Application of the micronucleus assay performed by different scorers in case of large-scale radiation accidents

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Mass casualty scenarios of radiation exposure require high throughput biological dosimetry techniques for population triage, in order to rapidly identify individuals, who require clinical treatment. Accurate dose estimates can be made by biological dosimetry, to predict the acute radiation syndrome (ARS) within days after a radiation accident or a malicious act involving radiation. Timely information on dose is important for the medical management of acutely irradiated persons [1]. The aim of the study was to evaluate the usefulness of the micronuclei (MNi) scoring procedure in an experimental mode, where 500 binucleated cells were analyzed in different exposure dose ranges. Whole-body exposure was simulated in an in vitro experiment by irradiating whole blood collected from one healthy donor with 60 MeV protons and 250 keV X-rays, in the dose range of 0.3-4.0 Gy. For achieving meaningful results, sample scoring was performed by three independent persons, who followed guidelines described in detail by Fenech et al. [2, 3]. Compared results revealed no significant differences between scorers, which has important meaning in reducing the analysis time. Moreover, presented data based on 500 cells distribution, show that there are significant differences between MNi yields after 1.0 Gy exposure of blood for both protons and X-rays, implicating this experimental mode as appropriate for the distinction between high and low dose-exposed individuals, which allows early classification of exposed victims into clinically relevant subgroups.

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  • 1. Van del Kogel A. & Joiner M. (2009). Basic clinical radiobiology. United Kingdom: Hodder Education.

  • 2. Fenech M. Holland N. Chang W. P. Zeiger E. & Bonassi S. (2003). HUMN project: detailed description of the scoring criteria for the cytokinesis-block micronucleus assay using isolated human lymphocyte cultures. Mutat. Res. 534 65-75.

  • 3. IAEA. (2001). Cytogenetic analysis for radiation dose assessment. A manual. Vienna: International Atomic Energy Agency. (Technical Reports Series no. 405).

  • 4. Vral A. Fenech M. & Thierens H. (2011). The micronucleus assay as a biological dosimeter of in vivo ionising radiation exposure. Mutagenesis 26(1) 11-17.

  • 5. Bolognesi C. Ropolo M. Roggieri P. & Bruzzi P. (2014). Biological dosimetry by the micronucleus test: A validation study for the application in radiation mass casualties. Retrieved September 14 2014 from CSO database on the World Wide Web:

  • 6. Thierens H. Vral A. Vandevoorde C. Vandersickel V. de Gelder V. Romm H. Oestreicher U. Rothkamm K. Barnard S. Ainsbury E. Sommer S. Beinke C. & Wojcik A. (2014). Is a semi-automated approach indicated in the application of the automated micronucleus assay for triage purposes? Radiat. Prot. Dosim. 159(1/4) 87-94.

  • 7. Bolognesi C. Balia C. Roggieri P. Cardinale F. Bruzzi P. Sorcinelli F. Lista F. D’Amelio R. & Righi E. (2011). Micronucleus test for radiation biodosimetry in mass casualty events: Evaluation of visual and automated scoring. Radiat. Meas. 46(2) 169-175.

  • 8. Franco M. Bolognesi C. De Amicis A. Amati A. Di Cristofaro S. Regalbuto E. Ropolo M. Lista F. & De Sanctis S. (2012). Interlaboratory comparison on cytokinesis-block micronucleus assay for X-ray calibration curve and dose prediction in Italy. Effects of Ionizing Radiation Exposure and Countermeasures: Current Status and Future Perspectives S&T. In T. C. Pellmar (Ed.) Biological effects of ionizing radiation exposure and countermeasures: Current status and future perspectives (paper no. 22). NATO Science and Technology Organization. (STO-MP-HFM-223).

  • 9. Martin P. R. Berdychevski R. E. Subramanian U. Blakely W. F. & Prasanna P. G. S. (2007). Sample tracking in an automated cytogenetic Biodosimetry Laboratory for Radiation Mass Casualties. Radiat. Meas. 42(6/7) 1119-1124.

  • 10. Michalec B. Swakoń J. Sowa U. Ptaszkiewicz M. Cywicka-Jakiel T. & Olko P. (2010). Proton radiotherapy facility for ocular tumors at the IFJ PAN in Kraków Poland. Appl. Radiat. Isot. 68 738-742.

  • 11. Fenech M. Holland N. Chang W. P. Zeiger E. & Bonassi S. (1999). The Human MicroNucleus Project - An international collaborative study on the use of the micronucleus technique for measuring DNA damage in humans. Mutat. Res.-Fundam. Mol. Mech. Mutagen. 428(1/2) 271-283.

  • 12. IAEA. (2011). Cytogenetic dosimetry applications in preparedness for and response to radiation emergencies. Vienna: International Atomic Energy Agency.

  • 13. Joksic G. Pajovic S. B. Stankovic M. Pejic S. Kasapovic J. Cuttone G. Calonghi N. Masotti L. & Kanazir D. T. (2000). Chromosome aberrations micronuclei and activity of superoxide dismutases in human lymphocytes after irradiation in vitro. Cell. Mol. Life Sci. 57 842-850.

  • 14. McNamee J. P. Flegal F. N. Greene H. B. Marro L. & Wilkins R. C. (2009). Validation of the cytokinesis- -block micronucleus (CBMN) assay for use as a triage biological dosimetry tool. Radiat. Prot. Dosim. 135 232-242.

  • 15. Beinke C. Oestreicher U. Riecke A. Kulka U. Meineke V. & Romm H. (2011). Inter-laboratory comparison to validate the dicentric assay as a cytogenetic triage tool for medical management of radiation accidents. Radiat. Meas. 46 929-935.

  • 16. Wilkins R. C. Romm H. Oestreicher U. Marro L. Yoshida M. A. Suto Y. & Prasanna P. G. (2011). Biological dosimetry by the TriageDicentric Chromosome Assay - further validation of International Networking. Radiat. Meas. 46 923-928.

  • 17. Konopacka M. & Rogoliński J. (2011). Clastogenic effects in human lymphocytes exposed to low and high dose rate X-ray irradiation and vitamin C. Nukleonika 56 253-257.

  • 18. Go Y. J. Kwon O. D. Shin J. H. Kim S. H. Jeong K. S. Ryu S. Y. Park S. J. Kim C. H. Kim T. H. Lee M. H. Kim E. J. Kwak D. M. & Kang Ch. M. (2011). Dose estimation with the calibration of dose- -response curve of micronucleus in human peripheral lymphocytes induced by 50 MeV proton beams. Iran. J. Radiat. Res. Soc. 8(4) 231-236.

  • 19. Matsubara S. Ohara H. Hiroaka T. Koike S. Ando K. Yamaguchi H. Kuwabara Y. Hoshina M. & Suzuki S. (1990). Chromosome aberration frequencies produced by a 70-MeV proton beam. Radiat. Res. Soc. 123 182-191.

  • 20. Fenech M. (1998). Important variables that infl uence base-line micronucleus frequency in cytokinesis- -blocked lymphocytes - a biomarker for DNA damage in human populations. Mutat. Res. 404 155-165.

  • 21. Fenech M. (2000). The in vitro micronucleus technique. Mutat. Res. 455 81-95.

  • 22. Pajic J. Rakic B. Jovicic D. & Milovanovic A. (2014). Construction of dose response calibration curves for dicentrics and micronuclei for X radiation in a Serbian population. Mutat. Res. 773 23-28.

  • 23. Pagenetti H. Niemierko A. Ancukiewicz M. Gerweck L. E. Gotein M. Loeffl er J. S. & Suit H. D. (2002). Relative biological effectiveness (RBE) values for proton beam therapy. Int. J. Radiat. Oncol. Biol. Phys. 53(2) 407-421.

  • 24. Girdhani S. Sachs R. & Hlatky L. (2013). Biological effects of proton radiation: what we know and don’t know. Radiat. Res. Soc. 179 257-272. Retrieved September 14 2014 from PubMed database on the World Wide Web: PMID: 23373900.

  • 25. Tamizh Selvan G. Bhavani M. Vijayalakshmi J. Solomon P. F. D. & Chaudhury N. K. (2014). Delayed mitogenic stimulation decreases DNA damage assessed by micronucleus assay in human peripheral blood lymphocytes after 60-Co irradiation. Dose- Response 12(3) 498-508.

  • 26. Sullivan J. M. Prasanna P. G. Grace M. B. Wathen L. K. Koerner J. F. & Coleman C. N. (2013). Assessment of biodosimetry methods for a mass-casualty radiological incident: Medical response and management considerations. Health Phys. 105(6) 540-554. DOI: 10.1097/HP.0b013e31829cf221.

  • 27. Demidenko E. Williams B. B. & Swartz H. M. (2009). Radiation dose prediction using data on time to emesis in the case of nuclear terrorism. Radiat. Res. 171 310-319.

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