Low Doses of Oxygen Ion Irradiation Cause Acute Damage to Hematopoietic Cells in Mice
One of the major health risks to astronauts is radiation on long-duration space missions. Space radiation from sun and galactic cosmic rays consists primarily of 85% protons, 14% helium nuclei and 1% high-energy high-charge (HZE) particles, such as oxygen (16O), carbon, silicon, and iron ions. HZE p...
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| creator | Chang, Jianhui Luo, Yi Wang, Yingying Pathak, Rupak Sridharan, Vijayalakshmi Jones, Tamako Mao, Xiao Wen Nelson, Gregory Boerma, Marjan Hauer-Jensen, Martin Zhou, Daohong Shao, Lijian |
| description | One of the major health risks to astronauts is radiation on long-duration space missions. Space radiation from sun and galactic cosmic rays consists primarily of 85% protons, 14% helium nuclei and 1% high-energy high-charge (HZE) particles, such as oxygen (16O), carbon, silicon, and iron ions. HZE particles exhibit dense linear tracks of ionization associated with clustered DNA damage and often high relative biological effectiveness (RBE). Therefore, new knowledge of risks from HZE particle exposures must be obtained. In the present study, we investigated the acute effects of low doses of 16O irradiation on the hematopoietic system. Specifically, we exposed C57BL/6J mice to 0.1, 0.25 and 1.0 Gy whole body 16O (600 MeV/n) irradiation and examined the effects on peripheral blood (PB) cells, and bone marrow (BM) hematopoietic stem cells (HSCs) and hematopoietic progenitor cells (HPCs) at two weeks after the exposure. The results showed that the numbers of white blood cells, lymphocytes, monocytes, neutrophils and platelets were significantly decreased in PB after exposure to 1.0 Gy, but not to 0.1 or 0.25 Gy. However, both the frequency and number of HPCs and HSCs were reduced in a radiation dose-dependent manner in comparison to un-irradiated controls. Furthermore, HPCs and HSCs from irradiated mice exhibited a significant reduction in clonogenic function determined by the colony-forming and cobblestone area-forming cell assays. These acute adverse effects of 16O irradiation on HSCs coincided with an increased production of reactive oxygen species (ROS), enhanced cell cycle entry of quiescent HSCs, and increased DNA damage. However, none of the 16O exposures induced apoptosis in HSCs. These data suggest that exposure to low doses of 16O irradiation induces acute BM injury in a dose-dependent manner primarily via increasing ROS production, cell cycling, and DNA damage in HSCs. This finding may aid in developing novel strategies in the protection of the hematopoietic system from space radiation. |
| doi_str_mv | 10.1371/journal.pone.0158097 |
| format | Article |
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Space radiation from sun and galactic cosmic rays consists primarily of 85% protons, 14% helium nuclei and 1% high-energy high-charge (HZE) particles, such as oxygen (16O), carbon, silicon, and iron ions. HZE particles exhibit dense linear tracks of ionization associated with clustered DNA damage and often high relative biological effectiveness (RBE). Therefore, new knowledge of risks from HZE particle exposures must be obtained. In the present study, we investigated the acute effects of low doses of 16O irradiation on the hematopoietic system. Specifically, we exposed C57BL/6J mice to 0.1, 0.25 and 1.0 Gy whole body 16O (600 MeV/n) irradiation and examined the effects on peripheral blood (PB) cells, and bone marrow (BM) hematopoietic stem cells (HSCs) and hematopoietic progenitor cells (HPCs) at two weeks after the exposure. The results showed that the numbers of white blood cells, lymphocytes, monocytes, neutrophils and platelets were significantly decreased in PB after exposure to 1.0 Gy, but not to 0.1 or 0.25 Gy. However, both the frequency and number of HPCs and HSCs were reduced in a radiation dose-dependent manner in comparison to un-irradiated controls. Furthermore, HPCs and HSCs from irradiated mice exhibited a significant reduction in clonogenic function determined by the colony-forming and cobblestone area-forming cell assays. These acute adverse effects of 16O irradiation on HSCs coincided with an increased production of reactive oxygen species (ROS), enhanced cell cycle entry of quiescent HSCs, and increased DNA damage. However, none of the 16O exposures induced apoptosis in HSCs. These data suggest that exposure to low doses of 16O irradiation induces acute BM injury in a dose-dependent manner primarily via increasing ROS production, cell cycling, and DNA damage in HSCs. This finding may aid in developing novel strategies in the protection of the hematopoietic system from space radiation.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0158097</identifier><identifier>PMID: 27367604</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Acute effects ; Analysis ; Animals ; Apoptosis ; Astronauts ; Biological effects ; Biology and life sciences ; Blood ; Blood Cell Count ; Blood cells ; Bone marrow ; Cell cycle ; Cell Cycle - radiation effects ; Cells (biology) ; Cosmic rays ; Deoxyribonucleic acid ; DNA ; DNA Damage ; DNA methylation ; Dose-Response Relationship, Radiation ; Drug dosages ; Energy charge ; Exposure ; Extraterrestrial radiation ; Forming ; Galactic cosmic rays ; Health aspects ; Health risks ; Helium ; Hematopoietic stem cells ; Hematopoietic Stem Cells - cytology ; Hematopoietic Stem Cells - metabolism ; Hematopoietic Stem Cells - radiation effects ; Hematopoietic system ; High energy astronomy ; Ion beams ; Ion irradiation ; Ionization ; Ionizing radiation ; Iron ; Irradiation ; Laboratories ; Leukocytes (neutrophilic) ; Lymphocytes ; Male ; Mice ; Mice, Inbred C57BL ; Monocytes ; Nuclei ; Nuclei (nuclear physics) ; Oxidative stress ; Oxidative Stress - radiation effects ; Oxygen ; Oxygen - adverse effects ; Peripheral blood ; Pharmaceutical sciences ; Physiological aspects ; Platelets ; Progenitor cells ; Protons ; Radiation ; Radiation damage ; Radiation dosage ; Reactive oxygen species ; Reactive Oxygen Species - metabolism ; Relative biological effectiveness (RBE) ; Research and Analysis Methods ; Rodents ; Space missions ; Stem cell transplantation ; Stem cells</subject><ispartof>PloS one, 2016-07, Vol.11 (7), p.e0158097-e0158097</ispartof><rights>COPYRIGHT 2016 Public Library of Science</rights><rights>2016 Chang 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>2016 Chang et al 2016 Chang et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c791t-f1f7823ac3c611de9e1eb3ed937648fb80f21892a07885fb8adb9f8ca857a17a3</citedby><cites>FETCH-LOGICAL-c791t-f1f7823ac3c611de9e1eb3ed937648fb80f21892a07885fb8adb9f8ca857a17a3</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/PMC4930193/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4930193/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79343,79344</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27367604$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Chang, Jianhui</creatorcontrib><creatorcontrib>Luo, Yi</creatorcontrib><creatorcontrib>Wang, Yingying</creatorcontrib><creatorcontrib>Pathak, Rupak</creatorcontrib><creatorcontrib>Sridharan, Vijayalakshmi</creatorcontrib><creatorcontrib>Jones, Tamako</creatorcontrib><creatorcontrib>Mao, Xiao Wen</creatorcontrib><creatorcontrib>Nelson, Gregory</creatorcontrib><creatorcontrib>Boerma, Marjan</creatorcontrib><creatorcontrib>Hauer-Jensen, Martin</creatorcontrib><creatorcontrib>Zhou, Daohong</creatorcontrib><creatorcontrib>Shao, Lijian</creatorcontrib><title>Low Doses of Oxygen Ion Irradiation Cause Acute Damage to Hematopoietic Cells in Mice</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>One of the major health risks to astronauts is radiation on long-duration space missions. Space radiation from sun and galactic cosmic rays consists primarily of 85% protons, 14% helium nuclei and 1% high-energy high-charge (HZE) particles, such as oxygen (16O), carbon, silicon, and iron ions. HZE particles exhibit dense linear tracks of ionization associated with clustered DNA damage and often high relative biological effectiveness (RBE). Therefore, new knowledge of risks from HZE particle exposures must be obtained. In the present study, we investigated the acute effects of low doses of 16O irradiation on the hematopoietic system. Specifically, we exposed C57BL/6J mice to 0.1, 0.25 and 1.0 Gy whole body 16O (600 MeV/n) irradiation and examined the effects on peripheral blood (PB) cells, and bone marrow (BM) hematopoietic stem cells (HSCs) and hematopoietic progenitor cells (HPCs) at two weeks after the exposure. The results showed that the numbers of white blood cells, lymphocytes, monocytes, neutrophils and platelets were significantly decreased in PB after exposure to 1.0 Gy, but not to 0.1 or 0.25 Gy. However, both the frequency and number of HPCs and HSCs were reduced in a radiation dose-dependent manner in comparison to un-irradiated controls. Furthermore, HPCs and HSCs from irradiated mice exhibited a significant reduction in clonogenic function determined by the colony-forming and cobblestone area-forming cell assays. These acute adverse effects of 16O irradiation on HSCs coincided with an increased production of reactive oxygen species (ROS), enhanced cell cycle entry of quiescent HSCs, and increased DNA damage. However, none of the 16O exposures induced apoptosis in HSCs. These data suggest that exposure to low doses of 16O irradiation induces acute BM injury in a dose-dependent manner primarily via increasing ROS production, cell cycling, and DNA damage in HSCs. This finding may aid in developing novel strategies in the protection of the hematopoietic system from space radiation.</description><subject>Acute effects</subject><subject>Analysis</subject><subject>Animals</subject><subject>Apoptosis</subject><subject>Astronauts</subject><subject>Biological effects</subject><subject>Biology and life sciences</subject><subject>Blood</subject><subject>Blood Cell Count</subject><subject>Blood cells</subject><subject>Bone marrow</subject><subject>Cell cycle</subject><subject>Cell Cycle - radiation effects</subject><subject>Cells (biology)</subject><subject>Cosmic rays</subject><subject>Deoxyribonucleic acid</subject><subject>DNA</subject><subject>DNA Damage</subject><subject>DNA methylation</subject><subject>Dose-Response Relationship, Radiation</subject><subject>Drug dosages</subject><subject>Energy charge</subject><subject>Exposure</subject><subject>Extraterrestrial radiation</subject><subject>Forming</subject><subject>Galactic cosmic rays</subject><subject>Health aspects</subject><subject>Health risks</subject><subject>Helium</subject><subject>Hematopoietic stem cells</subject><subject>Hematopoietic Stem Cells - cytology</subject><subject>Hematopoietic Stem Cells - metabolism</subject><subject>Hematopoietic Stem Cells - radiation effects</subject><subject>Hematopoietic system</subject><subject>High energy astronomy</subject><subject>Ion beams</subject><subject>Ion irradiation</subject><subject>Ionization</subject><subject>Ionizing radiation</subject><subject>Iron</subject><subject>Irradiation</subject><subject>Laboratories</subject><subject>Leukocytes (neutrophilic)</subject><subject>Lymphocytes</subject><subject>Male</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Monocytes</subject><subject>Nuclei</subject><subject>Nuclei (nuclear physics)</subject><subject>Oxidative stress</subject><subject>Oxidative Stress - radiation effects</subject><subject>Oxygen</subject><subject>Oxygen - adverse effects</subject><subject>Peripheral blood</subject><subject>Pharmaceutical sciences</subject><subject>Physiological aspects</subject><subject>Platelets</subject><subject>Progenitor cells</subject><subject>Protons</subject><subject>Radiation</subject><subject>Radiation damage</subject><subject>Radiation dosage</subject><subject>Reactive oxygen species</subject><subject>Reactive Oxygen Species - metabolism</subject><subject>Relative biological effectiveness (RBE)</subject><subject>Research and Analysis Methods</subject><subject>Rodents</subject><subject>Space missions</subject><subject>Stem cell transplantation</subject><subject>Stem cells</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><sourceid>DOA</sourceid><recordid>eNqNk99v0zAQxyMEYmPwHyCwhITgocWOE9t5Qao6YJWKKgHj1bo6l9RVEndxAtt_j7tmU4P2MFmRL87nvr7cjyh6zeiUcck-bV3fNlBNd67BKWWpopl8Ep2yjMcTEVP-9Mg-iV54v6U05UqI59FJLLmQgian0eXS_SXnzqMnriCr65sSG7Jw4WlbyC10Nthz6D2Smek7JOdQQ4mkc-QCa-jczlnsrCFzrCpPbEO-W4Mvo2cFVB5fDftZdPn1y6_5xWS5-raYz5YTIzPWTQpWSBVzMNwIxnLMkOGaY55xKRJVrBUtYqayGKhUKg3vkK-zQhlQqQQmgZ9Fbw-6u8p5PWTEa6Yoo7FI4iwQiwORO9jqXWtraG-0A6tvD1xbamhD_BVqngCotZB5UqhESqEEU6niSppcSVA0aH0ebuvXNeYGm66FaiQ6_tLYjS7dH51knIZaBIEPg0Drrnr0na6tNyFx0KDrb-NWoTJUicegLOFcsb3qu__QhxMxUCWEf7VN4UKIZi-qZ0kqJM-USAM1fYAKK8famtBphQ3nI4ePI4fAdHjdlaFjvF78_PF4dvV7zL4_YjcIVbfxrur3_ejHYHIATeu8b7G4rwejej8od9nQ-0HRw6AEtzfHtbx3upsM_g8nrQsl</recordid><startdate>20160701</startdate><enddate>20160701</enddate><creator>Chang, Jianhui</creator><creator>Luo, Yi</creator><creator>Wang, Yingying</creator><creator>Pathak, Rupak</creator><creator>Sridharan, Vijayalakshmi</creator><creator>Jones, Tamako</creator><creator>Mao, Xiao Wen</creator><creator>Nelson, Gregory</creator><creator>Boerma, Marjan</creator><creator>Hauer-Jensen, Martin</creator><creator>Zhou, Daohong</creator><creator>Shao, Lijian</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20160701</creationdate><title>Low Doses of Oxygen Ion Irradiation Cause Acute Damage to Hematopoietic Cells in Mice</title><author>Chang, Jianhui ; Luo, Yi ; Wang, Yingying ; Pathak, Rupak ; Sridharan, Vijayalakshmi ; Jones, Tamako ; Mao, Xiao Wen ; Nelson, Gregory ; Boerma, Marjan ; Hauer-Jensen, Martin ; Zhou, Daohong ; Shao, Lijian</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c791t-f1f7823ac3c611de9e1eb3ed937648fb80f21892a07885fb8adb9f8ca857a17a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Acute effects</topic><topic>Analysis</topic><topic>Animals</topic><topic>Apoptosis</topic><topic>Astronauts</topic><topic>Biological effects</topic><topic>Biology and life sciences</topic><topic>Blood</topic><topic>Blood Cell Count</topic><topic>Blood cells</topic><topic>Bone marrow</topic><topic>Cell cycle</topic><topic>Cell Cycle - 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radiation effects</topic><topic>Oxygen</topic><topic>Oxygen - adverse effects</topic><topic>Peripheral blood</topic><topic>Pharmaceutical sciences</topic><topic>Physiological aspects</topic><topic>Platelets</topic><topic>Progenitor cells</topic><topic>Protons</topic><topic>Radiation</topic><topic>Radiation damage</topic><topic>Radiation dosage</topic><topic>Reactive oxygen species</topic><topic>Reactive Oxygen Species - metabolism</topic><topic>Relative biological effectiveness (RBE)</topic><topic>Research and Analysis Methods</topic><topic>Rodents</topic><topic>Space missions</topic><topic>Stem cell transplantation</topic><topic>Stem cells</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Chang, Jianhui</creatorcontrib><creatorcontrib>Luo, Yi</creatorcontrib><creatorcontrib>Wang, Yingying</creatorcontrib><creatorcontrib>Pathak, Rupak</creatorcontrib><creatorcontrib>Sridharan, Vijayalakshmi</creatorcontrib><creatorcontrib>Jones, Tamako</creatorcontrib><creatorcontrib>Mao, Xiao Wen</creatorcontrib><creatorcontrib>Nelson, Gregory</creatorcontrib><creatorcontrib>Boerma, Marjan</creatorcontrib><creatorcontrib>Hauer-Jensen, Martin</creatorcontrib><creatorcontrib>Zhou, Daohong</creatorcontrib><creatorcontrib>Shao, Lijian</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Opposing Viewpoints</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Nursing & Allied Health Database</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Meteorological & Geoastrophysical Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology 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>Materials Science & Engineering Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>Advanced Technologies & Aerospace Collection</collection><collection>Agricultural & Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Materials Science Collection</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Materials Science Database</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Meteorological & Geoastrophysical Abstracts - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Chang, Jianhui</au><au>Luo, Yi</au><au>Wang, Yingying</au><au>Pathak, Rupak</au><au>Sridharan, Vijayalakshmi</au><au>Jones, Tamako</au><au>Mao, Xiao Wen</au><au>Nelson, Gregory</au><au>Boerma, Marjan</au><au>Hauer-Jensen, Martin</au><au>Zhou, Daohong</au><au>Shao, Lijian</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Low Doses of Oxygen Ion Irradiation Cause Acute Damage to Hematopoietic Cells in Mice</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2016-07-01</date><risdate>2016</risdate><volume>11</volume><issue>7</issue><spage>e0158097</spage><epage>e0158097</epage><pages>e0158097-e0158097</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>One of the major health risks to astronauts is radiation on long-duration space missions. Space radiation from sun and galactic cosmic rays consists primarily of 85% protons, 14% helium nuclei and 1% high-energy high-charge (HZE) particles, such as oxygen (16O), carbon, silicon, and iron ions. HZE particles exhibit dense linear tracks of ionization associated with clustered DNA damage and often high relative biological effectiveness (RBE). Therefore, new knowledge of risks from HZE particle exposures must be obtained. In the present study, we investigated the acute effects of low doses of 16O irradiation on the hematopoietic system. Specifically, we exposed C57BL/6J mice to 0.1, 0.25 and 1.0 Gy whole body 16O (600 MeV/n) irradiation and examined the effects on peripheral blood (PB) cells, and bone marrow (BM) hematopoietic stem cells (HSCs) and hematopoietic progenitor cells (HPCs) at two weeks after the exposure. The results showed that the numbers of white blood cells, lymphocytes, monocytes, neutrophils and platelets were significantly decreased in PB after exposure to 1.0 Gy, but not to 0.1 or 0.25 Gy. However, both the frequency and number of HPCs and HSCs were reduced in a radiation dose-dependent manner in comparison to un-irradiated controls. Furthermore, HPCs and HSCs from irradiated mice exhibited a significant reduction in clonogenic function determined by the colony-forming and cobblestone area-forming cell assays. These acute adverse effects of 16O irradiation on HSCs coincided with an increased production of reactive oxygen species (ROS), enhanced cell cycle entry of quiescent HSCs, and increased DNA damage. However, none of the 16O exposures induced apoptosis in HSCs. These data suggest that exposure to low doses of 16O irradiation induces acute BM injury in a dose-dependent manner primarily via increasing ROS production, cell cycling, and DNA damage in HSCs. This finding may aid in developing novel strategies in the protection of the hematopoietic system from space radiation.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>27367604</pmid><doi>10.1371/journal.pone.0158097</doi><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2016-07, Vol.11 (7), p.e0158097-e0158097 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_1801026429 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; Free Full-Text Journals in Chemistry; Public Library of Science (PLoS) |
| subjects | Acute effects Analysis Animals Apoptosis Astronauts Biological effects Biology and life sciences Blood Blood Cell Count Blood cells Bone marrow Cell cycle Cell Cycle - radiation effects Cells (biology) Cosmic rays Deoxyribonucleic acid DNA DNA Damage DNA methylation Dose-Response Relationship, Radiation Drug dosages Energy charge Exposure Extraterrestrial radiation Forming Galactic cosmic rays Health aspects Health risks Helium Hematopoietic stem cells Hematopoietic Stem Cells - cytology Hematopoietic Stem Cells - metabolism Hematopoietic Stem Cells - radiation effects Hematopoietic system High energy astronomy Ion beams Ion irradiation Ionization Ionizing radiation Iron Irradiation Laboratories Leukocytes (neutrophilic) Lymphocytes Male Mice Mice, Inbred C57BL Monocytes Nuclei Nuclei (nuclear physics) Oxidative stress Oxidative Stress - radiation effects Oxygen Oxygen - adverse effects Peripheral blood Pharmaceutical sciences Physiological aspects Platelets Progenitor cells Protons Radiation Radiation damage Radiation dosage Reactive oxygen species Reactive Oxygen Species - metabolism Relative biological effectiveness (RBE) Research and Analysis Methods Rodents Space missions Stem cell transplantation Stem cells |
| title | Low Doses of Oxygen Ion Irradiation Cause Acute Damage to Hematopoietic Cells in Mice |
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