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1
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Romero I, Mandina Cardoso T, Cabitto M, Deminge M, Rearte JF, Vaquero H, Farias de Lima F, Esposito Mendes M, Melo Silva L, Lafuente-Álvarez EF, Rada-Tarifa A, Verdejo V, Radl A, Saavedra N, Santibañez M, Brenes Obando N, Chaves-Campos FA, Ortíz F, Valle L, González Mesa JE, Bastidas A, Muñoz-Velástegui G, Arceo-Maldonado C, Guerrero-Carbajal YC, Aguilar-Coronel S, Monjagata N, Espinoza-Zevallos M, Martínez-López W, Mechoso B, Di Tomaso MV, Falcón de Vargas A, García Lima O. LBDNet inter-laboratory comparison at high doses of ionizing radiation using the dicentric plus caffeine assay. Int J Radiat Biol 2025:1-17. [PMID: 40323900 DOI: 10.1080/09553002.2025.2494554] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2025] [Revised: 03/24/2025] [Accepted: 04/10/2025] [Indexed: 05/07/2025]
Abstract
PURPOSE To assess the performance of the LBDNet laboratories in estimating dose over 5 Gy of ionizing radiation using the dicentric chromosome plus caffeine assay. MATERIALS AND METHODS Dose-response curve fitting: Peripheral blood was irradiated in vitro between 5 and 25 Gy. Then, the DC plus caffeine assay was carried out. Thirteen laboratories received and analyzed metaphase images. The linear dose-response curve was fitted for each laboratory. Dose estimation was performed analyzing coded metaphase images from three different irradiated samples (7.5, 15, 20 Gy) and using the fitted curve from every laboratory. RESULTS The dose estimation accuracy was within the expected dose ranges. The 76.9%, 84.6% and 69.2% of the estimated doses fell into the ± 20% of the true radiation dose. The 92.3%, 92.3%, and 61.5% of the 95% of the confidence interval of the estimated doses included the true radiation dose. The trueness was 0.9%, 4.4% and 9.6%. The Coefficients of Variation of the estimated doses were 14.5%, 16.1% and 17.8%. Results from only one laboratory were deemed questionable for dose estimation, based on the Z-score derived from robust methods. CONCLUSION The intercomparison study yielded satisfactory results; however, dose estimation accuracy tended to decrease, and variability between laboratory results increased as the dose level rose.
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Affiliation(s)
- Ivonne Romero
- Departamento de Ciencias Básicas, Facultad de Medicina, Universidad de La Frontera, Temuco, Chile
| | - Tania Mandina Cardoso
- Radiobiology Laboratory, Center for Radiation Protection and Hygiene (CPHR), La Habana, Cuba
| | - Mariana Cabitto
- Biological Dosimetry Laboratory, Nuclear Regulatory Authority (ARN), Buenos Aires, Argentina
| | - Mayra Deminge
- Biological Dosimetry Laboratory, Nuclear Regulatory Authority (ARN), Buenos Aires, Argentina
| | | | - Hernan Vaquero
- Biological Dosimetry Laboratory, Nuclear Regulatory Authority (ARN), Buenos Aires, Argentina
| | - Fabiana Farias de Lima
- Biological Dosimetry Laboratory, Centro Regional de Ciências Nucleares do Nordeste CRCN-NE/CNEN, Recife, Brazil
| | - Mariana Esposito Mendes
- Biological Dosimetry Laboratory, Centro Regional de Ciências Nucleares do Nordeste CRCN-NE/CNEN, Recife, Brazil
| | - Laís Melo Silva
- Biological Dosimetry Laboratory, Centro Regional de Ciências Nucleares do Nordeste CRCN-NE/CNEN, Recife, Brazil
- Universidade Federal de Pernambuco, Recife, Brasil
| | - Erika Flavia Lafuente-Álvarez
- Unidad de Citogenética - Instituto de Genética, Facultad de Medicina, Universidad Mayor de San Andrés, La Paz, Bolivia
| | - Ana Rada-Tarifa
- Unidad de Citogenética - Instituto de Genética, Facultad de Medicina, Universidad Mayor de San Andrés, La Paz, Bolivia
| | - Valentina Verdejo
- Cytogenetic Dosimetry Laboratory, Chilean Nuclear Energy Commission (CCHEN), Santiago, Chile
| | - Analia Radl
- Cytogenetic Dosimetry Laboratory, Chilean Nuclear Energy Commission (CCHEN), Santiago, Chile
| | - Nicolás Saavedra
- Departamento de Ciencias Básicas, Facultad de Medicina, Universidad de La Frontera, Temuco, Chile
| | - Mauricio Santibañez
- Laboratorio de Radiaciones Ionizantes, Departamento de Ciencias Físicas, Universidad de La Frontera, Temuco, Chile
| | - Nelson Brenes Obando
- Cytogenetics Laboratory, Health Research Institute, (INISA), San Pedro, Costa Rica
| | | | - Fernando Ortíz
- Cytogenetics Laboratory, Health Research Institute, (INISA), San Pedro, Costa Rica
| | - Luisa Valle
- Cytogenetics Laboratory, Health Research Institute, (INISA), San Pedro, Costa Rica
| | | | - Angela Bastidas
- Hospital de Especialidades Carlos Andrade Marín, Quito, Ecuador
| | | | - Carolina Arceo-Maldonado
- Departamento de Biología, Instituto Nacional de Investigaciones Nucleares (ININ), Ocoyoacac, México
| | | | | | - Norma Monjagata
- Instituto de Investigaciones en Ciencias de la Salud, Asunción, Paraguay
| | - Marco Espinoza-Zevallos
- Cytogenetics and Radiobiology Laboratory, Directorate of Services, Peruvian Nuclear Energy Institute, Lima, Perú
| | - Wilner Martínez-López
- Genetics Department and Biodosimetry Service, Instituto de Investigaciones Biológicas Clemente Estable, Montevideo, Uruguay
| | - Burix Mechoso
- Genetics Department and Biodosimetry Service, Instituto de Investigaciones Biológicas Clemente Estable, Montevideo, Uruguay
| | - María Vittoria Di Tomaso
- Genetics Department and Biodosimetry Service, Instituto de Investigaciones Biológicas Clemente Estable, Montevideo, Uruguay
| | - Aida Falcón de Vargas
- Hospital Vargas de Caracas, Vargas Medical School, Universidad Central de Venezuela. Hospital de Clínicas Caracas, Caracas, Venezuela
| | - Omar García Lima
- Radiobiology Laboratory, Center for Radiation Protection and Hygiene (CPHR), La Habana, Cuba
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Tamizh Selvan G, Venkatachalam P. Potentials of cytokinesis blocked micronucleus assay in radiation triage and biological dosimetry. J Genet Eng Biotechnol 2024; 22:100409. [PMID: 39674629 PMCID: PMC11381789 DOI: 10.1016/j.jgeb.2024.100409] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2023] [Revised: 02/04/2024] [Accepted: 08/06/2024] [Indexed: 09/11/2024]
Abstract
The measurement of micronucleus (MN) in the cytokinesis-block arrested binucleated cells has been extensively used as a biomarker in many radiation biology applications in specific biodosimetry. Following radiation casualties, medical management of exposed individuals begins with triage and biological dosimetry. The cytokinesis blocked micronucleus (CBMN) assay is the alternate for the gold standard dicentric chromosome assay in radiation dose assessment. In recent years, the CBMN assay has become well-validated and emerged as a method of choice for evaluating occupational and accidental exposures scenario. It is feasible due to its cost-effective, simple, and rapid dose assessment rather than a conventional chromosome aberration assay. PubMed search tool was used with keywords of MN, biodosimetry, radiotherapy and restricted to human samples. Since Fenech and Morely developed the assay, it has undergone many technical and technological reforms as a biomarker of various applications. In this review, we have abridged recent developments of the CBMN assay in radiation triage and biodosimetry, focusing on (a) the influence of variables on dose estimation, (b) the importance of baseline frequency and reported dose-response coefficient values among different laboratories, (c) inter-laboratory comparison and (d) its limitations and means to overcome them.
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Affiliation(s)
- G Tamizh Selvan
- Central Research Laboratory, K.S. Hegde Medical Academy, NITTE (Deemed to be University), Deralakatte, Mangalore, Karnataka, India.
| | - P Venkatachalam
- Department of Human Genetics, Sri Ramachandra Institute of Higher Education and Research (Deemed to be University), Chennai, India
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3
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González Mesa JE, Alem Glison D, Chaves-Campos FA, Ortíz Morales F, Valle Bourrouet L, Abarca Ramírez M, Verdejo V, Di Giorgio M, Radl A, Taja MR, Deminge M, Rada-Tarifa A, Lafuente-Alvarez E, Lima FFD, Hwang S, Esposito Mendes M, Mandina-Cardoso T, Muñoz-Velastegui G, Guerrero-Carbajal YC, Arceo Maldonado C, Monjagata N, Aguilar-Coronel S, Espinoza-Zevallos M, Falcon de Vargas A, Vittoria Di Tomaso M, Holladay B, Lima OG, Martínez-López W. LBDNet interlaboratory comparison for the dicentric chromosome assay by digitized image analysis applying weighted robust statistical methods. Int J Radiat Biol 2024; 100:1019-1028. [PMID: 38810111 DOI: 10.1080/09553002.2024.2356556] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2023] [Accepted: 05/13/2024] [Indexed: 05/31/2024]
Abstract
PURPOSE This interlaboratory comparison was conducted to evaluate the performance of the Latin-American Biodosimetry Network (LBDNet) in analyzing digitized images for scoring dicentric chromosomes from in vitro irradiated blood samples. The exercise also assessed the use of weighted robust algorithms to compensate the uneven expertise among the participating laboratories. METHODS Three sets of coded images obtained through the dicentric chromosome assay from blood samples irradiated at 1.5 Gy (sample A) and 4 Gy (sample B), as well as a non-irradiated whole blood sample (sample C), were shared among LBDNet laboratories. The images were captured using the Metafer4 platform coupled with the AutoCapt module. The laboratories were requested to perform triage scoring, conventional scoring, and dose estimation. The dose estimation was carried out using either their laboratory calibration curve or a common calibration curve. A comparative statistical analysis was conducted using a weighted robust Hampel algorithm and z score to compensate for uneven expertise in dicentric analysis and dose assessment among all laboratories. RESULTS Out of twelve laboratories, one had unsatisfactory estimated doses at 0 Gy, and two had unsatisfactory estimated doses at 1.5 Gy when using their own calibration curve and triage scoring mode. However, all doses were satisfactory at 4 Gy. Six laboratories had estimated doses within 95% uncertainty limits at 0 Gy, seven at 1.5 Gy, and four at 4 Gy. While the mean dose for sample C was significantly biased using robust algorithms, applying weights to compensate for the laboratory's analysis expertise reduced the bias by half. The bias from delivered doses was only notable for sample C. Using the common calibration curve for dose estimation reduced the standard deviation (s*) estimated by robust methods for all three samples. CONCLUSIONS The results underscore the significance of performing interlaboratory comparison exercises that involve digitized and electronically transmitted images, even when analyzing non-irradiated samples. In situations where the participating laboratories possess different levels of proficiency, it may prove essential to employ weighted robust algorithms to achieve precise outcomes.
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Affiliation(s)
| | - Diego Alem Glison
- Genetics Department and Biodosimetry Service, Instituto de Investigaciones Biológicas Clemente Estable, Montevideo, Uruguay
| | | | | | | | | | - Valentina Verdejo
- Cytogenetic Dosimetry Laboratory, Chilean Nuclear Energy Commission (CCHEN), Santiago, Chile
| | - Marina Di Giorgio
- Biological Dosimetry Laboratory, Nuclear Regulatory Authority (ARN), Buenos Aires, Argentina
| | - Analía Radl
- Biological Dosimetry Laboratory, Nuclear Regulatory Authority (ARN), Buenos Aires, Argentina
| | - María Rosa Taja
- Biological Dosimetry Laboratory, Nuclear Regulatory Authority (ARN), Buenos Aires, Argentina
| | - Mayra Deminge
- Biological Dosimetry Laboratory, Nuclear Regulatory Authority (ARN), Buenos Aires, Argentina
| | - Ana Rada-Tarifa
- Unidad de Citogenética - Instituto de Genética, Facultad de Medicina, Universidad Mayor de San Andrés, La Paz, Bolivia
| | - Erika Lafuente-Alvarez
- Unidad de Citogenética - Instituto de Genética, Facultad de Medicina, Universidad Mayor de San Andrés, La Paz, Bolivia
| | - Fabiana Farias de Lima
- Biological Dosimetry Laboratory, Northeast Regional Center for Nuclear Sciences CRCN-NE/CNEN, Rio de Janeiro, Brazil
| | - Suy Hwang
- Biological Dosimetry Laboratory, Northeast Regional Center for Nuclear Sciences CRCN-NE/CNEN, Rio de Janeiro, Brazil
| | - Mariana Esposito Mendes
- Biological Dosimetry Laboratory, Northeast Regional Center for Nuclear Sciences CRCN-NE/CNEN, Rio de Janeiro, Brazil
| | - Tania Mandina-Cardoso
- Radiobiology Laboratory, Center for Radiation Protection and Hygiene (CPHR), La Habana, Cuba
| | | | | | | | - Norma Monjagata
- Instituto de Investigaciones en Ciencias de la Salud, Asunción, Paraguay
| | | | - Marco Espinoza-Zevallos
- Cytogenetics and Radiobiology Laboratory, Directorate of Services, Peruvian Institute of Nuclear Energy, San Borja, Peru
| | - Aida Falcon de Vargas
- Vargas Hospital of Caracas. Hospital de Clínicas Caracas. Central University of Venezuela, Caracas, Venezuela
| | - Maria Vittoria Di Tomaso
- Genetics Department and Biodosimetry Service, Instituto de Investigaciones Biológicas Clemente Estable, Montevideo, Uruguay
| | - Bret Holladay
- Statistics Department, California Polytechnic State University, San Luis Obispo, CA, USA
| | - Omar García Lima
- Radiobiology Laboratory, Center for Radiation Protection and Hygiene (CPHR), La Habana, Cuba
| | - Wilner Martínez-López
- Genetics Department and Biodosimetry Service, Instituto de Investigaciones Biológicas Clemente Estable, Montevideo, Uruguay
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Gregoire E, Barquinero JF, Gruel G, Benadjaoud M, Martinez JS, Beinke C, Balajee A, Beukes P, Blakely WF, Dominguez I, Duy PN, Gil OM, Güçlü I, Guogyte K, Hadjidekova SP, Hadjidekova V, Hande P, Jang S, Lumniczky K, Meschini R, Milic M, Montoro A, Moquet J, Moreno M, Norton FN, Oestreicher U, Pajic J, Sabatier L, Sommer S, Testa A, Terzoudi G, Valente M, Venkatachalam P, Vral A, Wilkins RC, Wojcik A, Zafiropoulos D, Kulka U. RENEB Inter-Laboratory comparison 2017: limits and pitfalls of ILCs. Int J Radiat Biol 2021; 97:888-905. [PMID: 33970757 DOI: 10.1080/09553002.2021.1928782] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2020] [Revised: 04/01/2021] [Accepted: 05/06/2021] [Indexed: 10/21/2022]
Abstract
PURPOSE In case of a mass-casualty radiological event, there would be a need for networking to overcome surge limitations and to quickly obtain homogeneous results (reported aberration frequencies or estimated doses) among biodosimetry laboratories. These results must be consistent within such network. Inter-laboratory comparisons (ILCs) are widely accepted to achieve this homogeneity. At the European level, a great effort has been made to harmonize biological dosimetry laboratories, notably during the MULTIBIODOSE and RENEB projects. In order to continue the harmonization efforts, the RENEB consortium launched this intercomparison which is larger than the RENEB network, as it involves 38 laboratories from 21 countries. In this ILC all steps of the process were monitored, from blood shipment to dose estimation. This exercise also aimed to evaluate the statistical tools used to compare laboratory performance. MATERIALS AND METHODS Blood samples were irradiated at three different doses, 1.8, 0.4 and 0 Gy (samples A, C and B) with 4-MV X-rays at 0.5 Gy min-1, and sent to the participant laboratories. Each laboratory was requested to blindly analyze 500 cells per sample and to report the observed frequency of dicentric chromosomes per metaphase and the corresponding estimated dose. RESULTS This ILC demonstrates that blood samples can be successfully distributed among laboratories worldwide to perform biological dosimetry in case of a mass casualty event. Having achieved a substantial harmonization in multiple areas among the RENEB laboratories issues were identified with the available statistical tools, which are not capable to advantageously exploit the richness of results of a large ILCs. Even though Z- and U-tests are accepted methods for biodosimetry ILCs, setting the number of analyzed metaphases to 500 and establishing a tests' common threshold for all studied doses is inappropriate for evaluating laboratory performance. Another problem highlighted by this ILC is the issue of the dose-effect curve diversity. It clearly appears that, despite the initial advantage of including the scoring specificities of each laboratory, the lack of defined criteria for assessing the robustness of each laboratory's curve is a disadvantage for the 'one curve per laboratory' model. CONCLUSIONS Based on our study, it seems relevant to develop tools better adapted to the collection and processing of results produced by the participant laboratories. We are confident that, after an initial harmonization phase reached by the RENEB laboratories, a new step toward a better optimization of the laboratory networks in biological dosimetry and associated ILC is on the way.
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Affiliation(s)
- Eric Gregoire
- Institut de Radioprotection et de Sûreté Nucléaire, Fontenay-aux-Roses, France
| | | | - Gaetan Gruel
- Institut de Radioprotection et de Sûreté Nucléaire, Fontenay-aux-Roses, France
| | | | - Juan S Martinez
- Institut de Radioprotection et de Sûreté Nucléaire, Fontenay-aux-Roses, France
| | - Christina Beinke
- Bundeswehr Institute of Radiobiology affiliated to the University of Ulm, Munich, Germany
| | - Adayabalam Balajee
- Oak Ridge Institute for Science and Education (ORISE), Oak Ridge, TN, USA
| | | | - William F Blakely
- Armed Forces Radiobiology Research Institute, Uniformed Service University of the Health, Sciences, Bethesda, MD, USA
| | | | - Pham Ngoc Duy
- Center of Biotechnology, Nuclear Research Institute, Dalat city, Vietnam
| | - Octávia Monteiro Gil
- Centro de Ciências e Tecnologias Nucleares, Instituto Superior Técnico, Universidade de Lisboa, Bobadela-LRS, Portugal
| | - Inci Güçlü
- Turkish Atomic Energy Authority, Cekmece Nuclear Research and Training Center, Radiobiology Unit Yarımburgaz, Istanbul, Turkey
| | | | | | | | - Prakash Hande
- Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | | | - Katalin Lumniczky
- National Research Institute for Radiobiology & Radiohygiene, Budapest, Hungary
| | | | | | - Alegria Montoro
- Fundación para la Investigación del Hospital Universitario LA FE de la Comunidad Valenciana, Valencia, Spain
| | - Jayne Moquet
- Public Health England, Centre for Radiation Chemical and Environmental Hazards, Chilton, UK
| | - Mercedes Moreno
- Servicio Madrileño de Salud - Hospital General Universitario Gregorio Marañón, Madrid, Spain
| | - Farrah N Norton
- Radiobiology & Health, Canadian Nuclear Laboratories, Chalk River, Canada
| | - Ursula Oestreicher
- Federal Office for Radiation Protection (BfS), Oberschleissheim, Germany
| | - Jelena Pajic
- Serbian Institute of Occupational Health, Radiation Protection Center, Belgrade, Serbia
| | - Laure Sabatier
- PROCyTOX, Commissariat à l'Energie Atomique et aux Energies Alternatives, Fontenay aux-Roses, France and Université Paris-Saclay, France
| | - Sylwester Sommer
- Institute of Nuclear Chemistry and Technology (INCT), Warsaw, Poland
| | - Antonella Testa
- Agenzia Nazionale per le Nuove Tecnologie, L´Energia e lo Sviluppo Economico Sostenibile, Rome, Italy
| | - Georgia Terzoudi
- National Center for Scientific Research "Demokritos", NCSR"D", Athens, Greece
| | | | | | - Anne Vral
- Radiobiology Research Unit, Gent University, Gent, Belgium
| | | | - Andrzej Wojcik
- Institute Molecular Biosciences, Stockholm University, Stockholm, Sweden
| | | | - Ulrike Kulka
- Federal Office for Radiation Protection (BfS), Oberschleissheim, Germany
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5
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Abstract
The dicentric chromosome (DC) assay accurately quantifies exposure to radiation; however, manual and semi-automated assignment of DCs has limited its use for a potential large-scale radiation incident. The Automated Dicentric Chromosome Identifier and Dose Estimator (ADCI) software automates unattended DC detection and determines radiation exposures, fulfilling IAEA criteria for triage biodosimetry. This study evaluates the throughput of high-performance ADCI (ADCI-HT) to stratify exposures of populations in 15 simulated population scale radiation exposures. ADCI-HT streamlines dose estimation using a supercomputer by optimal hierarchical scheduling of DC detection for varying numbers of samples and metaphase cell images in parallel on multiple processors. We evaluated processing times and accuracy of estimated exposures across census-defined populations. Image processing of 1744 samples on 16,384 CPUs required 1 h 11 min 23 s and radiation dose estimation based on DC frequencies required 32 sec. Processing of 40,000 samples at 10 exposures from five laboratories required 25 h and met IAEA criteria (dose estimates were within 0.5 Gy; median = 0.07). Geostatistically interpolated radiation exposure contours of simulated nuclear incidents were defined by samples exposed to clinically relevant exposure levels (1 and 2 Gy). Analysis of all exposed individuals with ADCI-HT required 0.6–7.4 days, depending on the population density of the simulation.
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Mirrezaei E, Setayeshi S, Zakeri F, Baradaran S. CONSTRUCTION AND VALIDATION OF IN VITRO DOSE-RESPONSE CALIBRATION CURVE USING DICENTRIC CHROMOSOME ABERRATION. RADIATION PROTECTION DOSIMETRY 2020; 189:198-204. [PMID: 32195553 DOI: 10.1093/rpd/ncaa031] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/05/2019] [Revised: 01/27/2020] [Accepted: 02/09/2020] [Indexed: 06/10/2023]
Abstract
Cytogenetic biodosimetry is a well-known method for quantifying the absorbed dose based on measuring biological radiation effects. To correlate the induced chromosomal abberrations with the absorbed dose of the individuals, a reliable dose-response calibration curve should be established. This study aimed to use frequencies and distributions of radiation-induced dicentric chromosome aberrations to develop a standard dose-response calibration curve. Peripheral blood samples taken from six male donors irradiated by an X-ray generator up to 4 Gy were studied. Three different blood samples were irradiated by known doses, then scored blindly for verification of the proposed calibration curve. Dose estimation was also carried out for three real overexposed cases. The results showed good accordance with the other published curves. The constructed dose-response curve provides a reliable tool for biological dosimetry in accidental or occupational radiation exposures.
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Affiliation(s)
- Ehsan Mirrezaei
- Department of Energy Engineering and Physics, Amirkabir University of Technology (Tehran Polytechnic), Tehran 11365-3486, Iran
| | - Saeed Setayeshi
- Department of Energy Engineering and Physics, Amirkabir University of Technology (Tehran Polytechnic), Tehran 11365-3486, Iran
| | - Farideh Zakeri
- Nuclear Science and Technology Research Institute, Tehran 14155-1339, Iran
| | - Samaneh Baradaran
- Nuclear Science and Technology Research Institute, Tehran 14155-1339, Iran
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7
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Use of biological dosimetry to confirm radiation exposure: Case study. Radiat Phys Chem Oxf Engl 1993 2020. [DOI: 10.1016/j.radphyschem.2020.108683] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/24/2022]
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8
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Mendes ME, Mendonça JCGD, Hwang S, Giorgio MD, Lima FFD, Santos N. Calibration curves by 60Co with low dose rate are different in terms of dose estimation - a comparative study. Genet Mol Biol 2020; 43:e20180370. [PMID: 32105287 PMCID: PMC7231543 DOI: 10.1590/1678-4685-gmb-2018-0370] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2018] [Accepted: 12/17/2019] [Indexed: 01/08/2023] Open
Abstract
Biological dosimetry aims to estimate individual absorbed doses due ionizing
radiation exposure. The dicentric chromosomes are considered the most specific
biomarker for dose estimation. This study aimed to compare calibration curves
for linear low energy transfer (LET) radiation built from low dose rates and
whether they vary in terms of dose estimation. For that we did a search in the
literature of all calibration curves produced with low dose rates and we
simulated the dose estimation from pre-established dicentric’s frequencies. The
information on methodologies and cytogenetic results of each study were
analyzed. As expected dose rate influence β coefficients, especially at higher
doses. However, we have seen that some doses were not statistically different
but they should be, because there is a significant association between the
productions of dicentrics and dose rate. This comparative study reinforced the
robustness of the dicentric assay and its importance in biological dosimetry. We
also emphasized that the dose rate was an important factor in dose estimations.
Thus, intercomparison exercises should take into account the dose rates of the
participating laboratories, because the dose rates might explain why some
results of estimated doses fall outside the recommendations.
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Affiliation(s)
- Mariana Esposito Mendes
- Universidade Federal de Pernambuco, Departamento de Genética, Recife, Pernambuco, Brazil.,Centro Regional de Ciências Nucleares do Nordeste, Recife, Pernambuco, Brazil
| | | | - Suy Hwang
- Centro Regional de Ciências Nucleares do Nordeste, Recife, Pernambuco, Brazil
| | | | | | - Neide Santos
- Universidade Federal de Pernambuco, Departamento de Genética, Recife, Pernambuco, Brazil
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9
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Bolduc DL, Blakely WF, H Olsen C, Agay D, Mestries JC, Drouet M, Hérodin F. BABOON RADIATION QUALITY (MIXED-FIELD NEUTRON AND GAMMA, GAMMA ALONE) DOSE-RESPONSE MODEL SYSTEMS: ASSESSMENT OF H-ARS SEVERITY USING HAEMATOLOGIC BIOMARKERS. RADIATION PROTECTION DOSIMETRY 2019; 186:15-23. [PMID: 31330012 DOI: 10.1093/rpd/ncz048] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/31/2018] [Revised: 02/24/2019] [Indexed: 06/10/2023]
Abstract
Results from archived (1986 and 1996) experiments were used to establish a baboon radiation-quality dose-response database with haematology biomarker time-course data following exposure to mixed-fields (i.e. neutron to gamma ratio: 5.5; dose: 0-8 Gy) and 60Co gamma-ray exposures (0-15 Gy). Time-course (i.e. 0-40 d) haematology changes for relevant blood-cell types for both mixed-field (neutron to gamma ratio = 5.5) and gamma ray alone were compared and models developed that showed significant differences using the maximum likehood ratio test. A consensus METREPOL-like haematology ARS (H-ARS) severity scoring system for baboons was established using these results. The data for mixed-field and the gamma only cohorts appeared similar, and so the cohorts were pooled into a single consensus H-ARS severity scoring system. These findings provide proof-of-concept for the use of a METREPOL H-ARS severity scoring system following mixed-field and gamma exposures.
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Affiliation(s)
- David L Bolduc
- Uniformed Services University of the Health Sciences, Armed Forces Radiobiology Research Institute, Scientific Research Department, Bethesda, MD, USA
| | - William F Blakely
- Uniformed Services University of the Health Sciences, Armed Forces Radiobiology Research Institute, Scientific Research Department, Bethesda, MD, USA
| | - Cara H Olsen
- Uniformed Services University of the Health Sciences, Preventive Medicine and Biostatistics Department, Bethesda, MD, USA
| | - Diane Agay
- Effets Biologiques des Rayonnements Département, Institut de Recherche Biomédicale des Armées, Brétigny sur Orge, France
| | - Jean-Claude Mestries
- Effets Biologiques des Rayonnements Département, Institut de Recherche Biomédicale des Armées, Brétigny sur Orge, France
| | - Michel Drouet
- Effets Biologiques des Rayonnements Département, Institut de Recherche Biomédicale des Armées, Brétigny sur Orge, France
| | - Francis Hérodin
- Effets Biologiques des Rayonnements Département, Institut de Recherche Biomédicale des Armées, Brétigny sur Orge, France
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Abe Y, Yoshida MA, Fujioka K, Kurosu Y, Ujiie R, Yanagi A, Tsuyama N, Miura T, Inaba T, Kamiya K, Sakai A. Dose-response curves for analyzing of dicentric chromosomes and chromosome translocations following doses of 1000 mGy or less, based on irradiated peripheral blood samples from five healthy individuals. JOURNAL OF RADIATION RESEARCH 2018; 59:35-42. [PMID: 29040682 PMCID: PMC5786284 DOI: 10.1093/jrr/rrx052] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/22/2017] [Indexed: 05/03/2023]
Abstract
In terms of biological dosimetry at the time of radiation exposure, the dicentric chromosome (Dic) assay (DCA) is the gold standard for assessing for the acute phase and chromosome translocation (Tr) analysis is the gold standard for assessing the chronic phase. It is desirable to have individual dose-response curves (DRCs) for each laboratory because the analysis criteria differ between laboratories. We constructed the DRCs for radiation dose estimation (with three methods) using peripheral blood (PB) samples from five healthy individuals. Aliquots were irradiated with one of eight gamma-ray doses (0, 10, 20, 50, 100, 200, 500 or 1000 mGy), then cultured for 48 h. The number of chromosome aberrations (CAs) was analyzed by DCA, using Giemsa staining and centromere-fluorescence in situ hybridization (centromere-FISH) and by chromosome painting (chromosome pairs 1, 2 and 4) for Tr analysis. In DCA, there was large variation between individuals in the frequency of Dics formed, and the slopes of the DRCs were different. In Tr analysis, although variation was observed in the frequency of Tr, the slopes of the DRCs were similar after adjusting the background for age. Good correlation between the irradiation dose and the frequency of CAs formed was observed with these three DRCs. However, performing three different biological dosimetry assays simultaneously on PB from five donors nonetheless results in variation in the frequency of CAs formed, especially at doses of 50 mGy or less, highlighting the difficulty of biological dosimetry using these methods. We conclude that it might be difficult to construct universal DRCs.
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Affiliation(s)
- Yu Abe
- Department of Radiation Life Sciences, Fukushima Medical University School of Medicine, 1 Hikarigaoka, Fukushima, 960–1295, Japan
| | - Mitsuaki A Yoshida
- Department of Radiation Biology, Institute of Radiation Emergency Medicine, Hirosaki University, Hirosaki, 036-8564, Japan
| | - Kurumi Fujioka
- Department of Molecular Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, 734-8553, Japan
| | - Yumiko Kurosu
- Department of Radiation Life Sciences, Fukushima Medical University School of Medicine, 1 Hikarigaoka, Fukushima, 960–1295, Japan
| | - Risa Ujiie
- Department of Radiation Life Sciences, Fukushima Medical University School of Medicine, 1 Hikarigaoka, Fukushima, 960–1295, Japan
| | - Aki Yanagi
- Department of Radiation Life Sciences, Fukushima Medical University School of Medicine, 1 Hikarigaoka, Fukushima, 960–1295, Japan
| | - Naohiro Tsuyama
- Department of Radiation Life Sciences, Fukushima Medical University School of Medicine, 1 Hikarigaoka, Fukushima, 960–1295, Japan
| | - Tomisato Miura
- Department of Pathologic Analysis, Hirosaki University Graduate School of Health Sciences, Hirosaki, 036-8564, Japan
| | - Toshiya Inaba
- Department of Molecular Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, 734-8553, Japan
| | - Kenji Kamiya
- Department of Experimental Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan
| | - Akira Sakai
- Department of Radiation Life Sciences, Fukushima Medical University School of Medicine, 1 Hikarigaoka, Fukushima, 960–1295, Japan
- Corresponding author. Department of Radiation Life Sciences, Fukushima Medical University School of Medicine, 1 Hikarigaoka, Fukushima, 960–1295, Japan. Tel: +81-24-547-1420; Fax: +81-24-547-1940;
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11
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Liu JX, Pan Y, Ruan JL, Piao C, Su X. Intercomparison in Cytogenetic Dosimetry among 22 Laboratories in China. Genome Integr 2016; 7:6. [PMID: 28217282 PMCID: PMC5292918 DOI: 10.4103/2041-9414.197164] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
Abstract
As part of a regional International Atomic Energy Agency-coordinated research project with the support from the National Health and Family Planning Commission of China, 22 laboratories participated in the intercomparison in cytogenetic dosimetry in China. Slides for chromosomal aberrations were prepared by the Department of Radiation Epidemiology, National Institute for Radiological Protection, which organized the exercise. Slides were sent to the other participating laboratories through Express Mail Service. For estimates of dose, each laboratory scored the frequency of dicentrics plus centric rings chromosomes. The whole blood samples were irradiated with 60Co γ-rays (1.3 Gy, 2.4 Gy and 1.5 Gy, 2.6 Gy). Each laboratory got one group of the slides. Ten of the 44 estimates of dose fell within ±5% of the true physical dose, 12 fell within ±5-10%, 9 fell within ±10-15%, 12 fell within ±15-20%, while only one sample fell ± >20%. The evaluation of the respective dose was achieved by 21 laboratories.
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Affiliation(s)
- Jian Xiang Liu
- Chinese Center for Disease Control and Prevention Key Laboratory of Radiological Protection and Nuclear Emergency, Beijing 100088, China; National Institute for Radiological Protection, Chinese Center for Disease Control and Prevention, Beijing 100088, China; Chinese Center for Medical Response to Radiation Emergency, Ministry of Health, Beijing 100088, China
| | - Yan Pan
- Chinese Center for Disease Control and Prevention Key Laboratory of Radiological Protection and Nuclear Emergency, Beijing 100088, China; National Institute for Radiological Protection, Chinese Center for Disease Control and Prevention, Beijing 100088, China; Chinese Center for Medical Response to Radiation Emergency, Ministry of Health, Beijing 100088, China
| | - Jian Lei Ruan
- Chinese Center for Disease Control and Prevention Key Laboratory of Radiological Protection and Nuclear Emergency, Beijing 100088, China; National Institute for Radiological Protection, Chinese Center for Disease Control and Prevention, Beijing 100088, China; Chinese Center for Medical Response to Radiation Emergency, Ministry of Health, Beijing 100088, China
| | - Chunnan Piao
- Chinese Center for Disease Control and Prevention Key Laboratory of Radiological Protection and Nuclear Emergency, Beijing 100088, China; National Institute for Radiological Protection, Chinese Center for Disease Control and Prevention, Beijing 100088, China; Chinese Center for Medical Response to Radiation Emergency, Ministry of Health, Beijing 100088, China
| | - Xu Su
- Chinese Center for Disease Control and Prevention Key Laboratory of Radiological Protection and Nuclear Emergency, Beijing 100088, China; National Institute for Radiological Protection, Chinese Center for Disease Control and Prevention, Beijing 100088, China; Chinese Center for Medical Response to Radiation Emergency, Ministry of Health, Beijing 100088, China
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Romm H, Beinke C, Garcia O, Di Giorgio M, Gregoire E, Livingston G, Lloyd DC, Martìnez-Lopez W, Moquet JE, Sugarman SL, Wilkins RC, Ainsbury EA. A New Cytogenetic Biodosimetry Image Repository for the Dicentric Assay. RADIATION PROTECTION DOSIMETRY 2016; 172:192-200. [PMID: 27412509 DOI: 10.1093/rpd/ncw158] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/06/2023]
Abstract
The BioDoseNet was founded by the World Health Organization as a global network of biodosimetry laboratories for building biodosimetry laboratory capacities in countries. The newly established BioDoseNet image repository is a databank of ~25 000 electronically captured images of metaphases from the dicentric assay, which have been previously analysed by international experts. The detailed scoring results and dose estimations have, in most cases, already been published. The compilation of these images into one image repository provides a valuable tool for training and research purposes in biological dosimetry. No special software is needed to view and score the image galleries. For those new to the dicentric assay, the BioDoseNet Image Repository provides an introduction to and training for the dicentric assay. It is an excellent instrument for intra-laboratory training purposes or inter-comparisons between laboratories, as recommended by the International Organization for Standardisation standards. In the event of a radiation accident, the repository can also increase the surge capacity and reduce the turnaround time for dose estimations. Finally, it provides a mechanism for the discussion of scoring discrepancies in difficult cases.
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Affiliation(s)
- Horst Romm
- Bundesamt fuer Strahlenschutz, Neuherberg, Salzgitter, Germany
| | | | - Omar Garcia
- Centro de Protección e Higiene de las Radiaciones, Havana, Cuba
| | | | - Eric Gregoire
- Institut de Radioprotection et de Sureté Nucléaire, Fontenay-aux-Roses, France
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13
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Standards in biological dosimetry: A requirement to perform an appropriate dose assessment. MUTATION RESEARCH-GENETIC TOXICOLOGY AND ENVIRONMENTAL MUTAGENESIS 2015; 793:115-22. [DOI: 10.1016/j.mrgentox.2015.06.012] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/15/2015] [Accepted: 06/16/2015] [Indexed: 10/23/2022]
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14
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Perumal V, Sekaran TSG, Raavi V, Basheerudeen SAS, Kanagaraj K, Chowdhury AR, Paul SFD. Radiation signature on exposed cells: Relevance in dose estimation. World J Radiol 2015; 7:266-278. [PMID: 26435777 PMCID: PMC4585950 DOI: 10.4329/wjr.v7.i9.266] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/25/2015] [Revised: 07/03/2015] [Accepted: 08/03/2015] [Indexed: 02/06/2023] Open
Abstract
The radiation is considered as a double edged sword, as its beneficial and detrimental effects have been demonstrated. The potential benefits are being exploited to its maximum by adopting safe handling of radionuclide stipulated by the regulatory agencies. While the occupational workers are monitored by personnel monitoring devices, for general publics, it is not a regular practice. However, it can be achieved by using biomarkers with a potential for the radiation triage and medical management. An ideal biomarker to adopt in those situations should be rapid, specific, sensitive, reproducible, and able to categorize the nature of exposure and could provide a reliable dose estimation irrespective of the time of the exposures. Since cytogenetic markers shown to have many advantages relatively than other markers, the origins of various chromosomal abnormalities induced by ionizing radiations along with dose-response curves generated in the laboratory are presented. Current status of the gold standard dicentric chromosome assay, micronucleus assay, translocation measurement by fluorescence in-situ hybridization and an emerging protein marker the γ-H2AX assay are discussed with our laboratory data. With the wide choice of methods, an appropriate assay can be employed based on the net.
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15
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Wilkins RC, Beaton-Green LA, Lachapelle S, Kutzner BC, Ferrarotto C, Chauhan V, Marro L, Livingston GK, Boulay Greene H, Flegal FN. Evaluation of the annual Canadian biodosimetry network intercomparisons. Int J Radiat Biol 2015; 91:443-51. [PMID: 25670072 PMCID: PMC4487546 DOI: 10.3109/09553002.2015.1012305] [Citation(s) in RCA: 32] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
Abstract
PURPOSE To evaluate the importance of annual intercomparisons for maintaining the capacity and capabilities of a well-established biodosimetry network in conjunction with assessing efficient and effective analysis methods for emergency response. MATERIALS AND METHODS Annual intercomparisons were conducted between laboratories in the Canadian National Biological Dosimetry Response Plan. Intercomparisons were performed over a six-year period and comprised of the shipment of 10-12 irradiated, blinded blood samples for analysis by each of the participating laboratories. Dose estimates were determined by each laboratory using the dicentric chromosome assay (conventional and QuickScan scoring) and where possible the cytokinesis block micronucleus (CBMN) assay. Dose estimates were returned to the lead laboratory for evaluation and comparison. RESULTS Individual laboratories performed comparably from year to year with only slight fluctuations in performance. Dose estimates using the dicentric chromosome assay were accurate about 80% of the time and the QuickScan method for scoring the dicentric chromosome assay was proven to reduce the time of analysis without having a significant effect on the dose estimates. Although analysis with the CBMN assay was comparable to QuickScan scoring with respect to speed, the accuracy of the dose estimates was greatly reduced. CONCLUSIONS Annual intercomparisons are necessary to maintain a network of laboratories for emergency response biodosimetry as they evoke confidence in their capabilities.
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Affiliation(s)
- Ruth C Wilkins
- Health Canada, Environmental Radiation and Health Sciences Directorate , Ottawa, ON , Canada
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16
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Bakkiam D, Bhavani M, Anantha Kumar AA, Sonwani S, Venkatachalam P, Sivasubramanian K, Venkatraman B. Dicentric assay: inter-laboratory comparison in Indian laboratories for routine and triage applications. Appl Radiat Isot 2015; 99:77-85. [PMID: 25728004 DOI: 10.1016/j.apradiso.2015.02.015] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2014] [Revised: 02/17/2015] [Accepted: 02/18/2015] [Indexed: 11/16/2022]
Abstract
An Inter-Laboratory Comparison (ILC) study on Dicentric Chromosome Assay (DCA) was carried out between two Indian biodosimetry labs. Human peripheral blood samples exposed to 10 different doses of X-rays up to 5Gy were shared between the labs to generate calibration data. Validation of calibration curves was done by dose estimation of coded samples exposed to X- or gamma radiation. Reliability of the DCA data for triage application was evaluated by scoring 20, 50 and 100 metaphases in the dose range of 0.5-3.0Gy. No significant difference was observed between labs regarding the established calibration data as well as the DCA triage dose assessments. Scoring of 20 metaphases (MP) was adequate to detect radiation exposure of >2Gy whereas 50 MP were sufficient to determine exposures of 0.5Gy. Both labs performed the DCA in a reliable manner and made the first step in setting up a biodosimetry network in India.
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Affiliation(s)
- D Bakkiam
- Radiological Safety Division, Indira Gandhi Center for Atomic Research, Kalpakkam, Tamilnadu, India
| | - M Bhavani
- Sri Ramachandra University, Porur, Chennai 600116, Tamilnadu, India
| | - A Arul Anantha Kumar
- Radiological Safety Division, Indira Gandhi Center for Atomic Research, Kalpakkam, Tamilnadu, India.
| | - Swetha Sonwani
- Radiological Safety Division, Indira Gandhi Center for Atomic Research, Kalpakkam, Tamilnadu, India
| | - P Venkatachalam
- Sri Ramachandra University, Porur, Chennai 600116, Tamilnadu, India
| | - K Sivasubramanian
- Radiological Safety Division, Indira Gandhi Center for Atomic Research, Kalpakkam, Tamilnadu, India
| | - B Venkatraman
- Radiological Safety Division, Indira Gandhi Center for Atomic Research, Kalpakkam, Tamilnadu, India
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Bhavani M, Tamizh Selvan G, Kaur H, Adhikari JS, Vijayalakshmi J, Venkatachalam P, Chaudhury NK. Dicentric chromosome aberration analysis using giemsa and centromere specific fluorescence in-situ hybridization for biological dosimetry: An inter- and intra-laboratory comparison in Indian laboratories. Appl Radiat Isot 2014; 92:85-90. [PMID: 25014548 DOI: 10.1016/j.apradiso.2014.06.004] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2014] [Revised: 05/19/2014] [Accepted: 06/04/2014] [Indexed: 11/25/2022]
Abstract
To facilitate efficient handling of large samples, an attempt towards networking of laboratories in India for biological dosimetry was carried out. Human peripheral blood samples were exposed to (60)Co γ-radiation for ten different doses (0-5Gy) at a dose rate of 0.7 and 2Gy/min. The chromosomal aberrations (CA) were scored in Giemsa-stained and fluorescence in-situ hybridization with centromere-specific probes. No significant difference (p>0.05) was observed in the CA yield for given doses except 4 and 5Gy, between the laboratories, among the scorers and also staining methods adapted suggest the reliability and validates the inter-lab comparisons exercise for triage applications.
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Affiliation(s)
- M Bhavani
- Department of Human Genetics, College of Biomedical Sciences Technology and Research, Sri Ramachandra University, Porur, Chennai 600116, Tamil Nadu, India.
| | - G Tamizh Selvan
- Department of Human Genetics, College of Biomedical Sciences Technology and Research, Sri Ramachandra University, Porur, Chennai 600116, Tamil Nadu, India; Chemical Radioprotector and Radiation Dosimetry Research Group, Institute of Nuclear Medicine and Allied Sciences, Brig Mazumdar Road, DRDO, Timarpur, New Delhi 110054, India.
| | - Harpreet Kaur
- Department of Human Genetics, College of Biomedical Sciences Technology and Research, Sri Ramachandra University, Porur, Chennai 600116, Tamil Nadu, India.
| | - J S Adhikari
- Chemical Radioprotector and Radiation Dosimetry Research Group, Institute of Nuclear Medicine and Allied Sciences, Brig Mazumdar Road, DRDO, Timarpur, New Delhi 110054, India.
| | - J Vijayalakshmi
- Department of Human Genetics, College of Biomedical Sciences Technology and Research, Sri Ramachandra University, Porur, Chennai 600116, Tamil Nadu, India.
| | - P Venkatachalam
- Department of Human Genetics, College of Biomedical Sciences Technology and Research, Sri Ramachandra University, Porur, Chennai 600116, Tamil Nadu, India.
| | - N K Chaudhury
- Chemical Radioprotector and Radiation Dosimetry Research Group, Institute of Nuclear Medicine and Allied Sciences, Brig Mazumdar Road, DRDO, Timarpur, New Delhi 110054, India.
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18
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Ainsbury EA, Vinnikov VA, Maznyk NA, Lloyd DC, Rothkamm K. A comparison of six statistical distributions for analysis of chromosome aberration data for radiation biodosimetry. RADIATION PROTECTION DOSIMETRY 2013; 155:253-267. [PMID: 23325781 DOI: 10.1093/rpd/ncs335] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/01/2023]
Abstract
The Poisson distribution is the most widely recognised and commonly used distribution for cytogenetic radiation biodosimetry. However, it is recognised that, due to the complexity of radiation exposure cases, other distributions may be more properly applied. Here, the Poisson, gamma, negative binomial, beta, Neyman type-A and Hermite distributions are compared in terms of their applicability to 'real-life' radiation exposure situations. The identification of the most appropriate statistical model in each particular exposure situation more correctly characterises data. The results show that for acute, homogeneous (whole-body) exposures, the Poisson distribution can still give a good fit to the data. For localised partial-body exposures, the Neyman type-A model was found to be the most robust. Overall, no single distribution was found to be universally appropriate. A distribution-specific method of analysis of cytogenetic data is therefore recommended. Such an approach may lead potentially to more accurate biological dose estimates.
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Affiliation(s)
- Elizabeth A Ainsbury
- Health Protection Agency Centre for Radiation, Chemical and Environmental Hazards, Chilton, Didcot, Oxon OX11 0RQ, UK.
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Vinnikov VA, Maznyk NA. Cytogenetic dose-response in vitro for biological dosimetry after exposure to high doses of gamma-rays. RADIATION PROTECTION DOSIMETRY 2013; 154:186-197. [PMID: 22923248 DOI: 10.1093/rpd/ncs200] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/01/2023]
Abstract
The dose response for dicentrics plus centric rings and total unstable chromosome-type aberrations was studied in the first mitoses of cultured human peripheral blood lymphocytes irradiated in vitro to doses of ∼2, 4, 6, 8, 10, 16 and 20 Gy of acute (60)Со gamma-rays. A dose-dependent increase of aberration yield was accompanied by a tendency to the underdispersion of dicentrics and centric rings among cells distributions compared with Poisson statistics at doses ≥6 Gy. The formal fitting of the data to a linear-quadratic model resulted in an equation with the linear and quadratic coefficients ranged 0.098-0.129×cell(-1)×Gy(-1) and 0.039-0.034×cell(-1)×Gy(-2), respectively, depending on the fitting method. The actual radiation-induced aberration yield was markedly lower than expected from a calibration curve, generated earlier within a lower dose range. Interlaboratory variations in reported dicentric yields induced by medium-to-high radiation doses in vitro are discussed.
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Affiliation(s)
- Volodymyr A Vinnikov
- Radiation Cytogenetics Laboratory, Grigoriev Institute for Medical Radiology of the National Academy of Medical Science of Ukraine, Pushkinskaya St. 82, Kharkiv 61024, Ukraine.
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Martins V, Antunes AC, Monteiro Gil O. Implementation of a dose-response curve for γ-radiation in the Portuguese population by use of the chromosomal aberration assay. Mutat Res 2012; 750:50-4. [PMID: 23043763 DOI: 10.1016/j.mrgentox.2012.09.009] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2012] [Revised: 08/07/2012] [Accepted: 09/10/2012] [Indexed: 11/27/2022]
Abstract
An in vitro dose-response curve following exposure to γ-radiation was determined at the IST/ITN, by use of the chromosomal aberration assay. This is the first study of this kind carried out among the Portuguese population. Un-irradiated and γ-irradiated peripheral blood lymphocytes from 16 healthy donors were cultured. A total of 22,395 metaphases were analyzed for frequency and distribution of dicentrics and centric rings, as a function of the radiation dose. The dose-response data for dicentrics and dicentrics plus centric rings were fitted by use of a linear-quadratic model: Y(dic)=(0.0011±0.0006)+(0.0105±0.0035)D+(0.0480±0.0019)D(2) and Y(dic+rings)=(0.0011±0.0006)+(0.0095±0.0036)D+(0.0536±0.0020)D(2). Also, calibration curves related to age and gender were determined, but no significant differences were found. Following the establishment of the dose-response curves, a validation experiment was carried out with three individuals. Real and estimated doses, obtained with the dose-response curves, were in agreement. These results give us confidence to apply both dose-response calibration curves in future biological dosimetry requirements.
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Affiliation(s)
- V Martins
- IST/ITN - Instituto Superior Técnico, Universidade Técnica de Lisboa, Estrada Nacional, Bobadela LRS, Portugal
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Maznyk NA, Wilkins RC, Carr Z, Lloyd DC. The capacity, capabilities and needs of the WHO BioDoseNet member laboratories. RADIATION PROTECTION DOSIMETRY 2012; 151:611-620. [PMID: 22908357 DOI: 10.1093/rpd/ncs156] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/01/2023]
Abstract
Biodosimetry is an essential tool for providing timely assessments of radiation exposure, particularly when physical dosimetry is unavailable or unreliable. For mass-casualty events involving public exposure to ionising radiation, it is paramount to rapidly provide this dose information for medical management of casualties. The dicentric chromosome assay is currently the most reliable accepted method for biodosimetry; however, in a mass-casualty scenario, the throughput of this assay will be challenged by its time-consuming nature and the specific expertise required. To address this limitation, many countries have established expertise in cytogenetic biodosimetry and started developing surge capabilities through setting up regional networks to deal with emergency situations. To capitalise on this growing expertise and organise it into an internationally coordinated laboratory network, the World Health Organization has created and launched a global biodosimetry network (BioDoseNet). In order to determine the existing capacity of BioDoseNet member laboratories, including their expertise and in vivo experience, involvement in national and international activities, problems, needs and prospects, an in-depth survey was conducted. These survey results provide significant information on the current state of emergency cytogenetic biodosimetry capabilities around the world.
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Affiliation(s)
- N A Maznyk
- Institute for Medical Radiology of the Academy of Medical Science of Ukraine, Pushkinskaya St. 82, Kharkiv 61024, Ukraine
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22
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Di Giorgio M, Barquinero JF, Vallerga MB, Radl A, Taja MR, Seoane A, De Luca J, Oliveira MS, Valdivia P, Lima OG, Lamadrid A, Mesa JG, Aguilera IR, Cardoso TM, Carvajal YCG, Maldonado CA, Espinoza ME, Martínez-López W, Méndez-Acuña L, Di Tomaso MV, Roy L, Lindholm C, Romm H, Güçlü I, Lloyd DC. Biological dosimetry intercomparison exercise: an evaluation of triage and routine mode results by robust methods. Radiat Res 2011; 175:638-49. [PMID: 21306200 DOI: 10.1667/rr2425.1] [Citation(s) in RCA: 43] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
Abstract
Well-defined protocols and quality management standards are indispensable for biological dosimetry laboratories. Participation in periodic proficiency testing by interlaboratory comparisons is also required. This harmonization is essential if a cooperative network is used to respond to a mass casualty event. Here we present an international intercomparison based on dicentric chromosome analysis for dose assessment performed in the framework of the IAEA Regional Latin American RLA/9/054 Project. The exercise involved 14 laboratories, 8 from Latin America and 6 from Europe. The performance of each laboratory and the reproducibility of the exercise were evaluated using robust methods described in ISO standards. The study was based on the analysis of slides from samples irradiated with 0.75 (DI) and 2.5 Gy (DII). Laboratories were required to score the frequency of dicentrics and convert them to estimated doses, using their own dose-effect curves, after the analysis of 50 or 100 cells (triage mode) and after conventional scoring of 500 cells or 100 dicentrics. In the conntional scoring, at both doses, all reported frequencies were considered as satisfactory, and two reported doses were considered as questionable. The analysis of the data dispersion among the dicentric frequencies and among doses indicated a better reproducibility for estimated doses (15.6% for DI and 8.8% for DII) than for frequencies (24.4% for DI and 11.4% for DII), expressed by the coefficient of variation. In the two triage modes, although robust analysis classified some reported frequencies or doses as unsatisfactory or questionable, all estimated doses were in agreement with the accepted error of ±0.5 Gy. However, at the DI dose and for 50 scored cells, 5 out of the 14 reported confidence intervals that included zero dose and could be interpreted as false negatives. This improved with 100 cells, where only one confidence interval included zero dose. At the DII dose, all estimations fell within ±0.5 Gy of the reference dose interval. The results obtained in this triage exercise indicated that it is better to report doses than frequencies. Overall, in both triage and conventional scoring modes, the laboratory performances were satisfactory for mutual cooperation purposes. These data reinforce the view that collaborative networking in the case of a mass casualty event can be successful.
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Affiliation(s)
- M Di Giorgio
- Autoridad Regulatoria Nuclear (ARN), Av. Del Libertador 8250, C1429BNP, Buenos Aires, Argentina.
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Pinto MMPDL, Santos NFG, Amaral A. Current status of biodosimetry based on standard cytogenetic methods. RADIATION AND ENVIRONMENTAL BIOPHYSICS 2010; 49:567-81. [PMID: 20617329 DOI: 10.1007/s00411-010-0311-3] [Citation(s) in RCA: 100] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/12/2009] [Accepted: 06/19/2010] [Indexed: 05/19/2023]
Abstract
Knowledge about dose levels in radiation protection is an important step for risk assessment. However, in most cases of real or suspected accidental exposures to ionizing radiation (IR), physical dosimetry cannot be performed for retrospective estimates. In such situations, biological dosimetry has been proposed as an alternative for investigation. Briefly, biodosimetry can be defined as individual dose evaluation based on biological endpoints induced by IR (so-called biomarkers). The relationship between biological endpoints and absorbed dose is not always straightforward: nausea, vomiting and diarrhoea, for example, are the most well-known biological effects of individual irradiation, but a precise correlation between those symptoms and absorbed dose is hardly achieved. The scoring of unstable chromosomal-type aberrations (such as dicentrics and rings) and micronuclei in mitogen-stimulated peripheral blood, up till today, has been the most extensively biodosimetry assay employed for such purposes. Dicentric assay is the gold standard in biodosimetry, since its presence is generally considered to be specific to radiation exposure; scoring of micronuclei (a kind of by-product of chromosomal damages) is easier and faster than that of dicentrics for dose assessment. In this context, the aim of this work is to present an overview on biodosimetry based on standard cytogenetic methods, highlighting its advantages and limitations as tool in monitoring of radiation workers' doses or investigation into accidental exposures. Recent advances and perspectives are also briefly presented.
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Ainsbury EA, Livingston GK, Abbott MG, Moquet JE, Hone PA, Jenkins MS, Christensen DM, Lloyd DC, Rothkamm K. Interlaboratory Variation in Scoring Dicentric Chromosomes in a Case of Partial-Body X-Ray Exposure: Implications for Biodosimetry Networking and Cytogenetic “Triage Mode” Scoring. Radiat Res 2009; 172:746-52. [DOI: 10.1667/rr1934.1] [Citation(s) in RCA: 27] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/03/2022]
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Blakely WF, Carr Z, Chu MCM, Dayal-Drager R, Fujimoto K, Hopmeir M, Kulka U, Lillis-Hearne P, Livingston GK, Lloyd DC, Maznyk N, Perez MDR, Romm H, Takashima Y, Voisin P, Wilkins RC, Yoshida MA. WHO 1st Consultation on the Development of a Global Biodosimetry Laboratories Network for Radiation Emergencies (BioDoseNet). Radiat Res 2009; 171:127-39. [DOI: 10.1667/rr1549.1] [Citation(s) in RCA: 92] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/03/2022]
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Gruel G, Voisin P, Vaurijoux A, Roch-Lefevre S, Grégoire E, Maltere P, Petat C, Gidrol X, Voisin P, Roy L. Broad modulation of gene expression in CD4+ lymphocyte subpopulations in response to low doses of ionizing radiation. Radiat Res 2008; 170:335-44. [PMID: 18763857 DOI: 10.1667/rr1147.1] [Citation(s) in RCA: 26] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2007] [Accepted: 04/17/2008] [Indexed: 11/03/2022]
Abstract
To compare the responses of the different lymphocyte subtypes after an exposure of whole blood to low doses of ionizing radiation, we examined variations in gene expression in different lymphocyte subpopulations using microarray technology. Blood samples from five healthy donors were independently exposed to 0 (sham irradiation), 0.05 and 0.5 Gy of ionizing radiation. Three and 24 h after exposure, CD56+, CD4+ and CD8+ cells were negatively isolated. RNA from each set of experimental conditions was competitively hybridized on 25k oligonucleotide microarrays. Modifications of gene expression were measured after both intervals and in all cell types. Twenty-four hours after exposure to 0.5 Gy, we observed an induction of the expression of BAX, PCNA, GADD45, DDB2 and CDKN1A. However, the numbers of modulated genes greatly differed between cell types. In particular, 3 h after exposure to doses as low as 0.05 Gy, the number of down-modulated genes was 10 times greater for CD4+ cells than for all other cell types. Moreover, most of these repressed genes were taking part in the cell processes of protein biosynthesis and oxidative phosphorylation. The results suggest that several biological pathways in CD4+ cells could be sensitive to low doses of radiation. Therefore, specifically studying CD4+ cells could help to understand the mechanisms involved in low-dose response and allow their detection.
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Affiliation(s)
- Gaëtan Gruel
- Laboratoire de Dosimétrie Biologique, Institut de Radioprotection et de Sûreté Nucléaire (IRSN), 92262 Fontenay-aux-Roses, France
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Stricklin D, Wilkinson D, Arvidsson E, Prud’homme-Lalonde L, Thorleifson E, Mullins D, Lachapelle S. An initial limited biodosimetry inter-comparison exercise: FOI and DRDC Ottawa. RADIAT MEAS 2007. [DOI: 10.1016/j.radmeas.2007.05.043] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
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Lamadrid AI, García O, Delbos M, Voisin P, Roy L. PCC-ring induction in human lymphocytes exposed to gamma and neutron irradiation. JOURNAL OF RADIATION RESEARCH 2007; 48:1-6. [PMID: 17102580 DOI: 10.1269/jrr.0625] [Citation(s) in RCA: 33] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/12/2023]
Abstract
In case of an accidental overexposure to ionizing radiation where the dose received by the victim is over 5 Gy, the conventional biological indicator of dose, the dicentric assay, does not provide an accurate enough dose measurement. A more appropriate technique is to measure ring chromosomes in stimulated lymphocytes. Dose-effect relationships were obtained by plotting the frequencies of Premature Chromosome Condensation (PCC)-rings in PCC lymphocytes obtained by chemical induction with Calyculin A in vitro, irradiated with doses between 5 to 25 Gy. Cells were exposed either to neutron or to gamma rays and the corresponding dose effect curves are presented in this paper for the first time in literature. For the elaboration of these curves, 9 675 PCC cells in G1 G2 and M/A stages were analysed. The results were fitted to a lineal model in gamma irradiation up to 25 Gy. For neutron irradiation the data was fitted to a lineal model up to 10 Gy, and then dose saturation was observed. In conclusion, with this technique it is possible to set up dose effect curves up to 25 or 10 Gy according to the gamma or neutron radiation.
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Affiliation(s)
- Ana I Lamadrid
- Centro de Protección e Higiene de las Radiaciones, La Habana, Cuba
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