Delayed effects of acute whole body lethal radiation exposure in mice pre-treated with BBT-059
The threat of nuclear exposure is heightened and it is imperative to identify potential countermeasures for acute radiation syndrome. Currently no countermeasures have been approved for prophylactic administration. Effective countermeasures should function to increase survival in the short term as w...
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| creator | Sharma, Neel K. Holmes-Hampton, Gregory P. Kumar, Vidya P. Biswas, Shukla Wuddie, Kefale Stone, Sasha Aschenake, Zemenu Wilkins, William L. Fam, Christine M. Cox, George N. Ghosh, Sanchita P. |
| description | The threat of nuclear exposure is heightened and it is imperative to identify potential countermeasures for acute radiation syndrome. Currently no countermeasures have been approved for prophylactic administration. Effective countermeasures should function to increase survival in the short term as well as to increase the overall prognosis of an exposed individual long term. Here we describe the use of a promising radiation countermeasure, BBT-059, and the results of a long term mouse study (up to 12 months) in the male CD2F1 strain using
60
Co gamma irradiation (~0.6 Gy/min, 7.5–12.5 Gy). We report the dose reduction factor of 1.28 for BBT-059 (0.3 mg/kg) compared to control administered 24 h prior to irradiation. In the long term study animals showed accelerated recovery in peripheral blood cell counts, bone marrow colony forming units, sternal cellularity and megakaryocyte numbers in drug treated mice compared to formulation buffer. In addition, increased senescence was observed in the kidneys of animals administered control or drug and exposed to the highest doses of radiation. Decreased levels of E-cadherin, LaminB1 and increased levels of Cyc-D and p21 in spleen lysates were observed in animals administered control. Taken together the results indicate a high level of protection following BBT-059 administration in mice exposed to lethal and supralethal doses of total body gamma-radiation. |
| doi_str_mv | 10.1038/s41598-020-63818-7 |
| format | Article |
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60
Co gamma irradiation (~0.6 Gy/min, 7.5–12.5 Gy). We report the dose reduction factor of 1.28 for BBT-059 (0.3 mg/kg) compared to control administered 24 h prior to irradiation. In the long term study animals showed accelerated recovery in peripheral blood cell counts, bone marrow colony forming units, sternal cellularity and megakaryocyte numbers in drug treated mice compared to formulation buffer. In addition, increased senescence was observed in the kidneys of animals administered control or drug and exposed to the highest doses of radiation. Decreased levels of E-cadherin, LaminB1 and increased levels of Cyc-D and p21 in spleen lysates were observed in animals administered control. Taken together the results indicate a high level of protection following BBT-059 administration in mice exposed to lethal and supralethal doses of total body gamma-radiation.</description><identifier>ISSN: 2045-2322</identifier><identifier>EISSN: 2045-2322</identifier><identifier>DOI: 10.1038/s41598-020-63818-7</identifier><identifier>PMID: 32321983</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>13/51 ; 14/19 ; 631/136/7 ; 64/60 ; 692/53/2423 ; Alkaline Phosphatase - blood ; Animals ; Aspartate Aminotransferases - blood ; Blood Cell Count ; Bone marrow ; Cadherins - metabolism ; Clone Cells ; Colony-Forming Units Assay ; Dose-Response Relationship, Radiation ; Drug dosages ; E-cadherin ; Gamma Rays ; Hematopoietic Stem Cells - metabolism ; Hematopoietic Stem Cells - radiation effects ; Humanities and Social Sciences ; Interleukin-11 - pharmacology ; Irradiation ; Kidney - pathology ; Kidney - radiation effects ; Kidneys ; Liver - pathology ; Liver - radiation effects ; Long term ; Lysates ; Male ; Medical prognosis ; Mice ; multidisciplinary ; Multidisciplinary Sciences ; Organ Specificity - radiation effects ; Peripheral blood ; Radiation Exposure ; Science ; Science & Technology ; Science & Technology - Other Topics ; Science (multidisciplinary) ; Senescence ; Spleen ; Survival Analysis ; Whole-Body Irradiation</subject><ispartof>Scientific reports, 2020-04, Vol.10 (1), p.6825, Article 6825</ispartof><rights>The Author(s) 2020</rights><rights>The Author(s) 2020. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>true</woscitedreferencessubscribed><woscitedreferencescount>16</woscitedreferencescount><woscitedreferencesoriginalsourcerecordid>wos000560324300033</woscitedreferencesoriginalsourcerecordid><citedby>FETCH-LOGICAL-c513t-c73998d4789c0d8f6e2a5f484318aae7a2b5533e17727f21f0ae5f8fb504342f3</citedby><cites>FETCH-LOGICAL-c513t-c73998d4789c0d8f6e2a5f484318aae7a2b5533e17727f21f0ae5f8fb504342f3</cites><orcidid>0000-0001-6808-5010 ; 0000-0002-0261-460X</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7176697/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7176697/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,315,729,782,786,866,887,2118,27933,27934,28257,41129,42198,51585,53800,53802</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32321983$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Sharma, Neel K.</creatorcontrib><creatorcontrib>Holmes-Hampton, Gregory P.</creatorcontrib><creatorcontrib>Kumar, Vidya P.</creatorcontrib><creatorcontrib>Biswas, Shukla</creatorcontrib><creatorcontrib>Wuddie, Kefale</creatorcontrib><creatorcontrib>Stone, Sasha</creatorcontrib><creatorcontrib>Aschenake, Zemenu</creatorcontrib><creatorcontrib>Wilkins, William L.</creatorcontrib><creatorcontrib>Fam, Christine M.</creatorcontrib><creatorcontrib>Cox, George N.</creatorcontrib><creatorcontrib>Ghosh, Sanchita P.</creatorcontrib><title>Delayed effects of acute whole body lethal radiation exposure in mice pre-treated with BBT-059</title><title>Scientific reports</title><addtitle>Sci Rep</addtitle><addtitle>SCI REP-UK</addtitle><addtitle>Sci Rep</addtitle><description>The threat of nuclear exposure is heightened and it is imperative to identify potential countermeasures for acute radiation syndrome. Currently no countermeasures have been approved for prophylactic administration. Effective countermeasures should function to increase survival in the short term as well as to increase the overall prognosis of an exposed individual long term. Here we describe the use of a promising radiation countermeasure, BBT-059, and the results of a long term mouse study (up to 12 months) in the male CD2F1 strain using
60
Co gamma irradiation (~0.6 Gy/min, 7.5–12.5 Gy). We report the dose reduction factor of 1.28 for BBT-059 (0.3 mg/kg) compared to control administered 24 h prior to irradiation. In the long term study animals showed accelerated recovery in peripheral blood cell counts, bone marrow colony forming units, sternal cellularity and megakaryocyte numbers in drug treated mice compared to formulation buffer. In addition, increased senescence was observed in the kidneys of animals administered control or drug and exposed to the highest doses of radiation. Decreased levels of E-cadherin, LaminB1 and increased levels of Cyc-D and p21 in spleen lysates were observed in animals administered control. Taken together the results indicate a high level of protection following BBT-059 administration in mice exposed to lethal and supralethal doses of total body gamma-radiation.</description><subject>13/51</subject><subject>14/19</subject><subject>631/136/7</subject><subject>64/60</subject><subject>692/53/2423</subject><subject>Alkaline Phosphatase - blood</subject><subject>Animals</subject><subject>Aspartate Aminotransferases - blood</subject><subject>Blood Cell Count</subject><subject>Bone marrow</subject><subject>Cadherins - metabolism</subject><subject>Clone Cells</subject><subject>Colony-Forming Units Assay</subject><subject>Dose-Response Relationship, Radiation</subject><subject>Drug dosages</subject><subject>E-cadherin</subject><subject>Gamma Rays</subject><subject>Hematopoietic Stem Cells - metabolism</subject><subject>Hematopoietic Stem Cells - radiation effects</subject><subject>Humanities and Social Sciences</subject><subject>Interleukin-11 - pharmacology</subject><subject>Irradiation</subject><subject>Kidney - 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Other Topics</topic><topic>Science (multidisciplinary)</topic><topic>Senescence</topic><topic>Spleen</topic><topic>Survival Analysis</topic><topic>Whole-Body Irradiation</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Sharma, Neel K.</creatorcontrib><creatorcontrib>Holmes-Hampton, Gregory P.</creatorcontrib><creatorcontrib>Kumar, Vidya P.</creatorcontrib><creatorcontrib>Biswas, Shukla</creatorcontrib><creatorcontrib>Wuddie, Kefale</creatorcontrib><creatorcontrib>Stone, Sasha</creatorcontrib><creatorcontrib>Aschenake, Zemenu</creatorcontrib><creatorcontrib>Wilkins, William L.</creatorcontrib><creatorcontrib>Fam, Christine M.</creatorcontrib><creatorcontrib>Cox, George N.</creatorcontrib><creatorcontrib>Ghosh, Sanchita P.</creatorcontrib><collection>Springer Nature OA/Free Journals</collection><collection>Web of Science - Science Citation Index Expanded - 2020</collection><collection>Web of Science Core Collection</collection><collection>Science Citation Index Expanded</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Science Database (Alumni Edition)</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Science Database</collection><collection>Biological Science Database</collection><collection>Access via ProQuest (Open Access)</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central Basic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Scientific reports</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Sharma, Neel K.</au><au>Holmes-Hampton, Gregory P.</au><au>Kumar, Vidya P.</au><au>Biswas, Shukla</au><au>Wuddie, Kefale</au><au>Stone, Sasha</au><au>Aschenake, Zemenu</au><au>Wilkins, William L.</au><au>Fam, Christine M.</au><au>Cox, George N.</au><au>Ghosh, Sanchita P.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Delayed effects of acute whole body lethal radiation exposure in mice pre-treated with BBT-059</atitle><jtitle>Scientific reports</jtitle><stitle>Sci Rep</stitle><stitle>SCI REP-UK</stitle><addtitle>Sci Rep</addtitle><date>2020-04-22</date><risdate>2020</risdate><volume>10</volume><issue>1</issue><spage>6825</spage><pages>6825-</pages><artnum>6825</artnum><issn>2045-2322</issn><eissn>2045-2322</eissn><abstract>The threat of nuclear exposure is heightened and it is imperative to identify potential countermeasures for acute radiation syndrome. Currently no countermeasures have been approved for prophylactic administration. Effective countermeasures should function to increase survival in the short term as well as to increase the overall prognosis of an exposed individual long term. Here we describe the use of a promising radiation countermeasure, BBT-059, and the results of a long term mouse study (up to 12 months) in the male CD2F1 strain using
60
Co gamma irradiation (~0.6 Gy/min, 7.5–12.5 Gy). We report the dose reduction factor of 1.28 for BBT-059 (0.3 mg/kg) compared to control administered 24 h prior to irradiation. In the long term study animals showed accelerated recovery in peripheral blood cell counts, bone marrow colony forming units, sternal cellularity and megakaryocyte numbers in drug treated mice compared to formulation buffer. In addition, increased senescence was observed in the kidneys of animals administered control or drug and exposed to the highest doses of radiation. Decreased levels of E-cadherin, LaminB1 and increased levels of Cyc-D and p21 in spleen lysates were observed in animals administered control. Taken together the results indicate a high level of protection following BBT-059 administration in mice exposed to lethal and supralethal doses of total body gamma-radiation.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>32321983</pmid><doi>10.1038/s41598-020-63818-7</doi><tpages>13</tpages><orcidid>https://orcid.org/0000-0001-6808-5010</orcidid><orcidid>https://orcid.org/0000-0002-0261-460X</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | 13/51 14/19 631/136/7 64/60 692/53/2423 Alkaline Phosphatase - blood Animals Aspartate Aminotransferases - blood Blood Cell Count Bone marrow Cadherins - metabolism Clone Cells Colony-Forming Units Assay Dose-Response Relationship, Radiation Drug dosages E-cadherin Gamma Rays Hematopoietic Stem Cells - metabolism Hematopoietic Stem Cells - radiation effects Humanities and Social Sciences Interleukin-11 - pharmacology Irradiation Kidney - pathology Kidney - radiation effects Kidneys Liver - pathology Liver - radiation effects Long term Lysates Male Medical prognosis Mice multidisciplinary Multidisciplinary Sciences Organ Specificity - radiation effects Peripheral blood Radiation Exposure Science Science & Technology Science & Technology - Other Topics Science (multidisciplinary) Senescence Spleen Survival Analysis Whole-Body Irradiation |
| title | Delayed effects of acute whole body lethal radiation exposure in mice pre-treated with BBT-059 |
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