γ-H2AX Kinetic Profile in Mouse Lymphocytes Exposed to the Internal Emitters Cesium-137 and Strontium-90
In the event of a dirty bomb scenario or an industrial nuclear accident, a significant dose of volatile radionuclides such as 137Cs and 90Sr may be dispersed into the atmosphere as a component of fallout and inhaled or ingested by hundreds and thousands of people. To study the effects of prolonged e...
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| creator | Turner, Helen C Shuryak, Igor Weber, Waylon Doyle-Eisele, Melanie Melo, Dunstana Guilmette, Raymond Amundson, Sally A Brenner, David J |
| description | In the event of a dirty bomb scenario or an industrial nuclear accident, a significant dose of volatile radionuclides such as 137Cs and 90Sr may be dispersed into the atmosphere as a component of fallout and inhaled or ingested by hundreds and thousands of people. To study the effects of prolonged exposure to ingested radionuclides, we have performed long-term (30 day) internal-emitter mouse irradiations using soluble-injected 137CsCl and 90SrCl2 radioisotopes. The effect of ionizing radiation on the induction and repair of DNA double strand breaks (DSBs) in peripheral mouse lymphocytes in vivo was determined using the γ-H2AX biodosimetry marker. Using a serial sacrifice experimental design, whole-body radiation absorbed doses for 137Cs (0 to 10 Gy) and 90Sr (0 to 49 Gy) were delivered over 30 days following exposure to each radionuclide. The committed absorbed doses of the two internal emitters as a function of time post exposure were calculated based on their retention parameters and their derived dose coefficients for each specific sacrifice time. In order to measure the kinetic profile for γ-H2AX, peripheral blood samples were drawn at 5 specific timed dose points over the 30-day study period and the total γ-H2AX nuclear fluorescence per lymphocyte was determined using image analysis software. A key finding was that a significant γ-H2AX signal was observed in vivo several weeks after a single radionuclide exposure. A mechanistically-motivated model was used to analyze the temporal kinetics of γ-H2AX fluorescence. Exposure to either radionuclide showed two peaks of γ-H2AX: one within the first week, which may represent the death of mature, differentiated lymphocytes, and the second at approximately three weeks, which may represent the production of new lymphocytes from damaged progenitor cells. The complexity of the observed responses to internal irradiation is likely caused by the interplay between continual production and repair of DNA damage, cell cycle effects and apoptosis. |
| doi_str_mv | 10.1371/journal.pone.0143815 |
| format | Article |
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To study the effects of prolonged exposure to ingested radionuclides, we have performed long-term (30 day) internal-emitter mouse irradiations using soluble-injected 137CsCl and 90SrCl2 radioisotopes. The effect of ionizing radiation on the induction and repair of DNA double strand breaks (DSBs) in peripheral mouse lymphocytes in vivo was determined using the γ-H2AX biodosimetry marker. Using a serial sacrifice experimental design, whole-body radiation absorbed doses for 137Cs (0 to 10 Gy) and 90Sr (0 to 49 Gy) were delivered over 30 days following exposure to each radionuclide. The committed absorbed doses of the two internal emitters as a function of time post exposure were calculated based on their retention parameters and their derived dose coefficients for each specific sacrifice time. In order to measure the kinetic profile for γ-H2AX, peripheral blood samples were drawn at 5 specific timed dose points over the 30-day study period and the total γ-H2AX nuclear fluorescence per lymphocyte was determined using image analysis software. A key finding was that a significant γ-H2AX signal was observed in vivo several weeks after a single radionuclide exposure. A mechanistically-motivated model was used to analyze the temporal kinetics of γ-H2AX fluorescence. Exposure to either radionuclide showed two peaks of γ-H2AX: one within the first week, which may represent the death of mature, differentiated lymphocytes, and the second at approximately three weeks, which may represent the production of new lymphocytes from damaged progenitor cells. The complexity of the observed responses to internal irradiation is likely caused by the interplay between continual production and repair of DNA damage, cell cycle effects and apoptosis.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0143815</identifier><identifier>PMID: 26618801</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Animals ; Apoptosis ; Blood ; Cancer ; Cell cycle ; Cell Cycle - radiation effects ; Cells (biology) ; Cesium ; Cesium 137 ; Cesium isotopes ; Cesium radioisotopes ; Cesium Radioisotopes - toxicity ; Deoxyribonucleic acid ; DNA ; DNA Breaks, Double-Stranded ; DNA damage ; DNA repair ; DNA Repair - radiation effects ; Dose-Response Relationship, Radiation ; Emitters ; Experimental design ; Exposure ; Fallout ; Fluorescence ; Histones - blood ; Image analysis ; Image processing ; In vivo methods and tests ; Ionizing radiation ; Irradiation ; Kinetics ; Leukemia ; Lymphocytes ; Lymphocytes - cytology ; Lymphocytes - radiation effects ; Mathematical functions ; Medical research ; Mice ; Nuclear accidents ; Nuclear accidents & safety ; Nuclear fission ; Nuclear weapons ; Peripheral blood ; Phosphorylation ; Physical properties ; Progenitor cells ; Radiation ; Radiation damage ; Radioisotopes ; Repair ; Stem cells ; Strontium ; Strontium 90 ; Strontium radioisotopes ; Strontium Radioisotopes - toxicity ; Whole-Body Irradiation</subject><ispartof>PloS one, 2015-11, Vol.10 (11), p.e0143815-e0143815</ispartof><rights>2015 Turner et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2015 Turner et al 2015 Turner et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c526t-29f6801b4fb319f489ae7017455e4d44019f801d29c02ab74a693f2911196f433</citedby><cites>FETCH-LOGICAL-c526t-29f6801b4fb319f489ae7017455e4d44019f801d29c02ab74a693f2911196f433</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4664397/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4664397/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,2101,2927,23865,27923,27924,53790,53792,79471,79472</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26618801$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Price, Brendan D</contributor><creatorcontrib>Turner, Helen C</creatorcontrib><creatorcontrib>Shuryak, Igor</creatorcontrib><creatorcontrib>Weber, Waylon</creatorcontrib><creatorcontrib>Doyle-Eisele, Melanie</creatorcontrib><creatorcontrib>Melo, Dunstana</creatorcontrib><creatorcontrib>Guilmette, Raymond</creatorcontrib><creatorcontrib>Amundson, Sally A</creatorcontrib><creatorcontrib>Brenner, David J</creatorcontrib><title>γ-H2AX Kinetic Profile in Mouse Lymphocytes Exposed to the Internal Emitters Cesium-137 and Strontium-90</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>In the event of a dirty bomb scenario or an industrial nuclear accident, a significant dose of volatile radionuclides such as 137Cs and 90Sr may be dispersed into the atmosphere as a component of fallout and inhaled or ingested by hundreds and thousands of people. 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In order to measure the kinetic profile for γ-H2AX, peripheral blood samples were drawn at 5 specific timed dose points over the 30-day study period and the total γ-H2AX nuclear fluorescence per lymphocyte was determined using image analysis software. A key finding was that a significant γ-H2AX signal was observed in vivo several weeks after a single radionuclide exposure. A mechanistically-motivated model was used to analyze the temporal kinetics of γ-H2AX fluorescence. Exposure to either radionuclide showed two peaks of γ-H2AX: one within the first week, which may represent the death of mature, differentiated lymphocytes, and the second at approximately three weeks, which may represent the production of new lymphocytes from damaged progenitor cells. The complexity of the observed responses to internal irradiation is likely caused by the interplay between continual production and repair of DNA damage, cell cycle effects and apoptosis.</description><subject>Animals</subject><subject>Apoptosis</subject><subject>Blood</subject><subject>Cancer</subject><subject>Cell cycle</subject><subject>Cell Cycle - radiation effects</subject><subject>Cells (biology)</subject><subject>Cesium</subject><subject>Cesium 137</subject><subject>Cesium isotopes</subject><subject>Cesium radioisotopes</subject><subject>Cesium Radioisotopes - toxicity</subject><subject>Deoxyribonucleic acid</subject><subject>DNA</subject><subject>DNA Breaks, Double-Stranded</subject><subject>DNA damage</subject><subject>DNA repair</subject><subject>DNA Repair - radiation effects</subject><subject>Dose-Response Relationship, Radiation</subject><subject>Emitters</subject><subject>Experimental design</subject><subject>Exposure</subject><subject>Fallout</subject><subject>Fluorescence</subject><subject>Histones - blood</subject><subject>Image analysis</subject><subject>Image processing</subject><subject>In vivo methods and tests</subject><subject>Ionizing radiation</subject><subject>Irradiation</subject><subject>Kinetics</subject><subject>Leukemia</subject><subject>Lymphocytes</subject><subject>Lymphocytes - cytology</subject><subject>Lymphocytes - radiation effects</subject><subject>Mathematical functions</subject><subject>Medical research</subject><subject>Mice</subject><subject>Nuclear accidents</subject><subject>Nuclear accidents & safety</subject><subject>Nuclear fission</subject><subject>Nuclear weapons</subject><subject>Peripheral blood</subject><subject>Phosphorylation</subject><subject>Physical properties</subject><subject>Progenitor cells</subject><subject>Radiation</subject><subject>Radiation damage</subject><subject>Radioisotopes</subject><subject>Repair</subject><subject>Stem cells</subject><subject>Strontium</subject><subject>Strontium 90</subject><subject>Strontium radioisotopes</subject><subject>Strontium Radioisotopes - 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To study the effects of prolonged exposure to ingested radionuclides, we have performed long-term (30 day) internal-emitter mouse irradiations using soluble-injected 137CsCl and 90SrCl2 radioisotopes. The effect of ionizing radiation on the induction and repair of DNA double strand breaks (DSBs) in peripheral mouse lymphocytes in vivo was determined using the γ-H2AX biodosimetry marker. Using a serial sacrifice experimental design, whole-body radiation absorbed doses for 137Cs (0 to 10 Gy) and 90Sr (0 to 49 Gy) were delivered over 30 days following exposure to each radionuclide. The committed absorbed doses of the two internal emitters as a function of time post exposure were calculated based on their retention parameters and their derived dose coefficients for each specific sacrifice time. In order to measure the kinetic profile for γ-H2AX, peripheral blood samples were drawn at 5 specific timed dose points over the 30-day study period and the total γ-H2AX nuclear fluorescence per lymphocyte was determined using image analysis software. A key finding was that a significant γ-H2AX signal was observed in vivo several weeks after a single radionuclide exposure. A mechanistically-motivated model was used to analyze the temporal kinetics of γ-H2AX fluorescence. Exposure to either radionuclide showed two peaks of γ-H2AX: one within the first week, which may represent the death of mature, differentiated lymphocytes, and the second at approximately three weeks, which may represent the production of new lymphocytes from damaged progenitor cells. The complexity of the observed responses to internal irradiation is likely caused by the interplay between continual production and repair of DNA damage, cell cycle effects and apoptosis.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>26618801</pmid><doi>10.1371/journal.pone.0143815</doi><oa>free_for_read</oa></addata></record> |
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| recordid | cdi_plos_journals_1738003222 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Public Library of Science (PLoS); EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Animals Apoptosis Blood Cancer Cell cycle Cell Cycle - radiation effects Cells (biology) Cesium Cesium 137 Cesium isotopes Cesium radioisotopes Cesium Radioisotopes - toxicity Deoxyribonucleic acid DNA DNA Breaks, Double-Stranded DNA damage DNA repair DNA Repair - radiation effects Dose-Response Relationship, Radiation Emitters Experimental design Exposure Fallout Fluorescence Histones - blood Image analysis Image processing In vivo methods and tests Ionizing radiation Irradiation Kinetics Leukemia Lymphocytes Lymphocytes - cytology Lymphocytes - radiation effects Mathematical functions Medical research Mice Nuclear accidents Nuclear accidents & safety Nuclear fission Nuclear weapons Peripheral blood Phosphorylation Physical properties Progenitor cells Radiation Radiation damage Radioisotopes Repair Stem cells Strontium Strontium 90 Strontium radioisotopes Strontium Radioisotopes - toxicity Whole-Body Irradiation |
| title | γ-H2AX Kinetic Profile in Mouse Lymphocytes Exposed to the Internal Emitters Cesium-137 and Strontium-90 |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-09T01%3A34%3A38IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=%CE%B3-H2AX%20Kinetic%20Profile%20in%20Mouse%20Lymphocytes%20Exposed%20to%20the%20Internal%20Emitters%20Cesium-137%20and%20Strontium-90&rft.jtitle=PloS%20one&rft.au=Turner,%20Helen%20C&rft.date=2015-11-30&rft.volume=10&rft.issue=11&rft.spage=e0143815&rft.epage=e0143815&rft.pages=e0143815-e0143815&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0143815&rft_dat=%3Cproquest_plos_%3E1738814431%3C/proquest_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1738003222&rft_id=info:pmid/26618801&rft_doaj_id=oai_doaj_org_article_48c746335f424aa1b16c7fa5fdf31fe7&rfr_iscdi=true |