"Considerations of medical preparedness to assess and treat various populations during a radiation public health emergency.\" 301 (2023)","DOI":"10.1667\/RADE-22-00148.1"},{"key":"16","doi-asserted-by":"crossref","unstructured":"TA Winters, DR Cassatt, JR Harrison-Peters, et al.  \"Radiat Res.\"  199, \"Considerations of medical preparedness to assess and treat various populations during a radiation public health emergency.\" 301 (2023)","DOI":"10.1667\/RADE-22-00148.1"},{"key":"6","doi-asserted-by":"crossref","unstructured":"I Shuryak, L Nemzow, BA Bacon, et al.  \"Sci Rep.\"  13, \"Machine learning approach for quantitative biodosimetry of partial-body or total-body radiation exposures by combining radiation-responsive biomarkers.\" 949 (2023)","DOI":"10.1038\/s41598-023-28130-0"}],"container-title":["Radiation Research"],"original-title":[],"link":[{"URL":"https:\/\/meridian.allenpress.com\/radiation-research\/article-pdf\/doi\/10.1667\/RADE-24-00049.1\/3402508\/10.1667_rade-24-00049.1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/meridian.allenpress.com\/radiation-research\/article-pdf\/doi\/10.1667\/RADE-24-00049.1\/3402508\/10.1667_rade-24-00049.1.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T00:25:49Z","timestamp":1791246349000},"score":1,"resource":{"primary":{"URL":"https:\/\/bioone.org\/journals\/radiation-research\/volume-202\/issue-3\/RADE-24-00049.1\/Biomarkers-for-Radiation-Biodosimetry-and-Correlation-with-Hematopoietic-Injury-in\/10.1667\/RADE-24-00049.1.full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,7,22]]},"references-count":54,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2024,9,1]]}},"URL":"https:\/\/doi.org\/10.1667\/rade-24-00049.1","relation":{},"ISSN":["0033-7587","1938-5404"],"issn-type":[{"value":"0033-7587","type":"print"},{"value":"1938-5404","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,7,22]]}}}