Induction of oxidative stress biomarkers following whole-body irradiation in mice
Dose assessment is an important issue for radiation emergency medicine to determine appropriate clinical treatment. Hematopoietic tissues are extremely vulnerable to radiation exposure. A decrease in blood cell count following radiation exposure is the first quantitative bio-indicator using hematolo...
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| description | Dose assessment is an important issue for radiation emergency medicine to determine appropriate clinical treatment. Hematopoietic tissues are extremely vulnerable to radiation exposure. A decrease in blood cell count following radiation exposure is the first quantitative bio-indicator using hematological techniques. We further examined induction of oxidative stress biomarkers in residual lymphocytes to identify new biomarkers for dosimetry. In vivo whole-body radiation to mice exposed to 5 Gy significantly induces DNA double-strand breaks, which were visualized by γ-H2AX in mouse blood cells. Mouse blood smears and peripheral blood mononuclear cells (PBMC) isolated from irradiated mice were used for immunostaining for oxidative biomarkers, parkin or Nrf2. Parkin is the E3 ubiquitin ligase, which is normally localized in the cytoplasm, is relocated to abnormal mitochondria with low membrane potential (ΔΨm), where it promotes clearance via mitophagy. Nrf2 transcription factor controls the major cellular antioxidant responses. Both markers of oxidative stress were more sensitive and persistent over time than nuclear DNA damage. In conclusion, parkin and Nrf2 are potential biomarkers for use in radiation dosimetry. Identification of several biological markers which show different kinetics for radiation response is essential for radiation dosimetry that allows the assessment of radiation injury and efficacy of clinical treatment in emergency radiation incidents. Radiation-induced oxidative damage is useful not only for radiation dose assessment but also for evaluation of radiation risks on humans. |
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Hematopoietic tissues are extremely vulnerable to radiation exposure. A decrease in blood cell count following radiation exposure is the first quantitative bio-indicator using hematological techniques. We further examined induction of oxidative stress biomarkers in residual lymphocytes to identify new biomarkers for dosimetry. In vivo whole-body radiation to mice exposed to 5 Gy significantly induces DNA double-strand breaks, which were visualized by γ-H2AX in mouse blood cells. Mouse blood smears and peripheral blood mononuclear cells (PBMC) isolated from irradiated mice were used for immunostaining for oxidative biomarkers, parkin or Nrf2. Parkin is the E3 ubiquitin ligase, which is normally localized in the cytoplasm, is relocated to abnormal mitochondria with low membrane potential (ΔΨm), where it promotes clearance via mitophagy. Nrf2 transcription factor controls the major cellular antioxidant responses. Both markers of oxidative stress were more sensitive and persistent over time than nuclear DNA damage. In conclusion, parkin and Nrf2 are potential biomarkers for use in radiation dosimetry. Identification of several biological markers which show different kinetics for radiation response is essential for radiation dosimetry that allows the assessment of radiation injury and efficacy of clinical treatment in emergency radiation incidents. Radiation-induced oxidative damage is useful not only for radiation dose assessment but also for evaluation of radiation risks on humans.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0240108</identifier><identifier>PMID: 33002096</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Animals ; Antioxidants ; Bioindicators ; Biological markers ; Biology and Life Sciences ; Biomarkers ; Biomarkers - analysis ; Blood ; Blood cells ; Cytoplasm ; Deoxyribonucleic acid ; DNA ; DNA Breaks, Double-Stranded - radiation effects ; DNA damage ; Dosimeters ; Dosimetry ; Emergency medical care ; Emergency medical services ; Environmental health ; Experiments ; Exposure ; Health aspects ; Hematology ; Indicator species ; Irradiation ; Laboratories ; Leukocytes (mononuclear) ; Leukocytes, Mononuclear - pathology ; Leukocytes, Mononuclear - radiation effects ; Lymphocytes ; Male ; Medical research ; Medicine and Health Sciences ; Membrane potential ; Methods ; Mice ; Mice, Inbred C57BL ; Mitochondria ; NF-E2-Related Factor 2 - analysis ; Nuclear accidents & safety ; Oxidative stress ; Oxidative Stress - radiation effects ; Peripheral blood mononuclear cells ; Physical Sciences ; Public health ; Radiation ; Radiation damage ; Radiation dosage ; Radiation dosimetry ; Radiation effects ; Radiation exposure ; Radiation injuries ; Radiation therapy ; Research and Analysis Methods ; Ubiquitin ; Ubiquitin-protein ligase ; Ubiquitin-Protein Ligases - analysis ; Whole-Body Irradiation - adverse effects</subject><ispartof>PloS one, 2020-10, Vol.15 (10), p.e0240108</ispartof><rights>COPYRIGHT 2020 Public Library of Science</rights><rights>2020 Shimura 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>2020 Shimura et al 2020 Shimura et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c736t-3f6d9fecc736b35f4cbc5601f6167d9ba7133250f6421ae719c40f9022b0dd293</citedby><cites>FETCH-LOGICAL-c736t-3f6d9fecc736b35f4cbc5601f6167d9ba7133250f6421ae719c40f9022b0dd293</cites><orcidid>0000-0002-2418-2991</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/PMC7529313/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7529313/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,2102,2928,23866,27924,27925,53791,53793,79600,79601</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33002096$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Hamada, Nobuyuki</contributor><creatorcontrib>Shimura, Tsutomu</creatorcontrib><creatorcontrib>Nakashiro, Chinami</creatorcontrib><creatorcontrib>Narao, Momoka</creatorcontrib><creatorcontrib>Ushiyama, Akira</creatorcontrib><title>Induction of oxidative stress biomarkers following whole-body irradiation in mice</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Dose assessment is an important issue for radiation emergency medicine to determine appropriate clinical treatment. Hematopoietic tissues are extremely vulnerable to radiation exposure. A decrease in blood cell count following radiation exposure is the first quantitative bio-indicator using hematological techniques. We further examined induction of oxidative stress biomarkers in residual lymphocytes to identify new biomarkers for dosimetry. In vivo whole-body radiation to mice exposed to 5 Gy significantly induces DNA double-strand breaks, which were visualized by γ-H2AX in mouse blood cells. Mouse blood smears and peripheral blood mononuclear cells (PBMC) isolated from irradiated mice were used for immunostaining for oxidative biomarkers, parkin or Nrf2. Parkin is the E3 ubiquitin ligase, which is normally localized in the cytoplasm, is relocated to abnormal mitochondria with low membrane potential (ΔΨm), where it promotes clearance via mitophagy. Nrf2 transcription factor controls the major cellular antioxidant responses. Both markers of oxidative stress were more sensitive and persistent over time than nuclear DNA damage. In conclusion, parkin and Nrf2 are potential biomarkers for use in radiation dosimetry. Identification of several biological markers which show different kinetics for radiation response is essential for radiation dosimetry that allows the assessment of radiation injury and efficacy of clinical treatment in emergency radiation incidents. Radiation-induced oxidative damage is useful not only for radiation dose assessment but also for evaluation of radiation risks on humans.</description><subject>Animals</subject><subject>Antioxidants</subject><subject>Bioindicators</subject><subject>Biological markers</subject><subject>Biology and Life Sciences</subject><subject>Biomarkers</subject><subject>Biomarkers - analysis</subject><subject>Blood</subject><subject>Blood cells</subject><subject>Cytoplasm</subject><subject>Deoxyribonucleic acid</subject><subject>DNA</subject><subject>DNA Breaks, Double-Stranded - radiation effects</subject><subject>DNA damage</subject><subject>Dosimeters</subject><subject>Dosimetry</subject><subject>Emergency medical care</subject><subject>Emergency medical services</subject><subject>Environmental health</subject><subject>Experiments</subject><subject>Exposure</subject><subject>Health aspects</subject><subject>Hematology</subject><subject>Indicator species</subject><subject>Irradiation</subject><subject>Laboratories</subject><subject>Leukocytes (mononuclear)</subject><subject>Leukocytes, Mononuclear - 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Hematopoietic tissues are extremely vulnerable to radiation exposure. A decrease in blood cell count following radiation exposure is the first quantitative bio-indicator using hematological techniques. We further examined induction of oxidative stress biomarkers in residual lymphocytes to identify new biomarkers for dosimetry. In vivo whole-body radiation to mice exposed to 5 Gy significantly induces DNA double-strand breaks, which were visualized by γ-H2AX in mouse blood cells. Mouse blood smears and peripheral blood mononuclear cells (PBMC) isolated from irradiated mice were used for immunostaining for oxidative biomarkers, parkin or Nrf2. Parkin is the E3 ubiquitin ligase, which is normally localized in the cytoplasm, is relocated to abnormal mitochondria with low membrane potential (ΔΨm), where it promotes clearance via mitophagy. Nrf2 transcription factor controls the major cellular antioxidant responses. Both markers of oxidative stress were more sensitive and persistent over time than nuclear DNA damage. In conclusion, parkin and Nrf2 are potential biomarkers for use in radiation dosimetry. Identification of several biological markers which show different kinetics for radiation response is essential for radiation dosimetry that allows the assessment of radiation injury and efficacy of clinical treatment in emergency radiation incidents. Radiation-induced oxidative damage is useful not only for radiation dose assessment but also for evaluation of radiation risks on humans.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>33002096</pmid><doi>10.1371/journal.pone.0240108</doi><tpages>e0240108</tpages><orcidid>https://orcid.org/0000-0002-2418-2991</orcidid><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Public Library of Science (PLoS) Journals Open Access; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Animals Antioxidants Bioindicators Biological markers Biology and Life Sciences Biomarkers Biomarkers - analysis Blood Blood cells Cytoplasm Deoxyribonucleic acid DNA DNA Breaks, Double-Stranded - radiation effects DNA damage Dosimeters Dosimetry Emergency medical care Emergency medical services Environmental health Experiments Exposure Health aspects Hematology Indicator species Irradiation Laboratories Leukocytes (mononuclear) Leukocytes, Mononuclear - pathology Leukocytes, Mononuclear - radiation effects Lymphocytes Male Medical research Medicine and Health Sciences Membrane potential Methods Mice Mice, Inbred C57BL Mitochondria NF-E2-Related Factor 2 - analysis Nuclear accidents & safety Oxidative stress Oxidative Stress - radiation effects Peripheral blood mononuclear cells Physical Sciences Public health Radiation Radiation damage Radiation dosage Radiation dosimetry Radiation effects Radiation exposure Radiation injuries Radiation therapy Research and Analysis Methods Ubiquitin Ubiquitin-protein ligase Ubiquitin-Protein Ligases - analysis Whole-Body Irradiation - adverse effects |
| title | Induction of oxidative stress biomarkers following whole-body irradiation in mice |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-25T23%3A36%3A26IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Induction%20of%20oxidative%20stress%20biomarkers%20following%20whole-body%20irradiation%20in%20mice&rft.jtitle=PloS%20one&rft.au=Shimura,%20Tsutomu&rft.date=2020-10-01&rft.volume=15&rft.issue=10&rft.spage=e0240108&rft.pages=e0240108-&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0240108&rft_dat=%3Cgale_plos_%3EA637120980%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2447830196&rft_id=info:pmid/33002096&rft_galeid=A637120980&rft_doaj_id=oai_doaj_org_article_8c4c4569f2f94b2a88462f5fde139603&rfr_iscdi=true |