{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T20:13:41Z","timestamp":1791922421115,"version":"4.3.4"},"reference-count":46,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2022,1,14]],"date-time":"2022-01-14T00:00:00Z","timestamp":1642118400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Atomic Energy of Canada Limited\u2019s Federal Nuclear Science &amp; Technology Work Plan","award":["FST-51320.50.19.03"],"award-info":[{"award-number":["FST-51320.50.19.03"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Theoretical evaluations indicate the radiation weighting factor for thermal neutrons differs from the current International Commission on Radiological Protection (ICRP) recommended value of 2.5, which has radiation protection implications for high-energy radiotherapy, inside spacecraft, on the lunar or Martian surface, and in nuclear reactor workplaces. We examined the relative biological effectiveness (RBE) of DNA damage generated by thermal neutrons compared to gamma radiation. Whole blood was irradiated by 64 meV thermal neutrons from the National Research Universal reactor. DNA damage and erroneous DNA double-strand break repair was evaluated by dicentric chromosome assay (DCA) and cytokinesis-block micronucleus (CBMN) assay with low doses ranging 6\u201385 mGy. Linear dose responses were observed. Significant DNA aberration clustering was found indicative of high ionizing density radiation. When the dose contribution of both the 14N(n,p)14C and 1H(n,\u03b3)2H capture reactions were considered, the DCA and the CBMN assays generated similar maximum RBE values of 11.3 \u00b1 1.6 and 9.0 \u00b1 1.1, respectively. Consequently, thermal neutron RBE is approximately four times higher than the current ICRP radiation weighting factor value of 2.5. This lends support to bimodal peaks in the quality factor for RBE neutron energy response, underlining the importance of radiological protection against thermal neutron exposures.<\/jats:p>","DOI":"10.3390\/ijms23020878","type":"journal-article","created":{"date-parts":[[2022,1,14]],"date-time":"2022-01-14T12:34:04Z","timestamp":1642163644000},"page":"878","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["High-Accuracy Relative Biological Effectiveness Values Following Low-Dose Thermal Neutron Exposures Support Bimodal Quality Factor Response with Neutron Energy"],"prefix":"10.3390","volume":"23","author":[{"given":"Laura C.","family":"Paterson","sequence":"first","affiliation":[{"name":"Canadian Nuclear Laboratories (CNL), Chalk River, ON K0J 1J0, Canada"},{"name":"Division of Experimental Medicine, McGill University, Montreal, QC H4A 3J1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy","family":"Festarini","sequence":"additional","affiliation":[{"name":"Canadian Nuclear Laboratories (CNL), Chalk River, ON K0J 1J0, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marilyne","family":"Stuart","sequence":"additional","affiliation":[{"name":"Canadian Nuclear Laboratories (CNL), Chalk River, ON K0J 1J0, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fawaz","family":"Ali","sequence":"additional","affiliation":[{"name":"Canadian Nuclear Laboratories (CNL), Chalk River, ON K0J 1J0, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christie","family":"Costello","sequence":"additional","affiliation":[{"name":"Canadian Nuclear Laboratories (CNL), Chalk River, ON K0J 1J0, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chad","family":"Boyer","sequence":"additional","affiliation":[{"name":"Canadian Nuclear Laboratories (CNL), Chalk River, ON K0J 1J0, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronald","family":"Rogge","sequence":"additional","affiliation":[{"name":"Canadian Nuclear Laboratories (CNL), Chalk River, ON K0J 1J0, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norma","family":"Ybarra","sequence":"additional","affiliation":[{"name":"Division of Experimental Medicine, McGill University, Montreal, QC H4A 3J1, Canada"},{"name":"Medical Physics Unit, Montreal, QC H4A 3J1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7084-1425","authenticated-orcid":false,"given":"John","family":"Kildea","sequence":"additional","affiliation":[{"name":"Medical Physics Unit, Montreal, QC H4A 3J1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard B.","family":"Richardson","sequence":"additional","affiliation":[{"name":"Canadian Nuclear Laboratories (CNL), Chalk River, ON K0J 1J0, Canada"},{"name":"Medical Physics Unit, Montreal, QC H4A 3J1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,1,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"6162","DOI":"10.1118\/1.4931963","article-title":"Measuring neutron spectra in radiotherapy using the nested neutron spectrometer","volume":"42","author":"Maglieri","year":"2015","journal-title":"Med. Phys."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"438","DOI":"10.1038\/nrc3069","article-title":"Assessing the risk of second malignancies after modern radiotherapy","volume":"11","author":"Newhauser","year":"2011","journal-title":"Nat. Cancer"},{"key":"ref_3","first-page":"55","article-title":"The Canadian Neutron-Induced Carcinogenic Effects Research Program\u2014A research program to investigate neutron relative biological effectiveness for carcinogenesis with a particular focus on secondary (by-product) neutrons in high-energy radiation therapy","volume":"6","author":"Kildea","year":"2017","journal-title":"Radiat. Environ. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1093\/oxfordjournals.rpd.a032071","article-title":"Feasibility of creating \u201cCANDU-Like\u201d workplace neutron fields in an existing irradiation facility","volume":"72","author":"Nunes","year":"1997","journal-title":"Radiat. Prot. Dosim."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.lssr.2019.02.008","article-title":"On the decision making criteria for cis-lunar reference mission scenarios","volume":"21","author":"Lewis","year":"2019","journal-title":"Life Sci. Space Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.lssr.2015.05.001","article-title":"Monte Carlo simulations of the secondary neutron ambient and effective dose equivalent rates from surface to suborbital altitudes and low Earth orbit","volume":"6","author":"Richardson","year":"2015","journal-title":"Life Sci. Space Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1093\/rpd\/nch216","article-title":"The energy spectrum of cosmic-ray induced neutrons measured on an airplane over a wide range of altitude and latitude","volume":"110","author":"Goldhagen","year":"2004","journal-title":"Radiat. Prot. Dosim."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"eaaz1334","DOI":"10.1126\/sciadv.aaz1334","article-title":"First measurements of the radiation dose on the lunar surface","volume":"6","author":"Zhang","year":"2020","journal-title":"Sci. Adv."},{"key":"ref_9","unstructured":"IAEA (2001). Current Status of Neutron Capture Therapy, IAEA."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"ICRP (2003). Relative biological effectiveness (RBE), quality factor (Q), and radiation weighting factor (wR): ICRP publication 92. Ann. ICRP, 33, 1\u2013121.","DOI":"10.1016\/S0146-6453(03)00024-1"},{"key":"ref_11","first-page":"85","article-title":"Quality factors and ambient dose equivalent for neutrons based on the new ICRP recommendations","volume":"40","author":"Schuhmacher","year":"1992","journal-title":"Radiat. Prot. Dosim."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1037","DOI":"10.1088\/1361-6498\/aaca9f","article-title":"Dosimetric and microdosimetric analyses for blood exposed to reactor-derived thermal neutrons","volume":"38","author":"Ali","year":"2018","journal-title":"J. Radiol. Prot."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1093\/oxfordjournals.rpd.a079409","article-title":"Conversion and quality factors relating neutron fluence and dosimetric quantities","volume":"10","author":"Cross","year":"1985","journal-title":"Radiat. Prot. Dosim."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1","DOI":"10.2307\/3575939","article-title":"Neutron quality parameters versus energy below 4 MeV from microdosimetric calculations","volume":"93","author":"Stinchcomb","year":"1983","journal-title":"Radiat. Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"480","DOI":"10.1667\/RADE-20-00213.1","article-title":"Neutron radiobiology and dosimetry","volume":"195","author":"Stricklin","year":"2021","journal-title":"Radiat. Res."},{"key":"ref_16","first-page":"1046","article-title":"Cytogenetic effects induced by neutrons in human peripheral blood lymphocytes in vitro. I. Dose-effect relationship for different types of chromosome aberrations when exposed to neutrons with different energies","volume":"15","author":"Zherbin","year":"1979","journal-title":"\u0413\u0435\u043d\u0435\u0442\u0438\u043a\u0430"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1088\/0952-4746\/32\/3\/261","article-title":"Chromosomal aberrations in peripheral blood lymphocytes exposed to a mixed beam of low energy neutrons and gamma radiation","volume":"32","author":"Wojcik","year":"2012","journal-title":"J. Radiol. Prot."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1007\/s00411-012-0449-2","article-title":"RBE of thermal neutrons for induction of chromosome aberrations in human lymphocytes","volume":"52","author":"Schmid","year":"2012","journal-title":"Radiat. Environ. Biophys."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1007\/s00411-006-0051-6","article-title":"Effective dose of A-bomb radiation in Hiroshima and Nagasaki as assessed by chromosomal effectiveness of spectrum energy photons and neutrons","volume":"45","author":"Sasaki","year":"2006","journal-title":"Radiat. Environ. Biophys."},{"key":"ref_20","unstructured":"IAEA (2011). Cytogenetic Dosimetry: Applications in Preparedness for and Response to Radiation Emergencies, IAEA."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1097\/HP.0b013e3182307758","article-title":"Validation of QuickScan dicentric chromosome analysis for high throughput radiation biological dosimetry","volume":"102","author":"Flegal","year":"2012","journal-title":"Health Phys."},{"key":"ref_22","unstructured":"Ishihara, T., and Sasaki, M.S. (1983). Chromosome aberrations in human lymphocytes: Effect of radiation quality, dose, and dose rate. Radiation-Induced Chromosome Damage in Man, AR Liss."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1007\/BF01323712","article-title":"Quantitative analysis of the chromosome damage at first division of human lymphocytes after 60Co gamma-irradiation","volume":"22","author":"Bauchinger","year":"1983","journal-title":"Radiat. Environ. Biophys."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"975","DOI":"10.1080\/09553008914552431","article-title":"Induction of chromosome aberrations in human lymphocytes by monochromatic X-rays of quantum energy between 4\u00b78 and 14\u00b76 keV","volume":"56","author":"Sasaki","year":"1989","journal-title":"Int. J. Radiat. Biol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"205011","DOI":"10.1088\/1361-6560\/ac2998","article-title":"Towards the characterization of neutron carcinogenesis through direct action simulations of clustered DNA damage","volume":"66","author":"Montgomery","year":"2021","journal-title":"Phys. Med. Biol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1093\/jrr\/rrs079","article-title":"Relative biological effects of neutron mixed-beam irradiation for boron neutron capture therapy on cell survival and DNA double-strand breaks in cultured mammalian cells","volume":"54","author":"Okumura","year":"2012","journal-title":"J. Radiat. Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/S1383-5718(02)00249-8","article-title":"HUMN project: Detailed description of the scoring criteria for the cytokinesis-block micronucleus assay using isolated human lymphocyte cultures","volume":"534","author":"Fenech","year":"2003","journal-title":"Mutat. Res. Toxicol. Environ. Mutagen."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/0027-5107(93)90049-L","article-title":"The cytokinesis-block micronucleus technique: A detailed description of the method and its application to genotoxicity studies in human populations","volume":"285","author":"Fenech","year":"1993","journal-title":"Mutat. Res. Mol. Mech. Mutagen."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1667\/RR15528.2","article-title":"Relative biological effectiveness and non-Poissonian distribution of dicentric chromosome aberrations following californium-252 neutron exposures of human peripheral blood lymphocytess","volume":"195","author":"Paterson","year":"2020","journal-title":"Radiat. Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1093\/rpd\/ncp119","article-title":"Validation of the cytokinesis-block micronucleus (CBMN) assay for use as a triage biological dosimetry tool","volume":"135","author":"McNamee","year":"2009","journal-title":"Radiat. Prot. Dosim."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1667\/RR2321.1","article-title":"Biological dosimetry by the triage dicentric chromosome assay: Potential implications for treatment","volume":"175","author":"Romm","year":"2011","journal-title":"Radiat. Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1080\/09553009414550381","article-title":"Micronuclei induced by fast neutrons versus 60Co gamma-rays in human peripheral blood lymphocytes","volume":"65","author":"Vral","year":"1994","journal-title":"Int. J. Radiat. Biol."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Lehman, R.R., and Archer, K.J. (2019). Penalized negative binomial models for modeling an overdispersed count outcome with a high-dimensional predictor space: Application predicting micronuclei frequency. PLoS ONE, 14.","DOI":"10.1371\/journal.pone.0209923"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1269\/jrr.42.91","article-title":"Neutron-induced adaptive response studied in go human lymphocytes using the comet assay","volume":"42","author":"Gajendiran","year":"2001","journal-title":"J. Radiat. Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"252","DOI":"10.2203\/dose-response.07-024.Rithidech","article-title":"Evidence for radiation hormesis after in vitro exposure of human lymphocytes to low doses of ionizing radiation","volume":"6","author":"Rithidech","year":"2008","journal-title":"Dose-Response"},{"key":"ref_36","first-page":"1","article-title":"Relative biological effectiveness (RBE) and dose rate dependent ratio of translocation to dicentric chromosome yield in 252Cf neutrons","volume":"2","author":"Tanaka","year":"2009","journal-title":"Indian J. Sci. Technol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1667\/0033-7587(2000)154[0307:TEOMNA]2.0.CO;2","article-title":"The effectiveness of monoenergetic neutrons at 565 keV in producing dicentric chromosomes in human lymphocytes at low doses","volume":"154","author":"Schmid","year":"2000","journal-title":"Radiat. Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1667\/0033-7587(2002)157[0453:RBEOKN]2.0.CO;2","article-title":"Relative biological effectiveness of 144 keV neutrons in producing dicentric chromosomes in human lymphocytes compared with 60Co gamma rays under head-to-head conditions","volume":"157","author":"Schmid","year":"2002","journal-title":"Radiat. Res."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1080\/095530098142383","article-title":"Apoptosis induced by fast neutrons versus 60Co gamma-rays in human peripheral blood lymphocytes","volume":"73","author":"Vral","year":"1998","journal-title":"Int. J. Radiat. Biol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1016\/0360-3016(95)02029-2","article-title":"A review of human cell radiosensitivity in vitro","volume":"34","author":"Deschavanne","year":"1996","journal-title":"Int. J. Radiat. Oncol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1007\/s00411-003-0200-0","article-title":"RBE of nearly monoenergetic neutrons at energies of 36 keV\u201314.6 MeV for induction of dicentrics in human lymphocytes","volume":"42","author":"Schmid","year":"2003","journal-title":"Radiat. Environ. Biophys."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"443","DOI":"10.3109\/09553002.2015.1012305","article-title":"Evaluation of the annual Canadian biodosimetry network intercomparisons","volume":"91","author":"Wilkins","year":"2015","journal-title":"Int. J. Radiat. Biol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1080\/09553007814550751","article-title":"Chromosome aberrations induced in human lymphocytes by radiation from 252Cf","volume":"34","author":"Lloyd","year":"1978","journal-title":"Int. J. Radiat. Biol. Relat. Stud. Phys. Chem. Med."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"561","DOI":"10.2307\/3576488","article-title":"Chromosome aberrations induced in human lymphocytes by D-T neutrons","volume":"98","author":"Lloyd","year":"1984","journal-title":"Radiat. Res."},{"key":"ref_45","unstructured":"Szluinska, M., Edwards, A.A., and Lloyd, D.C. (2005). Statistical Methods for Biological Dosimetry, HPA Radiation Protection Division."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1097\/01.HP.0000346305.84577.b4","article-title":"Dose estimation software for radiation biodosimetry","volume":"98","author":"Ainsbury","year":"2010","journal-title":"Health Phys."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/2\/878\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T14:02:22Z","timestamp":1760364142000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/2\/878"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,1,14]]},"references-count":46,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2022,1]]}},"alternative-id":["ijms23020878"],"URL":"https:\/\/doi.org\/10.3390\/ijms23020878","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,1,14]]}}}