{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T11:31:32Z","timestamp":1793446292864,"version":"4.5.0"},"reference-count":52,"publisher":"Radiation Research Society","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Radiation Research"],"published-print":{"date-parts":[[2020,9,16]]},"abstract":"<jats:p>In the event of a major accidental or intentional radiation exposure incident, the affected population could suffer from total- or partial-body exposures to ionizing radiation with acute exposure to organs that would produce life-threatening injury. Therefore, it is necessary to identify markers capable of predicting organ-specific damage so that appropriate directed or encompassing therapies can be applied. In the current work, gene expression changes in response to total-body irradiation (TBI) were identified in heart, lungs and liver tissue of G\u00f6ttingen minipigs. Animals received 1.7, 1.9, 2.1 or 2.3 Gy TBI and were followed for 45 days. Organ samples were collected at the end of day 45 or sooner if the animal displayed morbidity necessitating euthanasia. Our findings indicate that different organs respond to TBI in a very specific and distinct manner. We also found that the liver was the most affected organ in terms of gene expression changes, and that lipid metabolic pathways were the most deregulated in the liver samples of non-survivors (survival time &lt;45 days). We identified organ-specific gene expression signatures that accurately differentiated non-survivors from survivors and control animals, irrespective of dose and time postirradiation. At what point did these radiation-induced injury markers manifest and how this information could be used for applying intervention therapies are under investigation.<\/jats:p>","DOI":"10.1667\/rade-20-00123.1","type":"journal-article","created":{"date-parts":[[2020,10,2]],"date-time":"2020-10-02T06:30:32Z","timestamp":1601620232000},"page":"411-430","source":"Crossref","is-referenced-by-count":18,"title":["Gene Expression Profiles from Heart, Lung and Liver Samples of Total-Body-Irradiated Minipigs: Implications for Predicting Radiation-Induced Tissue Toxicity"],"prefix":"10.1667","volume":"194","author":[{"given":"Sunita","family":"Chopra","sequence":"first","affiliation":[{"name":"Radiation Oncology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Moroni","sequence":"additional","affiliation":[{"name":"Radiation Countermeasures Program, Armed Forces Radiobiology Research Institute, Uniformed Services University of the Health Sciences, Bethesda, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shannon","family":"Martello","sequence":"additional","affiliation":[{"name":"Radiation Oncology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle","family":"Bylicky","sequence":"additional","affiliation":[{"name":"Radiation Oncology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jared","family":"May","sequence":"additional","affiliation":[{"name":"Radiation Oncology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernadette","family":"Hritzo","sequence":"additional","affiliation":[{"name":"Radiation Countermeasures Program, Armed Forces Radiobiology Research Institute, Uniformed Services University of the Health Sciences, Bethesda, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurel","family":"MacMillan","sequence":"additional","affiliation":[{"name":"Gryphon Scientific, Takoma Park, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C. Norman","family":"Coleman","sequence":"additional","affiliation":[{"name":"Radiation Oncology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Molykutty J.","family":"Aryankalayil","sequence":"additional","affiliation":[{"name":"Radiation Oncology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1243","reference":[{"key":"41","doi-asserted-by":"crossref","unstructured":"M Boerma, C Zurcher, I Esveldt, et al.  \"Oncol Rep.\"  12, \"Histopathology of ventricles, coronary arteries and mast cell accumulation in transverse and longitudinal sections of the rat heart after irradiation.\" 213 (2004)","DOI":"10.3892\/or.12.2.213"},{"key":"7","doi-asserted-by":"crossref","unstructured":"J Lucas, HK Dressman, S Suchindran, et al.  \"PLoS One.\"  9, \"A translatable predictor of human radiation 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blood serum of breast cancer patients as a potential triage biodosimeter for large-scale radiological emergencies.\" 555 (2014)","DOI":"10.1097\/HP.0000000000000158"},{"key":"11","doi-asserted-by":"crossref","unstructured":"JW Jones, A Bennett, CL Carter, et al.  \"Health Phys.\"  109, \"Citrulline as a biomarker in the non-human primate total-and partial-body irradiation models: Correlation of circulating citrulline to acute and prolonged gastrointestinal injury.\" 440 (2015)","DOI":"10.1097\/HP.0000000000000347"},{"key":"12","doi-asserted-by":"crossref","unstructured":"K Bujold, M Hauer-Jensen, O Donini, et al.  \"Radiat Res.\"  186, \"Citrulline as a biomarker for gastrointestinal-acute radiation syndrome: Species differences and experimental condition effects.\" 71 (2016)","DOI":"10.1667\/RR14305.1"},{"key":"13","doi-asserted-by":"crossref","unstructured":"M Phillips, RN Cataneo, A Chaturvedi, et al.  \"Health Phys.\"  108, \"Breath biomarkers of whole-body gamma irradiation in the G\u00f6ttingen minipig.\" 538 (2015)","DOI":"10.1097\/HP.0000000000000272"},{"key":"14","doi-asserted-by":"crossref","unstructured":"M Sproull, T Kramp, A Tandle, et al.  \"Radiat Res.\"  184, \"Serum amyloid A as a biomarker for radiation exposure.\" 14 (2015)","DOI":"10.1667\/RR13927.1"},{"key":"16","doi-asserted-by":"crossref","unstructured":"MJ Aryankalayil, S Chopra, J Levin, et al.  \"Radiat Res.\"  189, \"Radiation-induced long noncoding RNAs in a mouse model after whole-body irradiation.\" 251 (2018)","DOI":"10.1667\/RR14891.1"},{"key":"18","doi-asserted-by":"crossref","unstructured":"AR Jacobs, T Guyon, V Headley, et al.  \"Int J Radiat Biol.\"  96, \"Role of a high throughput biodosimetry test in treatment prioritization after a nuclear incident.\" 57 (2020)","DOI":"10.1080\/09553002.2018.1532615"},{"key":"21","unstructured":"et al.  \"Acute radiation syndrome.\"  ,  (2020)"},{"key":"22","doi-asserted-by":"crossref","unstructured":"Y Li, BC Shirley, RC Wilkins, et al.  \"Radiat Prot Dosimetry.\"  186, \"Radiation dose estimation by completely automated interpretation of the dicentric chromosome assay.\" 42 (2019)","DOI":"10.1093\/rpd\/ncy282"},{"key":"23","doi-asserted-by":"crossref","unstructured":"I Romero, O Garc\u00eda, AI Lamadrid, et al.  \"J Radiat Res.\"  54, \"Assessment of simulated high-dose partial-body irradiation by PCC-R assay.\" 863 (2013)","DOI":"10.1093\/jrr\/rrt032"},{"key":"24","doi-asserted-by":"crossref","unstructured":"AH Dorr, M Abend, WF Blakely, et al.  \"Radiat Res.\"  187, \"Using clinical signs and symptoms for medical management of radiation casualties \u2013 2015 NATO exercise.\" 273 (2017)","DOI":"10.1667\/RR14619.1"},{"key":"25","doi-asserted-by":"crossref","unstructured":"M Moroni, E Lombardini, R Salber, et al.  \"PLoS One.\"  6, \"Hematological changes as prognostic indicators of survival: Similarities between G\u00f6ttingen minipigs, humans, and other large animal models.\" e25210 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(2016)","DOI":"10.1371\/journal.pone.0156594"},{"key":"30","doi-asserted-by":"crossref","unstructured":"J Kim  and Y Jung  \"Exp Mol Med.\"  49, \"Radiation-induced liver disease: Current understanding and future perspectives.\" e359 (2017)","DOI":"10.1038\/emm.2017.85"},{"key":"31","doi-asserted-by":"crossref","unstructured":"P Munoz-Schuffenegger, S Ng, LA Dawson,  \"Semin Radiat Oncol.\"  27, \"Radiation-induced liver toxicity.\" 350 (2017)","DOI":"10.1016\/j.semradonc.2017.04.002"},{"key":"32","doi-asserted-by":"crossref","unstructured":"R Benson, R Madan, R Kilambi, et al.  \"J Egypt Natl Canc Inst.\"  28, \"Radiation induced liver disease: A clinical update.\" 7 (2016)","DOI":"10.1016\/j.jnci.2015.08.001"},{"key":"33","doi-asserted-by":"crossref","unstructured":"M V. Bakshi, O Azimzadeh, Z Barjaktarovic, et al.  \"J Proteome Res.\"  14, \"Total body exposure to low-dose ionizing radiation induces long-term alterations to the liver proteome of neonatally exposed mice.\" 366 (2015)","DOI":"10.1021\/pr500890n"},{"key":"34","doi-asserted-by":"crossref","unstructured":"K Kjaergaard, B Weber, AKO Alstrup, et al.  \"Sci Rep.\"  10, \"Hepatic regeneration following radiation-induced liver injury is associated with increased hepatobiliary secretion measured by PET in G\u00f6ttingen minipigs.\" 10858 (2020)","DOI":"10.1038\/s41598-020-67609-y"},{"key":"35","doi-asserted-by":"crossref","unstructured":"Z Huang, M Zhang, AA Plec, et al.  \"Proc Natl Acad Sci U S A.\"  115, \"ACSS2 promotes systemic fat storage and utilization through selective regulation of genes involved in lipid metabolism.\" E9499 (2018)","DOI":"10.1073\/pnas.1806635115"},{"key":"36","doi-asserted-by":"crossref","unstructured":"AM ALJohani, DN Syed, JM Ntambi,  \"Trends Endocrinol Metab.\"  28, \"Insights into stearoyl-CoA desaturase-1 regulation of systemic metabolism.\" 831 (2017)","DOI":"10.1016\/j.tem.2017.10.003"},{"key":"37","doi-asserted-by":"crossref","unstructured":"MB Wysocka, K Pietraszek-Gremplewicz, D Nowak,  \"Front Physiol.\"  9, \"The role of apelin in cardiovascular diseases, obesity and cancer.\" 1 (2018)","DOI":"10.3389\/fphys.2018.00557"},{"key":"38","doi-asserted-by":"crossref","unstructured":"JC Zhong, ZZ Zhang, W Wang, et al.  \"Biochim Biophys Acta Mol Basis Dis.\"  1863, \"Targeting the apelin pathway as a novel therapeutic approach for cardiovascular diseases.\" 1942 (2017)","DOI":"10.1016\/j.bbadis.2016.11.007"},{"key":"39","doi-asserted-by":"crossref","unstructured":"HB Kwon, S Wang, CSM Helker, et al.  \"Nat Commun.\"  7, \"In vivo modulation of endothelial polarization by Apelin receptor signalling.\" 11805 (2016)","DOI":"10.1038\/ncomms11805"},{"key":"40","doi-asserted-by":"crossref","unstructured":"M Boerma, JJCM Kruse, MM Van Loenen, et al.  \"Strahlenther Onkol.\"  180, \"Increased deposition of von Willebrand factor in the rat heart after local ionizing irradiation.\" 109 (2004)","DOI":"10.1007\/s00066-004-1138-0"},{"key":"42","doi-asserted-by":"crossref","unstructured":"D Kenchegowda, B Legesse, B Hritzo, et al.  \"Radiat Res.\"  190, \"Selective insulin-like growth factor resistance associated with heart hemorrhages and poor prognosis in a novel preclinical model of the hematopoietic acute radiation syndrome.\" 164 (2018)","DOI":"10.1667\/RR14993.1"},{"key":"43","doi-asserted-by":"crossref","unstructured":"B Legesse, A Kaur, D Kenchegowda, et al.  \"Int J Radiat Oncol Biol Phys.\"  103, \"Neulasta regimen for the hematopoietic acute radiation syndrome: Effects beyond neutrophil recovery.\" 935 (2019)","DOI":"10.1016\/j.ijrobp.2018.11.043"},{"key":"44","doi-asserted-by":"crossref","unstructured":"S Gencer, EPC Van Der Vorst, M Aslani, et al.  \"Thromb Haemost.\"  119, \"Atypical chemokine receptors in 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enable pig genetics and genomics research.\" giaa051 (2020)","DOI":"10.1093\/gigascience\/giaa051"},{"key":"50","unstructured":"et al.  \"Ensembl genome browser 99;.\"  , \"Pig assembly and gene annotation.\"  (2020)"},{"key":"51","doi-asserted-by":"crossref","unstructured":"C Zhao, Y Lv, Y Duan, et al.  \"Adv Exp Med Biol.\"  1229, \"Circulating non-coding RNAs and cardiovascular diseases.\" 357 (2020)","DOI":"10.1007\/978-981-15-1671-9_22"},{"key":"52","doi-asserted-by":"crossref","unstructured":"J Viereck  and T Thum  \"Circ Res.\"  120, \"Circulating noncoding RNAs as biomarkers of cardiovascular disease and injury.\" 381 (2017)","DOI":"10.1161\/CIRCRESAHA.116.308434"}],"container-title":["Radiation Research"],"original-title":[],"deposited":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T10:46:43Z","timestamp":1793443603000},"score":1,"resource":{"primary":{"URL":"https:\/\/bioone.org\/journals\/radiation-research\/volume-194\/issue-4\/RADE-20-00123.1\/Gene-Expression-Profiles-from-Heart-Lung-and-Liver-Samples-of\/10.1667\/RADE-20-00123.1.full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,9,16]]},"references-count":52,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2020,10,1]]}},"URL":"https:\/\/doi.org\/10.1667\/rade-20-00123.1","relation":{},"ISSN":["0033-7587","1938-5404"],"issn-type":[{"value":"0033-7587","type":"print"},{"value":"1938-5404","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,9,16]]}}}