{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T12:32:33Z","timestamp":1793449953375,"version":"4.5.0"},"reference-count":49,"publisher":"Radiation Research Society","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Radiation Research"],"published-print":{"date-parts":[[2020,4,13]]},"abstract":"<jats:p>In the event of a mass casualty radiation scenario, rapid assessment of patients' health and triage is required for optimal resource utilization. Identifying the level and extent of exposure as well as prioritization of care is extremely challenging under such disaster conditions. Blood-based biomarkers, such as RNA integrity numbers (RIN), could help healthcare personnel quickly and efficiently determine the extent and effect of multiple injuries on patients' health. Evaluation of the effect of different radiation doses, alone or in combination with burn injury, on total RNA integrity over multiple time points was performed. Total RNA integrity was tallied in blood samples for potential application as a marker of radiation exposure and survival. Groups of aged mice (3\u20136 mice\/group, 13\u201318 months old) received 0.5, 1, 5, 10 or 20 Gy ionizing radiation. Two additional mouse groups received low-dose irradiation (0.5 or 1 Gy) with a 15% total body surface area (TBSA) burn injury. Animals were euthanized at 2 or 12 h and at day 1, 2, 3, 7 or 14 postirradiation, or when injury-mediated mortality occurred. Total RNA was isolated from blood. The quality of RNA was evaluated and RNA RIN were obtained. Analysis of RIN indicated that blood showed the clearest radiation effect. There was a time- and radiation-dose-dependent reduction in RIN that was first detectable at 12 h postirradiation for all doses in animals receiving irradiation alone. This effect was reversible in lower-dose groups (i.e., 0.5, 1 and 5 Gy) that survived to the end of the study (14 days). In contrast, the effect persisted for 10 and 20 Gy groups, which showed suppression of RIN values &lt;4.5 with high mortalities. Radiation doses of 20 Gy were lethal and required euthanasia by day 6. A low RIN (&lt;2.5) at any time point was associated with 100% mortality. Combined radiation-burn injury produced significantly increased mortality such that no dually-injured animals survived beyond day 3, and no radiation dose &gt;1 Gy resulted in survival past day 1. More modest suppression of RIN was observed in the surviving dually challenged mice, and no statistically significant changes were identified in RIN values of burn-only mice at any time point. In this study of an animal model, a proof of concept is presented for a simple and accurate method of assessing radiation dose exposure in blood which potentially predicts lethality. RIN assessment of blood-derived RNA could form the basis for a clinical decision-support tool to guide healthcare providers under the strenuous conditions of a radiation-based mass casualty event.<\/jats:p>","DOI":"10.1667\/rr15527.1","type":"journal-article","created":{"date-parts":[[2020,4,13]],"date-time":"2020-04-13T15:06:58Z","timestamp":1586790418000},"page":"543-551","source":"Crossref","is-referenced-by-count":4,"title":["Blood RNA Integrity is a Direct and Simple Reporter of Radiation Exposure and Prognosis: A Pilot Study"],"prefix":"10.1667","volume":"193","author":[{"given":"Abdulnaser","family":"Alkhalil","sequence":"first","affiliation":[{"name":"Firefighters' Burn and Surgical Research Laboratory, MedStar Health Research Institute, Washington, DC 20010"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John. L.","family":"Clifford","sequence":"additional","affiliation":[{"name":"Integrative Systems Biology Program, U.S. Army Center for Environmental Health Research, Fort Detrick, Maryland 21702"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Ball","sequence":"additional","affiliation":[{"name":"Firefighters' Burn and Surgical Research Laboratory, MedStar Health Research Institute, Washington, DC 20010"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Day","sequence":"additional","affiliation":[{"name":"Firefighters' Burn and Surgical Research Laboratory, MedStar Health Research Institute, Washington, DC 20010"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosanna","family":"Chan","sequence":"additional","affiliation":[{"name":"The Burn Department of Radiology, MedStar Washington Hospital Center, Washington, DC 20010"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bonnie C.","family":"Carney","sequence":"additional","affiliation":[{"name":"Firefighters' Burn and Surgical Research Laboratory, MedStar Health Research Institute, Washington, DC 20010"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stacy Ann","family":"Miller","sequence":"additional","affiliation":[{"name":"Integrative Systems Biology, The Oak Ridge Institute for Science and Education, Fort Detrick, Maryland 21702-5000"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ross","family":"Campbell","sequence":"additional","affiliation":[{"name":"Integrative Systems Biology Program, U.S. Army Center for Environmental Health Research, Fort Detrick, Maryland 21702"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raina","family":"Kumar","sequence":"additional","affiliation":[{"name":"Integrative Systems Biology Program, U.S. Army Center for Environmental Health Research, Fort Detrick, Maryland 21702"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aarti","family":"Gautam","sequence":"additional","affiliation":[{"name":"Integrative Systems Biology Program, U.S. Army Center for Environmental Health Research, Fort Detrick, Maryland 21702"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rasha","family":"Hammamieh","sequence":"additional","affiliation":[{"name":"Integrative Systems Biology Program, U.S. Army Center for Environmental Health Research, Fort Detrick, Maryland 21702"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauren T.","family":"Moffatt","sequence":"additional","affiliation":[{"name":"Firefighters' Burn and Surgical Research Laboratory, MedStar Health Research Institute, Washington, DC 20010"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey W.","family":"Shupp","sequence":"additional","affiliation":[{"name":"Firefighters' Burn and Surgical Research Laboratory, MedStar Health Research Institute, Washington, DC 20010"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1243","reference":[{"key":"35","doi-asserted-by":"crossref","unstructured":"PR Almond, PJ Biggs, BM Coursey, et al.  \"Med Phys.\"  26, \"AAPM's TG-51 protocol for clinical reference dosimetry of high-energy photon and electron beams.\" 1847 (1999)","DOI":"10.1118\/1.598691"},{"key":"1","unstructured":"JW. Gofman,  \"Radiation and human health.\"  ,  (1981)"},{"key":"2","doi-asserted-by":"crossref","unstructured":"NE. Bolus,  \"J Nucl Med Technol.\"  45, \"Basic review of radiation biology and terminology.\" 259 (2017)","DOI":"10.2967\/jnmt.117.195230"},{"key":"3","doi-asserted-by":"crossref","unstructured":"JD Boice,  \"Health Phys.\"  106, \"Implications of radiation dose and exposed populations on radiation protection in the 21st century.\" 313 (2014)","DOI":"10.1097\/HP.0000000000000024"},{"key":"4","doi-asserted-by":"crossref","unstructured":"M Ghardi, M Moreels, B Chatelain, et al.  \"Int J Mol Med.\"  29, \"Radiation-induced double strand breaks and subsequent apoptotic DNA fragmentation in human peripheral blood mononuclear cells.\" 769 (2012)","DOI":"10.3892\/ijmm.2012.907"},{"key":"5","doi-asserted-by":"crossref","unstructured":"EC Bourton, PN Plowman, D Smith, et al.  \"Int J Cancer.\"  129, \"Prolonged expression of the gamma-H2AX DNA repair biomarker correlates with excess acute and chronic toxicity from radiotherapy treatment.\" 2928 (2011)","DOI":"10.1002\/ijc.25953"},{"key":"6","doi-asserted-by":"crossref","unstructured":"A Ivashkevich, CE Redon, AJ Nakamura, et al.  \"Cancer Lett.\"  327, \"Use of the gamma-H2AX assay to monitor DNA damage and repair in translational cancer research.\" 123 (2012)","DOI":"10.1016\/j.canlet.2011.12.025"},{"key":"7","doi-asserted-by":"crossref","unstructured":"CE Redon, AJ Nakamura, OA Martin, et al.  \"Aging.\"  3, \"Recent developments in the use of gamma-H2AX as a quantitative DNA double-strand break biomarker.\" 168 (2011)","DOI":"10.18632\/aging.100284"},{"key":"8","doi-asserted-by":"crossref","unstructured":"IR Miousse, KR Kutanzi, I Koturbash,  \"Int J Radiat Biol.\"  93, \"Effects of ionizing radiation on DNA methylation: from experimental biology to clinical applications.\" 457 (2017)","DOI":"10.1080\/09553002.2017.1287454"},{"key":"9","doi-asserted-by":"crossref","unstructured":"TW Lhakhang  and MA Chaudhry  \"Comp Funct Genomics.\"  2012, \"Interactome of radiation-induced microRNA-predicted target genes.\" 569731 (2012)","DOI":"10.1155\/2012\/569731"},{"key":"10","doi-asserted-by":"crossref","unstructured":"M Halimi, H Parsian, SM Asghari, et al.  \"Transl Res.\"  163, \"Clinical translation of human microRNA 21 as a potential biomarker for exposure to ionizing radiation.\" 578 (2014)","DOI":"10.1016\/j.trsl.2014.01.009"},{"key":"11","doi-asserted-by":"crossref","unstructured":"RL Warters, DL Williams, SB Zhuplatov, et al.  \"Radiat Res.\"  168, \"Protein phosphorylation in irradiated human melanoma cells.\" 535 (2007)","DOI":"10.1667\/RR0404.1"},{"key":"12","doi-asserted-by":"crossref","unstructured":"A Turtoi, RN Sharan, A Srivastava, et al.  \"Int J Radiat Biol.\"  86, \"Proteomic and genomic modulations induced by gamma irradiation of human blood lymphocytes.\" 888 (2010)","DOI":"10.3109\/09553002.2010.486016"},{"key":"13","doi-asserted-by":"crossref","unstructured":"JG Kiang  and AO Olabisi  \"Cell Biosci.\"  9, \"Radiation: a poly-traumatic hit leading to multi-organ injury.\" 25 (2019)","DOI":"10.1186\/s13578-019-0286-y"},{"key":"14","doi-asserted-by":"crossref","unstructured":"KS Breger, L Smith, MS Turker, et al.  \"Cancer Res.\"  64, \"Ionizing radiation induces frequent translocations with delayed replication and condensation.\" 8231 (2004)","DOI":"10.1158\/0008-5472.CAN-04-0879"},{"key":"15","doi-asserted-by":"crossref","unstructured":"Y Abe, MA Yoshida, K Fujioka, et al.  \"J Radiat Res.\"  59, \"Dose-response curves for analyzing of dicentric chromosomes and chromosome translocations following doses of 1000 mGy or less, based on irradiated peripheral blood samples from five healthy individuals.\" 35 (2018)","DOI":"10.1093\/jrr\/rrx052"},{"key":"16","doi-asserted-by":"crossref","unstructured":"SD Bouffler, MA Blasco, R Cox, et al.  \"Int J Radiat Biol.\"  77, \"Telomeric sequences, radiation sensitivity and genomic instability.\" 995 (2001)","DOI":"10.1080\/09553000110069326"},{"key":"17","doi-asserted-by":"crossref","unstructured":"X Zhang, C Ye, F Sun, et al.  \"PloS One.\"  11, \"Both complexity and location of DNA damage contribute to cellular senescence induced by ionizing radiation.\" e0155725 (2016)","DOI":"10.1371\/journal.pone.0155725"},{"key":"18","doi-asserted-by":"crossref","unstructured":"MF Arlt, S Rajendran, SR Birkeland, et al.  \"Environ Mol Mutagen.\"  55, \"Copy number variants are produced in response to low-dose ionizing radiation in cultured cells.\" 103 (2014)","DOI":"10.1002\/em.21840"},{"key":"19","doi-asserted-by":"crossref","unstructured":"YW Jin, YJ Na, YJ Lee, et al.  \"Oncol Rep.\"  19, \"Comprehensive analysis of time- and dose-dependent patterns of gene expression in a human mesenchymal stem cell line exposed to low-dose ionizing radiation.\" 135 (2008)","DOI":"10.3892\/or.19.1.135"},{"key":"20","doi-asserted-by":"crossref","unstructured":"EL Pannkuk, AJ Fornace, EC Laiakis,  \"Int J Radiat Biol.\"  93, \"Metabolomic applications in radiation biodosimetry: exploring radiation effects through small molecules.\" 1151 (2017)","DOI":"10.1080\/09553002.2016.1269218"},{"key":"21","doi-asserted-by":"crossref","unstructured":"CH Johnson, AD Patterson, KW Krausz, et al.  \"Radiat Res.\"  178, \"Radiation metabolomics. 5. Identification of urinary biomarkers of ionizing radiation exposure in nonhuman primates by mass spectrometry-based metabolomics.\" 328 (2012)","DOI":"10.1667\/RR2950.1"},{"key":"22","doi-asserted-by":"crossref","unstructured":"EA Ainsbury, E Bakhanova, JF Barquinero, et al.  \"Radiat Prot Dosimetry.\"  147, \"Review of retrospective dosimetry techniques for external ionising radiation exposures.\" 573 (2011)","DOI":"10.1093\/rpd\/ncq499"},{"key":"23","doi-asserted-by":"crossref","unstructured":"AW Hsie, PA Brimer, TJ Mitchell, et al.  \"Somatic Cell Genet.\"  1, \"The dose-response relationship for ultraviolet-light-induced mutations at the hypoxanthine-guanine phosphoribosyltransferase locus in Chinese hamster ovary cells.\" 383 (1975)","DOI":"10.1007\/BF01538669"},{"key":"24","doi-asserted-by":"crossref","unstructured":"J Cadet  and JR Wagner  \"Cold Spring Harb Perspect Biol.\"  5, \"DNA base damage by reactive oxygen species, oxidizing agents, and UV radiation.\"  (2013)","DOI":"10.1101\/cshperspect.a012559"},{"key":"25","doi-asserted-by":"crossref","unstructured":"R Neta  and JJ Oppenheim  \"Blood.\"  72, \"Cytokines in therapy of radiation injury.\" 1093 (1988)","DOI":"10.1182\/blood.V72.3.1093.1093"},{"key":"26","doi-asserted-by":"crossref","unstructured":"JG Bazan, P Chang, R Balog, et al.  \"Int J Radiat Oncol Biol Phys.\"  90, \"Novel human radiation exposure biomarker panel applicable for population triage.\" 612 (2014)","DOI":"10.1016\/j.ijrobp.2014.05.046"},{"key":"27","doi-asserted-by":"crossref","unstructured":"A Wygoda, JJ Mrochem-Kwarciak, M Kentnowski, et al.  \"Int J Radiat Oncol Biol Phys.\"  94, \"C-reactive protein as a biomarker of radiation therapy and chemotherapy toxicity monitoring in patients with head and neck cancer.\" 905 (2016)","DOI":"10.1016\/j.ijrobp.2015.12.121"},{"key":"29","doi-asserted-by":"crossref","unstructured":"JL Palmer, CR Deburghgraeve, MD Bird, et al.  \"J Burn Care Res.\"  32, \"Development of a combined radiation and burn injury model.\" 317 (2011)","DOI":"10.1097\/BCR.0b013e31820aafa9"},{"key":"30","doi-asserted-by":"crossref","unstructured":"EA Carter, D Winter, C Tolman, et al.  \"J Burn Care Res.\"  33, \"Combination of radiation and burn injury alters [(1)(8)F] 2-fluoro-2-deoxy-D-glucose uptake in mice.\" 723 (2012)","DOI":"10.1097\/BCR.0b013e31825d678f"},{"key":"31","doi-asserted-by":"crossref","unstructured":"JK Chai, W Liu, HP Deng, et al.  \"Shock.\"  40, \"A novel model of burn-blast combined injury and its phasic changes of blood coagulation in rats.\" 297 (2013)","DOI":"10.1097\/SHK.0b013e3182837831"},{"key":"32","doi-asserted-by":"crossref","unstructured":"AE Mendoza, CJ Neely, AG Charles, et al.  \"Shock.\"  38, \"Radiation combined with thermal injury induces immature myeloid cells.\" 532 (2012)","DOI":"10.1097\/SHK.0b013e31826c5b19"},{"key":"33","doi-asserted-by":"crossref","unstructured":"P Foubert, M Doyle-Eisele, A Gonzalez, et al.  \"Int J Radiat Biol.\"  93, \"Development of a combined radiation and full thickness burn injury minipig model to study the effects of uncultured adipose-derived regenerative cell therapy in wound healing.\" 340 (2017)","DOI":"10.1080\/09553002.2017.1242814"},{"key":"34","doi-asserted-by":"crossref","unstructured":"A Schroeder, O Mueller, S Stocker, et al.  \"BMC Mol Biol.\"  7, \"The RIN: an RNA integrity number for assigning integrity values to RNA measurements.\" 3 (2006)","DOI":"10.1186\/1471-2199-7-3"},{"key":"36","unstructured":"JN Luker, M Vigiola Cruz, BC Carney, et al.  \"Ann Burns Fire Disasters.\"  31, \"Shedding of the endothelial glycocalyx is quantitatively proportional to burn injury severity.\" 17 (2018)"},{"key":"37","doi-asserted-by":"crossref","unstructured":"M Vigiola Cruz, BC Carney, JN Luker, et al.  \"J Surg Res.\"  233, \"Plasma ameliorates endothelial dysfunction in burn injury.\" 459 (2019)","DOI":"10.1016\/j.jss.2018.08.027"},{"key":"38","doi-asserted-by":"crossref","unstructured":"D Belpomme, P Irigaray, L Hardell, et al.  \"Environ Res.\"  105, \"The multitude and diversity of environmental carcinogens.\" 414 (2007)","DOI":"10.1016\/j.envres.2007.07.002"},{"key":"39","doi-asserted-by":"crossref","unstructured":"M Macia I Garau, A Lucas Calduch, EC Lopez,  \"Rep Pract Oncol Radiother.\"  16, \"Radiobiology of the acute radiation syndrome.\" 123 (2011)","DOI":"10.1016\/j.rpor.2011.06.001"},{"key":"40","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":"41","doi-asserted-by":"crossref","unstructured":"NI Ossetrova, P Stanton, K Krasnopolsky, et al.  \"Health Phys.\"  115, \"Comparison of biodosimetry biomarkers for radiation dose and injury assessment after mixed-field (neutron and gamma) and pure gamma radiation in the mouse total-body irradiation model.\" 743 (2018)","DOI":"10.1097\/HP.0000000000000939"},{"key":"42","doi-asserted-by":"crossref","unstructured":"JG Kiang, JT Smith, SR Hegge, et al.  \"Radiat Res.\"  189, \"Circulating cytokine\/chemokine concentrations respond to ionizing radiation doses but not radiation dose rates: granulocyte-colony stimulating factor and interleukin-18.\" 634 (2018)","DOI":"10.1667\/RR14966.1"},{"key":"43","doi-asserted-by":"crossref","unstructured":"MD Wouters, DC van Gent, JH Hoeijmakers, et al.  \"Mutat Res.\"  717, \"Micro-RNAs, the DNA damage response and cancer.\" 54 (2011)","DOI":"10.1016\/j.mrfmmm.2011.03.012"},{"key":"44","doi-asserted-by":"crossref","unstructured":"BL Mahaney, K Meek, SP Lees-Miller,  \"Biochem J.\"  417, \"Repair of ionizing radiation-induced DNA double-strand breaks by non-homologous end-joining.\" 639 (2009)","DOI":"10.1042\/BJ20080413"},{"key":"45","doi-asserted-by":"crossref","unstructured":"CR Hunt, D Ramnarain, N Horikoshi, et al.  \"Radiat Res.\"  179, \"Histone modifications and DNA double-strand break repair after exposure to ionizing radiations.\" 383 (2013)","DOI":"10.1667\/RR3308.2"},{"key":"46","doi-asserted-by":"crossref","unstructured":"RK Sachs, LR Hlatky, BJ Trask,  \"Trends Genet.\"  16, \"Radiation-produced chromosome aberrations: colourful clues.\" 143 (2000)","DOI":"10.1016\/S0168-9525(99)01960-5"},{"key":"47","doi-asserted-by":"crossref","unstructured":"C Lavelle  and N Foray  \"Int J Biochem Cell Biol.\"  49, \"Chromatin structure and radiation-induced DNA damage: From structural biology to radiobiology.\" 84 (2014)","DOI":"10.1016\/j.biocel.2014.01.012"},{"key":"48","doi-asserted-by":"crossref","unstructured":"Z. Somosy,  \"Micron.\"  31, \"Radiation response of cell organelles.\" 165 (2000)","DOI":"10.1016\/S0968-4328(99)00083-9"},{"key":"49","doi-asserted-by":"crossref","unstructured":"JG Kiang, M Zhai, P-J Liao, et al.  \"Oxid Med Cell Longev.\"  2014, \"Ghrelin therapy improves survival after whole-body ionizing irradiation or combined with burn or wound: amelioration of leukocytopenia, thrombocytopenia, splenomegaly, and bone marrow injury.\" 215858 (2014)","DOI":"10.1155\/2014\/215858"},{"key":"28","doi-asserted-by":"crossref","unstructured":"E Pernot, J Hall, S Baatout, et al.  \"Mutat Res.\"  751, \"Ionizing radiation biomarkers for potential use in epidemiological studies.\" 258 (2012)","DOI":"10.1016\/j.mrrev.2012.05.003"}],"container-title":["Radiation Research"],"original-title":[],"deposited":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T11:55:34Z","timestamp":1793447734000},"score":1,"resource":{"primary":{"URL":"https:\/\/bioone.org\/journals\/radiation-research\/volume-193\/issue-6\/RR15527.1\/Blood-RNA-Integrity-is-a-Direct-and-Simple-Reporter-of\/10.1667\/RR15527.1.full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,4,13]]},"references-count":49,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2020,6,1]]}},"URL":"https:\/\/doi.org\/10.1667\/rr15527.1","relation":{},"ISSN":["0033-7587","1938-5404"],"issn-type":[{"value":"0033-7587","type":"print"},{"value":"1938-5404","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,4,13]]}}}