Volume 8, 2024

Radiobiology

EVALUATION OF THE ASSESSMENT DOSE WITH BIODOSIMETRY METHODS, APPLICABLE IN BULGARIA. USE OF DICENTRIC CHROMOSOMAL ASSAY (DCA) AND CYTOKINESIS-BLOCK MICRONUCLEUS ASSAY

Galina Racheva

Pages: 35-38

DOI: 10.21175/RadProc.2024.08

Radiation biodosimetry deals with the measurement of a biological response that serves as a surrogate for estimating the absorbed radiation dose in exposed humans. The biodosimetry methods include cytogenetic methods such as dicentric chromosomal assay (DCA), cytokinesis-block micronucleus assay (CBMN), Fluorescence in-situ hybridization (FISH) assay, Premature chromosome condensation (PCC), etc. All of them score the marking damages such dicentric chromosomes or centric rings to calculate the absorbed dose of ionizing radiation. As a part of the European union, Bulgarian radiobiology laboratories had to switch the direction of the mainly research activity to possibility for routine practice of analysis and diagnostic of the assessment dose after ionizing exposure. This possibility determines to use of more precise methods to diagnose cellular injuries accurately. For a short period of time Bulgarian laboratories had to choose method of analysis, to develop working protocols and their own calibration curves for them. The Research laboratory of Radiobiology and Radiation protection, Military Medical Academy-Sofia is in the process of integration of DCA as a main method of biodosimetry and CBMN as a supplementing method. The criteria to choose DCA as a main method is affordability and accuracy of the method. Next stage is to organize the whole process of integration as a routine diagnostic practice as additional source of information for the patients used by the clinical hematologists and oncologists. Aim of the study: The aim of the current study is to present and describe the selected biodosimetry methods, planned to be used in the Military Medical Academy-Sofia. Materials and methods:Dicentric chromosomal assay (DCA) and cytokinesis- block micronucleus assay (CBMN). Results: The review of the described methods, give the priority to the golden standard method (DCA). It is chosen as the most affordable, applicable and highly effective for the needs of the Scientific laboratory of Radiobiology and Radiation protection, Military Medical Academy-Sofia. Cytokinesis-block micronucleus assay (CBMN) is good supplementary method, but cannot be used as a main dosimetry method, because of its limitations. Conclusion: The biodosimetry assessment of the absorbed dose is a high skilled activity. It has involved team of professionals, correct selection of applicable methods and preliminary optimization of the process. Take into consideration of the advantages and disadvantages of the selected methods, the most affordable and effective method is DCA analysis.
  1. A.S. Balajee, H.C. Turner, R.C. Wilkins, “Radiation Biodosimetry: Current Status and Future Initiatives” Cytogenet. Genome Res., vol. 163, no. 3-4, pp. 85–88, 2023.
    https://doi.org/10.1159/000535488
  2. R. Havránková, “Biological effects of ionizing radiation”, Cas Lek Cesk, vol. 159. No. 7-8, pp. 258- 260, 2020.
    Retrieved from: www.europepmc.org/abstract/MED/33445930
  3. R. Mendelson, “Informed consent for stochastic effects of ionising radiation in diagnostic imaging”, Br. J. Radiol., vol. 95, no. 1132, pp. 2021126-1-3, 2022.
    https://doi.org/10.1259/bjr.20211265
  4. R. M’Kacher, B. Colicchio, C. Borie, S. Junker, V. Marquet, L. Heidingsfelder, K. Soehnlen, W. Najar, W.M. Hempel, N. Oudrhiri, et al., “Telomere and Centromere Staining Followed by M-FISH Improves Diagnosis of Chromosomal Instability and Its Clinical Utility”, Genes, vol. 1, no. 5, pp. 475-1-17, 2020
    https://doi.org/10.3390/genes11050475
  5. H. Romm, R.C. Wilkins, C.N. Coleman, et al., “Biological dosimetry by the triage dicentric chromosome assay: potential implications for treatment of acute radiation syndrome in radiological mass casualties”, Radiat. Res., vol. 175, no. 3, pp. 397- 404, 2011.
    https://doi.org/10.1667/rr2321.1
  6. H. Nobuyuki, F. Yuki, “Classification of radiation effects for dose limitation purposes: history, current situation and future prospects”, J. Radiat. Res., vol. 55, no. 4, pp. 629-640, 2014.
    https://doi.org/10.1093/jrr/rru019
  7. C. Herate, L. Sabatier, “Retrospective biodosimetry techniques: Focus on cytogenetics assays for individuals exposed to ionizing radiation”, Mutat. Res./Rev. Mutat. Res., vol. 783, 108287, 2020.
    https://doi.org/10.1016/j.mrrev.2019.108287
  8. International Atomic Energy Agency. Cytogenetic Analysis for Radiation Dose Assessment. Manual. Technical reports series, 2001, no. 405, Vienna, IAEA. Retrieved from: https://www.iaea.org/publications/6303/cytogenetic -analysis-for-radiation-dose-assessment
    Retrieved on: Sept. 24, 2024.
  9. International Organization for Standardization (ISO) Radiation protection—performance criteria for service laboratories performing biological dosimetry by cytogenetics ISO 19238, Geneva: ISO, 2014.
  10. S. Jang, J. Lee, S.H. Kim, S. Han, S.G. Shin, S. Lee, I. Kang, W.S. Jo, S. Jeong, S.J. Oh, C.G. Lee, “Radiation dose estimation with multiple artificial neural networks in dicentric chromosome assay”, Int. J. Radiat. Biol., vol. 100, no. 6, pp. 865-874, 2024.
    https://doi.org/10.1080/09553002.2024.2338531
  11. U. Oestreicher, D. Samaga, E. Ainsbury et al., “RENEB intercomparisons applying the conventional Dicentric Chromosome Assay (DCA)”, Int. J. Radiat. Biol., vol. 93, no. 1, pp. 20-29, 2017.
    https://doi.org/10.1080/09553002.2016.1233370
  12. F.N. Flegal, Y. Devantier, J.P. McNamee R.C. Wilkins, “Quick scan dicentric chromosome analysis for radiation biodosimetry”, Health Phys., vol. 98, no. 2, pp. 276-281, 2010.
    https://doi.org/10.1097/HP.0b013e3181aba9c7
  13. H. Thierens, A. Vral, “The micronucleus assay in radiation accidents”, Ann. Ist. Super Sanita, vol. 45, no. 3, pp. 260-264, 2009.
    Retrieved from: https://www.iss.it/documents/20126/45616/ANN_09_33_Thierens.pdf/16f376be-1fac-e656-3b4a- cc57c47691e7?t=1581100041525
  14. T. Rich, R.L. Allen, A.H. Wyllie, “Defying death after DNA damage”, Nature, vol. 407, pp. 777-783, 2000.
    https://doi.org/10.1038/35037717
  15. P.G. Prasanna, M. Moroni, T.C. Pellmar, “Triage dose assessment for partial-body exposure: Dicentric analysis”, Health Phys., vol. 98, no. 2, pp. 244–251, 2010.
    https://doi.org/10.1097/01.HP.0000348020.14969.4
  16. E.E. Manasanch, R.Z. Orlowski, “Proteasome inhibitors in cancer therapy”, Nat. Rev. Clin. Oncol., vol. 14, no. 7, pp. 417-433, 2017.
    https://doi.org/10.1038/nrclinonc.2016.206
  17. C. Beinke, M. Port, A. Riecke, C.G. Ruf, M. Abend, “Adaption of the Cytokinesis-Block Micronucleus Cytome Assay for Improved Triage Biodosimetry”, Radiation Research, vol. 185, no. 5, pp.461-472, 2016.
    https://doi.org/10.1667/rr14294.1
  18. M. Simonian, D. Shirasaki, V.S. Lee, D. Bervini, M. Grace, R.R.O. Loo, et al., “Proteomics identif ication of radiation-induced changes of membrane proteins in the rat model of arteriovenous malformation in pursuit of targets for brain AVM molecular therapy”, Clin. Proteomics, vol. 15, pp. 43-1-8, 2018.
    https://doi.org/10.1186/s12014-018-9217-x
  19. P. Voisin, “Standards in biological dosimetry: a requirement to perform an appropriate dose assessment”, Mutat. Res. Genet. Toxicol. Environ. Mutagen., vol. 793, pp. 115–122, 2015.
    https://doi.org/10.1016/j.mrgentox.2015.06.012
  20. K. Rothkamm, C. Beinke, H. Romm et al, “Comparison of established and emerging biodosimetry assays”, Radiat. Res., vol. 180, no. 2, pp. 111–119, 2013.
    https://doi.org/10.1667/RR3231.1
  21. B.L. Mahaney, K. Meek, S.P. Lees-Miller, “Repair of ionizing radiation-induced DNA double-strand breaks by non-homologous end-joining”, Biochem J., vol. 417, no. 3, pp. 639-650, 2009.
    https://doi.org/10.1042/BJ20080413
  22. A. Léonard, J. Rueff, G.B. Gerber, E.D. Léonard, “Usefulness and limits of biological dosimetry based on cytogenetic methods”, Radiat. Prot. Dosim., vol. 115, no. 1-4, pp. 448-454, 2005.
    https://doi.org/10.1093/rpd/nci061
  23. L.M. Odetti, E.V. Paravani, et al., “Micronucleus test in reptiles: Current and future perspectives”, Mutat. Res. Genet. Toxicol. Environ. Mutagen., vol. 897, p. 50377, 2024.
    https://doi.org/10.1016/j.mrgentox.2024.503772
  24. A. Shibai-Ogata, C. Kakinuma, T. Hioki, T. Kasahara, “Evaluation of high-throughput screening for in vitro micronucleus test using fluorescence-based cell imaging”, Mutagenesis, vol. 26, no. 6, pp. 709-719, 2011.
    https://doi.org/10.1093/mutage/ger037
  25. M. Repin, G. Garty, R.J. Garippa, D.J. Brenner, “RABiT-III: an Automated Micronucleus Assay at a Non-Specialized Biodosimetry Facility”, Radiat Res., vol. 201, no. 6, pp. 567-571, 2024.
    https://doi.org/10.1667/rade-23-00120.1
  26. A. Vral, M. Fenech, H. Thierens, “The micronucleus assay as a biological dosimeter of in vivo ionising radiation exposure”, Mutagenesis, vol. 26, no. 1, pp.11–17, 2011.
    https://doi.org/10.1093/mutage/geq078
  27. M.T. Sproull, K.A. Camphausen, G.D. Koblentz, “Biodosimetry: A Future Tool for Medical Management of Radiological Emergencies”, Health Security, vol. 15, no. 6, pp. 599-610, 2017.
    https://doi.org/10.1089/hs.2017.0050
Galina Racheva, "Evaluation of the assessment dose with biodosimetry methods, applicable in Bulgaria. Use of dicentric chromosomal assay (DCA) and cytokinesis-block micronucleus assay", RAD Conf. Proc., vol. 8, 2024, pp. 35-38; http://doi.org/10.21175/RadProc.2024.08