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  • 1. Ainsbury, Elizabeth A.
    et al.
    Al-hafidh, Jenna
    Bajinskis, Ainars
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Barnard, Stephen
    Barquinero, Joan Francesc
    Beinke, Christina
    de Gelder, Virginie
    Gregoire, Eric
    Jaworska, Alicja
    Lindholm, Carita
    Lloyd, David
    Moquet, Jayne
    Nylund, Reetta
    Oestreicher, Ursula
    Roch-Lefevre, Sandrine
    Rothkamm, Kai
    Romm, Horst
    Scherthan, Harry
    Sommer, Sylwester
    Thierens, Hubert
    Vandevoorde, Charlot
    Vral, Anne
    Wojcik, Andrzej
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Inter- and intra-laboratory comparison of a multibiodosimetric approach to triage in a simulated, large scale radiation emergency2014In: International Journal of Radiation Biology, ISSN 0955-3002, E-ISSN 1362-3095, Vol. 90, no 2, p. 193-202Article in journal (Refereed)
    Abstract [en]

    Purpose: The European Union's Seventh Framework Programme-funded project 'Multi-disciplinary biodosimetric tools to manage high scale radiological casualties' (MULTIBIODOSE) has developed a multiparametric approach to radiation biodosimetry, with a particular emphasis on triage of large numbers of potentially exposed individuals following accidental exposures. In November 2012, an emergency exercise took place which tested the capabilities of the MULTIBIODOSE project partners. The exercise described here had a dual purpose: Intercomparison of (i) three biodosimetric assays, and (ii) the capabilities of the seven laboratories, with regards to provision of triage status for suspected radiation exposed individuals. Materials and methods: Three biological dosimetry tools - the dicentric, micronucleus and gamma-H2AX (the phosphorylated form of member X of histone H2A, in response to DNA double-strand breaks) foci assays - were tested, in addition to provision of the triage status results (low exposure: <1 Gy; medium exposure: 1-2 Gy; high exposure: >2 Gy) by the MULTIBIODOSE software. The exercise was run in two modes: An initial triage categorisation of samples (based on the first dose estimates for each assay received from each laboratory) followed by collation of the full set of estimated doses (all the results from all modes of each assay carried out by the participating laboratories) calculated using as many modes of operation as possible of the different assays developed during the project. Simulated acute whole body and partial body exposures were included. Results: The results of the initial triage categorisation and the full comparison of assays and methods within and between laboratories are presented here. Conclusions: The data demonstrate that the MULTIBIODOSE approach of applying multiparametric tools to radiation emergencies is valid and effective.

  • 2. Ainsbury, Elizabeth A.
    et al.
    Higueras, Manuel
    Puig, Pedro
    Einbeck, Jochen
    Samaga, Daniel
    Francesc Barquinero, Joan
    Barrios, Lleonard
    Brzozowska, Beata
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute. University of Warsaw, Poland.
    Fattibene, Paola
    Gregoire, Eric
    Jaworska, Alicja
    Lloyd, David
    Oestreicher, Ursula
    Romm, Horst
    Rothkamm, Kai
    Roy, Laurence
    Sommer, Sylwester
    Terzoudi, Georgia
    Thierens, Hubert
    Trompier, Francois
    Vral, Anne
    Woda, Clemens
    Uncertainty of fast biological radiation dose assessment for emergency response scenarios2017In: International Journal of Radiation Biology, ISSN 0955-3002, E-ISSN 1362-3095, Vol. 93, no 1, p. 127-135Article in journal (Refereed)
    Abstract [en]

    Purpose: Reliable dose estimation is an important factor in appropriate dosimetric triage categorization of exposed individuals to support radiation emergency response. Materials and methods: Following work done under the EU FP7 MULTIBIODOSE and RENEB projects, formal methods for defining uncertainties on biological dose estimates are compared using simulated and real data from recent exercises. Results: The results demonstrate that a Bayesian method of uncertainty assessment is the most appropriate, even in the absence of detailed prior information. The relative accuracy and relevance of techniques for calculating uncertainty and combining assay results to produce single dose and uncertainty estimates is further discussed. Conclusions: Finally, it is demonstrated that whatever uncertainty estimation method is employed, ignoring the uncertainty on fast dose assessments can have an important impact on rapid biodosimetric categorization.

  • 3. Ainsbury, Elizabeth
    et al.
    Badie, Christophe
    Barnard, Stephen
    Manning, Grainne
    Moquet, Jayne
    Abend, Michael
    Antunes, Ana Catarina
    Barrios, Lleonard
    Bassinet, Celine
    Beinke, Christina
    Bortolin, Emanuela
    Bossin, Lily
    Bricknell, Clare
    Brzoska, Kamil
    Buraczewska, Iwona
    Huertas Castano, Carlos
    Cemusova, Zina
    Christiansson, Maria
    Mateos Cordero, Santiago
    Coster, Guillaume
    Della Monac, Sara
    Desangles, Francois
    Discher, Michael
    Dominguez, Inmaculada
    Doucha-Senf, Sven
    Eakins, Jon
    Fattibene, Paola
    Filippi, Silvia
    Frenzel, Monika
    Georgieva, Dimka
    Gregoire, Eric
    Guogyte, Kamile
    Hadjidekova, Valeria
    Hadjiiska, Ljubomira
    Hristova, Rositsa
    Karakosta, Maria
    Kis, Eniko
    Kriehuber, Ralf
    Lee, Jungil
    Lloyd, David
    Lumniczky, Katalin
    Lyng, Fiona
    Macaeva, Ellina
    Majewski, Matthaeus
    Vanda Martins, S.
    McKeever, Stephen W. S.
    Meade, Aidan
    Medipally, Dinesh
    Meschini, Roberta
    M'kacher, Radhia
    Gil, Octavia Monteiro
    Montero, Alegria
    Moreno, Mercedes
    Noditi, Mihaela
    Oestreicher, Ursula
    Oskamp, Dominik
    Palitti, Fabrizio
    Palma, Valentina
    Pantelias, Gabriel
    Pateux, Jerome
    Patrono, Clarice
    Pepe, Gaetano
    Port, Matthias
    Jesus Prieto, Maria
    Quattrini, Maria Cristina
    Quintens, Roel
    Ricoul, Michelle
    Roy, Laurence
    Sabatier, Laure
    Sebastia, Natividad
    Sholom, Sergey
    Sommer, Sylwester
    Staynova, Albena
    Strunz, Sonja
    Terzoudi, Georgia
    Testa, Antonella
    Trompier, Francois
    Valente, Marco
    Van Hoey, Olivier
    Veronese, Ivan
    Wojcik, Andrzej
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Woda, Clemens
    Integration of new biological and physical retrospective dosimetry methods into EU emergency response plans - joint RENEB and EURADOS inter-laboratory comparisons2017In: International Journal of Radiation Biology, ISSN 0955-3002, E-ISSN 1362-3095, Vol. 93, no 1, p. 99-109Article in journal (Refereed)
    Abstract [en]

    Purpose: RENEB, 'Realising the European Network of Biodosimetry and Physical Retrospective Dosimetry,' is a network for research and emergency response mutual assistance in biodosimetry within the EU. Within this extremely active network, a number of new dosimetry methods have recently been proposed or developed. There is a requirement to test and/or validate these candidate techniques and inter-comparison exercises are a well-established method for such validation. Materials and methods: The authors present details of inter-comparisons of four such new methods: dicentric chromosome analysis including telomere and centromere staining; the gene expression assay carried out in whole blood; Raman spectroscopy on blood lymphocytes, and detection of radiation induced thermoluminescent signals in glass screens taken from mobile phones. Results: In general the results show good agreement between the laboratories and methods within the expected levels of uncertainty, and thus demonstrate that there is a lot of potential for each of the candidate techniques. Conclusions: Further work is required before the new methods can be included within the suite of reliable dosimetry methods for use by RENEB partners and others in routine and emergency response scenarios.

  • 4.
    Brehwens, Karl
    et al.
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Bajinskis, Ainars
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute. University of Latvia, Latvia.
    Haghdoost, Siamak
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Wojcik, Andrzej
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute. Jan Kochanowski University, Poland.
    Micronucleus frequencies and clonogenic cell survival in TK6 cells exposed to changing dose rates under controlled temperature conditions2014In: International Journal of Radiation Biology, ISSN 0955-3002, E-ISSN 1362-3095, Vol. 90, no 3, p. 241-247Article in journal (Refereed)
    Abstract [en]

    Purpose: In most exposure scenarios the dose rate of exposure is not constant. Despite this, very little information exists on the possible biological effects of exposing cells to radiation under the conditions of a changing dose rate. The current study highlights interesting effects following exposure under these conditions.

    Materials and methods: We constructed a new exposure facility that allows exposing cells inside an incubator and used it to irradiate human lymphoblastoid TK6 cells both after a moderate (0.48 Gy) and a high (1.1 Gy) dose, where the change in dose rate was, respectively, ≈ 17-fold change (2.2 - 37 mGy/min) and ≈ 39-fold (2.7 - 106 mGy/min). Clonogenic survival and micronuclei (MN) induction were the chosen endpoints.

    Results: The obtained results confirm the outcome of our first study that TK6 cells exposed to a decreasing dose rate express more MN than cells exposed to an increasing or constant dose rate. The effect was not seen after the moderate dose of 0.48 Gy or detectable at the level of clonogenic cell survival.

    Conclusions: We speculate that the high level of MN is probably related to a delayed elimination of damaged cells by interphase death, as opposed to mechanisms relating to DNA damage and repair.

  • 5.
    Brzozowska, Beata
    et al.
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute. University of Warsaw, Poland.
    Ainsbury, Elizabeth
    Baert, Annelot
    Beaton-Green, Lindsay
    Barrios, Leonardo
    Francesc Barquinero, Joan
    Bassinet, Celine
    Beinke, Christina
    Benedek, Anett
    Beukes, Philip
    Bortolin, Emanuela
    Buraczewska, Iwona
    Burbidge, Christopher
    De Amicis, Andrea
    De Angelis, Cinzia
    Della Monaca, Sara
    Depuydt, Julie
    De Sanctis, Stefania
    Dobos, Katalin
    Domene, Mercedes Moreno
    Dominguez, Inmaculada
    Facco, Eva
    Fattibene, Paola
    Frenzel, Monika
    Gil, Octavia Monteiro
    Gonon, Geraldine
    Gregoire, Eric
    Gruel, Gaetan
    Hadjidekova, Valeria
    Hatzi, Vasiliki I.
    Hristova, Rositsa
    Jaworska, Alicja
    Kis, Eniko
    Kowalska, Maria
    Kulka, Ulrike
    Lista, Florigio
    Lumniczky, Katalin
    Martinez-Lopez, Wilner
    Meschini, Roberta
    Moertl, Simone
    Moquet, Jayne
    Noditi, Mihaela
    Oestreicher, Ursula
    Orta Vazquez, Manuel Luis
    Palma, Valentina
    Pantelias, Gabriel
    Montoro Pastor, Alegria
    Patrono, Clarice
    Piqueret-Stephan, Laure
    Quattrini, Maria Cristina
    Regalbuto, Elisa
    Ricoul, Michelle
    Roch-Lefevre, Sandrine
    Roy, Laurence
    Sabatier, Laure
    Sarchiapone, Lucia
    Sebastia, Natividad
    Sommer, Sylwester
    Sun, Mingzhu
    Suto, Yumiko
    Terzoudi, Georgia
    Trompier, Francois
    Vral, Anne
    Wilkins, Ruth
    Zafiropoulos, Demetre
    Wieser, Albrecht
    Woda, Clemens
    Wojcik, Andrzej
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute. Jan Kochanowski University, Poland.
    RENEB accident simulation exercise2017In: International Journal of Radiation Biology, ISSN 0955-3002, E-ISSN 1362-3095, Vol. 93, no 1, p. 75-80Article in journal (Refereed)
    Abstract [en]

    Purpose: The RENEB accident exercise was carried out in order to train the RENEB participants in coordinating and managing potentially large data sets that would be generated in case of a major radiological event. Materials and methods: Each participant was offered the possibility to activate the network by sending an alerting email about a simulated radiation emergency. The same participant had to collect, compile and report capacity, triage categorization and exposure scenario results obtained from all other participants. The exercise was performed over 27 weeks and involved the network consisting of 28 institutes: 21 RENEB members, four candidates and three non-RENEB partners. Results: The duration of a single exercise never exceeded 10 days, while the response from the assisting laboratories never came later than within half a day. During each week of the exercise, around 4500 samples were reported by all service laboratories (SL) to be examined and 54 scenarios were coherently estimated by all laboratories (the standard deviation from the mean of all SL answers for a given scenario category and a set of data was not larger than 3 patient codes). Conclusions: Each participant received training in both the role of a reference laboratory (activating the network) and of a service laboratory (responding to an activation request). The procedures in the case of radiological event were successfully established and tested.

  • 6. Brzozowska, Kinga
    et al.
    Johannes, Christian
    Obe, Gunter
    Hentschel, Reinhard
    Morand, Josselin
    Moss, Ray
    Wittig, Andrea
    Sauerwein, Wolfgang
    Liniecki, Julian
    Szumiel, Irena
    Wojcik, Andrzej
    Stockholm University, Faculty of Science, Department of Genetics, Microbiology and Toxicology.
    Effect of temperature during irradiation on the level of micronuclei in human peripheral blood lymphocytes exposed to X-rays and neutrons.2009In: International Journal of Radiation Biology, ISSN 0955-3002, E-ISSN 1362-3095, p. 1-9Article in journal (Refereed)
    Abstract [en]

    Objectives: It has been reported that the level of cytogenetic damage in human peripheral blood lymphocytes (PBL) is higher following irradiation at 37 degrees C than at 0-4 degrees C. The mechanisms of this cytogenetic temperature effect are not fully known. The aim of our study was to check whether the effect was related to the indirect or direct action of radiation. Materials and methods: PBL were kept at 37 degrees C and 0 degrees C for 20 min and exposed to 2 Gy of X-rays. In some experiments PBL were isolated and 0.5 M dimethyl sulfoxide (DMSO) was added for 5 min before exposure. PBL were also irradiated at 37 degrees C and 0 degrees C with 1 Gy of 6 MeV neutrons. Micronuclei were scored as the endpoint. Following exposure to X-rays the level of initial DNA damage was also measured by the alkaline and neutral comet assay. Results: The frequency of micronuclei in cells exposed at 37 degrees C to X-rays or neutrons was higher than that after exposure at 0 degrees C. No effect of temperature was seen when PBL were exposed to X-rays in the presence of DMSO. No effect of temperature was observed on the level of DNA damage measured with the alkaline or neutral comet assay. Conclusions: The results of experiments with DMSO indicate that the temperature effect is due to the indirect action of radiation, i.e., via reactive oxygen species. However, this is not supported by the results with neutrons and the comet assay. Possible reasons for the discrepancies are discussed.

  • 7. Brzozowska, Kinga
    et al.
    Pinkawa, Michael
    Eble, Michael J.
    Muller, Wolfgang-Ullrich
    Wojcik, Andrzej
    Stockholm University, Faculty of Science, Department of Genetics, Microbiology and Toxicology.
    Kriehuber, Ralf
    Schmitz, Sabine
    In vivo versus in vitro individual radiosensitivity analysed in healthy donors and in prostate cancer patients with and without severe side effects after radiotherapy2012In: International Journal of Radiation Biology, ISSN 0955-3002, E-ISSN 1362-3095, Vol. 88, no 5, p. 405-413Article in journal (Refereed)
    Abstract [en]

    Background : A high cellular radiosensitivity may be connected with a risk for development of severe side effects after radiotherapy and indicate cancer susceptibility. Hence, a fast and robust in vitro test is desirable to identify radiosensitive individuals. Materials and methods : The study included 25 prostate cancer patients with severe side effects (S) and 25 patients without severe side effects (0) after radiotherapy as well as 23 male healthy age-matched donors. Blood samples were exposed to 0.5 Gy or 1 Gy of gamma-rays. The initial level of double-strand breaks (dsb) and repair kinetics measured by phosphorylation of histone H2A (gamma-H2AX-assay), apoptosis (Annexin V-assay) and the induction of chromatid aberrations after irradiation in the G2-phase of the cell cycle (G2-assay) were analysed. Results : A significant higher chromatid aberration yield was found in lymphocytes from prostate cancer patients when compared to healthy donors. We found no significant differences between patients S and patients 0. Conclusions : There is no obvious correlation between clinical and cellular radiosensitivity in lymphocytes of prostate cancer patients when all chosen in vitro assays are considered. Although 25% of the patients showed both severe side effects and increased radiation-induced chromosomal sensitivity, predictive value of G2-assay is doubtful.

  • 8.
    Böhlen, Till Tobias
    et al.
    Stockholm University, Faculty of Science, Department of Physics.
    Dosanjh, Manjit
    Ferrari, Alfredo
    Gudowska, Irena
    Stockholm University, Faculty of Science, Department of Physics.
    Simulations of microdosimetric quantities with the Monte Carlo code FLUKA for carbon ions at therapeutic energies2012In: International Journal of Radiation Biology, ISSN 0955-3002, E-ISSN 1362-3095, Vol. 88, no 1-2, p. 176-182Article in journal (Refereed)
    Abstract [en]

    Purpose: Microdosimetric quantities can be used to estimate the biological effectiveness of radiation fields. This study evaluates the capability of the general-purpose Monte Carlo code FLUKA to simulate microscopic patterns of energy depositions for mixed radiation fields which are created by carbon ions at therapeutic energies in phantoms. Materials and methods: Measured lineal energy spectra and linear energy transfer (LET) spectra produced by carbon ions of about 300 MeV/n at different depths in phantoms representing human tissue were chosen from published literature and were compared with results from simulations of the measurement set-ups with FLUKA. Results: Simulations of the dose-weighted lineal energy spectra yd(y) and dose-weighted LET spectra describe the main features of the respective measured spectra. All simulated frequency mean and dose mean lineal energy values are, respectively, within 21% and 11% of the measured ones. A slight underestimation of fragment fluences is notable. It is shown that the simultaneous detection of several charged fragments in the TEPC ('V effect') has considerable impact on the measured lineal energy spectra of fragments. Conclusions: Agreement between measurements and FLUKA results is encouraging and shows that FLUKA can predict microdosimetric spectra of mixed radiation fields created by therapeutic carbon ions in phantoms reasonably well.

  • 9. Chandna, Sudhir
    et al.
    Dagur, Raghubendra Singh
    Mathur, Ankit
    Natarajan, Adayapalam Tyagarajan
    Harms-Ringdahl, Mats
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Haghdoost, Siamak
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Agarose overlay selectively improves macrocolony formation and radiosensitivity assessment in primary fibroblasts2014In: International Journal of Radiation Biology, ISSN 0955-3002, E-ISSN 1362-3095, Vol. 90, no 5, p. 401-406Article in journal (Refereed)
    Abstract [en]

    Purpose: Primary fibroblasts are not suitable for in vitro macrocolony assay due to their inability to form distinct colonies. Here we present a modification of agarose overlay that yielded extensive improvement in their colony formation and assessment of radiosensitivity. Materials and methods: Macrocolony formation was assessed in primary human fibroblasts VH10 and HDFn with or without overlay using 0.5% agarose in growth medium at 24 h post-seeding. Malignant human cell lines (A549, U87) and transformed nonmalignant fibroblasts (AA8 hamster, MRC5 human) were used for comparison. Results: Agarose overlay caused significant improvement marked by early appearance (one week) of distinct colonies with high cell density and multifold higher plating efficiency than conventional macrocolony assay in VH10 and HDFn human fibroblasts. Compared to conventional assay or feeder cell supplementation, agarose overlay resulted in broader cell morphology due to improved adherence, and yielded more compact colonies. Gamma-radiation dose-response survival curves could be successfully generated for both fibroblast cell lines using this method, which yielded no such effects in the transformed/malignant cell lines tested. Conclusion: This easy and inexpensive 'agarose overlay technique' significantly and selectively improves the fibroblast plating efficiency, thus considerably reducing time and effort to greatly benefit the survival studies on primary fibroblasts.

  • 10.
    Dang, Li
    et al.
    Stockholm University, Faculty of Science, Department of Genetics, Microbiology and Toxicology.
    Lisowska, Halina
    Shakeri Manesh, Sara
    Stockholm University, Faculty of Science, Department of Genetics, Microbiology and Toxicology.
    Sollazzo, Alice
    Stockholm University, Faculty of Science, Department of Genetics, Microbiology and Toxicology.
    Deperas-Kaminska, Marta
    Stockholm University, Faculty of Science, Department of Genetics, Microbiology and Toxicology. Jan Kochanowski University, Poland.
    Staaf, Elina
    Stockholm University, Faculty of Science, Department of Genetics, Microbiology and Toxicology.
    Haghdoost, Siamak
    Stockholm University, Faculty of Science, Department of Genetics, Microbiology and Toxicology.
    Brehwens, Karl
    Stockholm University, Faculty of Science, Department of Genetics, Microbiology and Toxicology.
    Wojcik, Andrzej
    Stockholm University, Faculty of Science, Department of Genetics, Microbiology and Toxicology. Jan Kochanowski University, Poland.
    Radioprotective effect of hypothermia on cells - a multiparametric approach to delineate the mechanisms2012In: International Journal of Radiation Biology, ISSN 0955-3002, E-ISSN 1362-3095, Vol. 88, no 7, p. 507-514Article in journal (Refereed)
    Abstract [en]

    Purpose: Low temperature (hypothermia) during irradiation of cells has been reported to have a radioprotective effect. The mechanisms are not fully understood. This study further investigates the possible mechanisms behind hypothermia-mediated radioprotection. Materials and methods: Human lymphoblastoid TK6 cells were incubated for 20 min at 0.8 or 37 degrees C and subsequently exposed to 1 Gy of gamma- or X-rays. The influence of ataxia telangiectasia mutated (ATM)-mediated double-strand break signalling and histone deacetylase-dependent chromatin condensation was investigated using the micronucleus assay. Furthermore, the effect of hypothermia was investigated at the level of phosphorylated histone 2AX (gamma H2AX) foci, clonogenic cell survival and micronuclei in sequentially-harvested cells. Results: The radioprotective effect of hypothermia (called the temperature effect [TE]) was evident only at the level of micronuclei at a single fixation time, was not influenced by the inhibition of ATM kinase activity and completely abolished by the histone deacetylase inhibition. No TE was seen at the level of gamma H2AX foci and cell survival. Conclusions: We suggest that low temperature during irradiation can induce a temporary cell cycle shift, which could lead to a reduced micronucleus frequency. Future experiments focused on cell cycle progression are needed to confirm this hypothesis.

  • 11. Deperas-Kaminska, Marta
    et al.
    Zaytseva, Ekaterina M.
    Deperas-Standylo, Joanna
    Mitsyn, Gennady V.
    Molokanov, Alexander G.
    Timoshenko, Gennady N.
    Wojcik, Andrzej
    Stockholm University, Faculty of Science, Department of Genetics, Microbiology and Toxicology.
    Inter-chromosomal variation in aberration frequencies in human lymphocytes exposed to charged particles of LET between 0.5 and 55 keV/mu m2010In: International Journal of Radiation Biology, ISSN 0955-3002, E-ISSN 1362-3095, Vol. 86, no 11, p. 975-985Article in journal (Refereed)
    Abstract [en]

    Purpose: To investigate the distribution of chromosomal aberrations in chromosomes 2, 8 and 14 induced by charged particles, using the fluorescence in situ hybridisation (FISH) technique. Methods: Irradiation of peripheral blood from six healthy volunteers (four male and two female) was performed at the accelerators of the Joint Institute for Nuclear Research (JINR) in Dubna (Russia). Whole blood samples were irradiated with 2 and 3 Gy of protons (170 MeV/nucleon (n), linear energy transfer (LET) approximate to 0.5 keV/mu m), 3.5 Gy of C-12 ions (480 MeV/n, LET = 10.6 keV/mu m), 3 Gy of C-12 ions 500 MeV/n, LET = 12 keV/mu m), 4 Gy of Li-7 ions (30 MeV/n, LET approximate to 20 keV/mu m) and 3 Gy of B-11 ions (32 MeV/n, LET approximate to 55 keV/mu m). Chromosomal aberrations were analysed in metaphase and prematurely condensed chromosomes (PCC) induced in G(2)-cells using calyculin A. Chromosomes 2, 8 and 14 were painted in different colours and aberrations scored with the help of an image-analysis system. Results: Chromosome 2 was generally less sensitive than expected on the basis of its DNA content. A higher than expected frequency of exchanges was found in chromosomes 8 and 14. On average, the dicentric frequency in chromosome 2 was higher than the translocation frequency, whereas variable dicentric to translocation ratios were observed in chromosomes 8 and 14. When aberrations in all painted chromosomes were summed up the ratio was close to 1. The frequency of complex aberrations correlated with LET. Conclusion: In lymphocytes of donors studied in this work chromosome 2 appears to be consistently less sensitive to protons and heavy ions than chromosomes 8 and 14. Complex aberrations appear to be a potential marker of radiation quality.

  • 12. Depuydt, Julie
    et al.
    Baeyens, Ans
    Barnard, Stephen
    Beinke, Christina
    Benedek, Anett
    Beukes, Philip
    Buraczewska, Iwona
    Darroudi, Firouz
    De Sanctis, Stefania
    Domingue, Inmaculada
    Gil, Octavia Monteiro
    Hadjidekova, Valeria
    Kis, Eniko
    Kulka, Ulrike
    Lista, Florigio
    Lumniczky, Katalin
    M'kacher, Radhia
    Moquet, Jayne
    Obreja, Doina
    Oestreicher, Ursula
    Pajic, Jelena
    Pastor, Nuria
    Popova, Ljubomira
    Regalbuto, Elisa
    Ricoul, Michelle
    Sabatier, Laure
    Slabbert, Jacobus
    Sommer, Sylwester
    Testa, Antonella
    Thierens, Hubert
    Wojcik, Andrzej
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Vral, Anne
    RENEB intercomparison exercises analyzing micronuclei (Cytokinesis-block Micronucleus Assay)2017In: International Journal of Radiation Biology, ISSN 0955-3002, E-ISSN 1362-3095, Vol. 93, no 1, p. 36-47Article in journal (Refereed)
    Abstract [en]

    Purpose: In the framework of the 'Realizing the European Network of Biodosimetry' (RENEB) project, two intercomparison exercises were conducted to assess the suitability of an optimized version of the cytokinesis-block micronucleus assay, and to evaluate the capacity of a large laboratory network performing biodosimetry for radiation emergency triages. Twelve European institutions participated in the first exercise, and four non-RENEB labs were added in the second one. Materials and methods: Irradiated blood samples were shipped to participating labs, whose task was to culture these samples and provide a blind dose estimate. Micronucleus analysis was performed by automated, semi-automated and manual procedures. Results: The dose estimates provided by network laboratories were in good agreement with true administered doses. The most accurate estimates were reported for low dose points (<= 0.94 Gy). For higher dose points (>= 2.7 Gy) a larger variation in estimates was observed, though in the second exercise the number of acceptable estimates increased satisfactorily. Higher accuracy was achieved with the semi-automated method. Conclusion: The results of the two exercises performed by our network demonstrate that the micronucleus assay is a useful tool for large-scale radiation emergencies, and can be successfully implemented within a large network of laboratories.

  • 13. Francesc Barquinero, Joan
    et al.
    Beinke, Christina
    Borras, Mireia
    Buraczewska, Iwona
    Darroudi, Firouz
    Gregoire, Eric
    Hristova, Rositsa
    Kulka, Ulrike
    Lindholm, Carita
    Moreno, Mercedes
    Moquet, Jayne
    Oestreicher, Ursula
    Jesus Prieto, M.
    Pujol, Monica
    Ricoul, Michelle
    Sabatier, Laure
    Sommer, Sylwester
    Sun, Mingzhu
    Wojcik, Andrzej
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Barrios, Leonardo
    RENEB biodosimetry intercomparison analyzing translocations by FISH2017In: International Journal of Radiation Biology, ISSN 0955-3002, E-ISSN 1362-3095, Vol. 93, no 1, p. 30-35Article in journal (Refereed)
    Abstract [en]

    Purpose: In the framework of RENEB, several biodosimetry exercises were conducted analyzing different endpoints. Among them, the analysis of translocations is considered the most useful method for retrospective biodosimetry due to the relative stability of their frequency with post irradiation time. The aim of this study was to harmonize the accuracy of translocation-based biodosimetry within the RENEB consortium. Materials and methods: An initial telescoring exercise analyzing FISH metaphase images was done to harmonize chromosome aberration descriptions. Then two blind intercomparison exercises (IE) were performed, by sending irradiated blood samples to each partner. Samples were cultured and stained by each partner using their standard protocol and translocation frequency was used to produce dose estimates. Results: The coefficient of variation in the 1st IE (CV = 0.34) was higher than in the 2nd IE (CV = 0.16 and 0.23 in the two samples analyzed), for the genomic frequency of total translocations. Z-score analysis revealed that eight out of 10 and 17 out of 20 dose estimates were satisfactory in the 1st and 2nd IE, respectively. Conclusions: The results obtained indicate that, despite the problems identified in few partners, which can be corrected, the RENEB consortium is able to carry out retrospective biodosimetry analyzing the frequency of translocations by FISH.

  • 14. Kulka, Ulrike
    et al.
    Abend, Michael
    Ainsbury, Elizabeth
    Badie, Christophe
    Francesc Barquinero, Joan
    Barrios, Lleonard
    Beinke, Christina
    Bortolin, Emanuela
    Cucu, Alexandra
    De Amicis, Andrea
    Dominguez, Inmaculada
    Fattibene, Paola
    Frovig, Anne Marie
    Gregoire, Eric
    Guogyte, Kamile
    Hadjidekova, Valeria
    Jaworska, Alicja
    Kriehuber, Ralf
    Lindholm, Carita
    Lloyd, David
    Lumniczky, Katalin
    Lyng, Fiona
    Meschini, Roberta
    Moertl, Simone
    Della Monaca, Sara
    Gil, Octavia Monteiro
    Montoro, Alegria
    Moquet, Jayne
    Moren, Mercedes
    Oestreicher, Ursula
    Palitti, Fabrizio
    Pantelias, Gabriel
    Patrono, Clarice
    Piqueret-Stephan, Laure
    Port, Matthias
    Jesus Prieto, Maria
    Quintens, Roel
    Ricoul, Michelle
    Romm, Horst
    Roy, Laurence
    Safrany, Geza
    Sabatier, Laure
    Sebastia, Natividad
    Sommer, Sylwester
    Terzoudi, Georgia
    Testa, Antonella
    Thierens, Hubert
    Turai, Istvan
    Trompier, Francois
    Valente, Marco
    Vaz, Pedro
    Voisin, Philippe
    Vral, Anne
    Woda, Clemens
    Zafiropoulos, Demetre
    Wojcik, Andrzej
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    RENEB - Running the European Network of biological dosimetry and physical retrospective dosimetry2017In: International Journal of Radiation Biology, ISSN 0955-3002, E-ISSN 1362-3095, Vol. 93, no 1, p. 2-14Article in journal (Refereed)
    Abstract [en]

    Purpose: A European network was initiated in 2012 by 23 partners from 16 European countries with the aim to significantly increase individualized dose reconstruction in case of large-scale radiological emergency scenarios. Results: The network was built on three complementary pillars: (1) an operational basis with seven biological and physical dosimetric assays in ready-to-use mode, (2) a basis for education, training and quality assurance, and (3) a basis for further network development regarding new techniques and members. Techniques for individual dose estimation based on biological samples and/or inert personalized devices as mobile phones or smart phones were optimized to support rapid categorization of many potential victims according to the received dose to the blood or personal devices. Communication and cross-border collaboration were also standardized. To assure long-term sustainability of the network, cooperation with national and international emergency preparedness organizations was initiated and links to radiation protection and research platforms have been developed. A legal framework, based on a Memorandum of Understanding, was established and signed by 27 organizations by the end of 2015. Conclusions: RENEB is a European Network of biological and physical-retrospective dosimetry, with the capacity and capability to perform large-scale rapid individualized dose estimation. Specialized to handle large numbers of samples, RENEB is able to contribute to radiological emergency preparedness and wider large-scale research projects.

  • 15.
    Liamsuwan, Thiansin
    et al.
    Karolinska Institutet, Institutionen för onkologi-patologi .
    Nikjoo, Hooshang
    Karolinska Institutet, Institutionen för onkologi-patologi.
    An energy-loss model for low- and intermediate-energy carbon projectiles in water2012In: International Journal of Radiation Biology, ISSN 0955-3002, E-ISSN 1362-3095, Vol. 88, no 1-2, p. 45-49Article in journal (Refereed)
    Abstract [en]

    Purpose: To model interaction cross sections and energy loss for carbon projectiles C(0)-C(6+) of 1-10(4) keV/u (u: atomic mass unit) in water. Materials and methods: The classical trajectory Monte Carlo method was used to calculate the ionisation and charge-transfer cross sections. The excitation cross sections were scaled from proton data using equilibrium charges determined from the charge-transfer cross sections. Energy loss was obtained from the singly differential cross sections, and ionisation potentials of the target and projectile. Results: The calculated total ionisation cross sections are consistent with measured data, while the calculated electron-capture cross sections are larger than experimental data by a factor of 3. By scaling the latter to the measured data, the cross sections were made consistent with these data for 1-10 keV/u energies. The present stopping cross sections agree well with experimental data below 10 keV/u, and with other model calculations above 2 MeV/u. Deviation from the latter is found where electron capture is competitive with ionisation, and also arises from different energy-transfer calculations. Conclusions: In this paper we report our efforts in the developments of full slowing-down Monte Carlo track structure calculations for carbon ions. Further development and refinement of the model are currently underway.

  • 16.
    Liamsuwan, Thiansin
    et al.
    Karolinska Institutet, Institutionen för onkologi-patologi .
    Uehara, Shuzo
    Kyushu University, School of Health Science.
    Emfietzoglou, Dimitris
    University of Ioannina, Medical Physics Lab.
    Nikjoo, Hooshang
    Karolinska Institutet, Institutionen för onkologi-patologi .
    A model of carbon ion interactions in water using the classical trajectory Monte Carlo method2011In: International Journal of Radiation Biology, ISSN 0955-3002, E-ISSN 1362-3095, Vol. 143, no 2-4, p. 152-155Article in journal (Refereed)
    Abstract [en]

    In this paper, model calculations for interactions of C6+ of energies from 1 keV u−1 to 1 MeV u−1 in water are presented. The calculations were carried out using the classical trajectory Monte Carlo method, taking into account the dynamic screening of the target core. The total cross sections (TCS) for electron capture and ionisation, and the singly and doubly differential cross sections (SDCS and DDCS) for ionisation were calculated for the five potential energy levels of the water molecule. The peaks in the DDCS for the electron capture to continuum and for the binary-encounter collision were obtained for 500-keV u−1 carbon ions. The calculated SDCS agree reasonably well with the z2 scaled proton data for 500 keV u−1 and 1 MeV u−1 projectiles, but a large deviation of up to 8-folds was observed for 100-keV u−1 projectiles. The TCS for ionisation are in agreement with the values calculated from the first born approximation (FBA) at the highest energy region investigated, but become smaller than the values from the FBA at the lower-energy region.                

  • 17.
    Liamsuwan, Thiansin
    et al.
    Karolinska Institutet, Institutionen för onkologi-patologi .
    Uehara, Shuzo
    Kyushu University, School of Health Science.
    Emfietzoglou, Dimitris
    University of Ioannina, Medical Physics Lab.
    Nikjoo, Hooshang
    Karolinska Institutet, Institutionen för onkologi-patologi .
    Physical and biophysical properties of proton tracks of energies 1 keV to 300 MeV in water2011In: International Journal of Radiation Biology, ISSN 0955-3002, E-ISSN 1362-3095, Vol. 87, no 2, p. 141-160Article in journal (Refereed)
    Abstract [en]

    Materials and methods: aEuro integral We present model calculations for cross sections and methods for simulations of full-slowing-down proton tracks. Protons and electrons were followed interaction-by-interaction to cut-off energies, considering elastic scattering, ionisation, excitation, and charge-transfer. Results: aEuro integral Model calculations are presented for singly differential and total cross sections, and path lengths and stopping powers as a measure of the code evaluation. Depth-dose distributions for 160 MeV protons are compared with experimental data. Frequencies of energy loss by electron interactions increase from similar to 3%% for 10 keV to similar to 77%% for 300 MeV protons, and electrons deposit aEuroS > 70%% of the dose in 160 MeV tracks. From microdosimetry calculations, 1 MeV protons were found to be more effective than 5--300 MeV in energy depositions greater than 25, 50, and 500 eV in cylinders of diameters and lengths 2, 10, and 100 nm, respectively. For lower-energy depositions, higher-energy protons are more effective. Decreasing the target size leads to the reduction of frequency- and dose-mean lineal energies for protons < 1 MeV, and conversely for higher-energy protons. Conclusions: aEuro integral Descriptions of proton tracks at molecular levels facilitate investigations of track properties, energy loss, and microdosimetric parameters for radiation biophysics, radiation therapy, and space radiation research.

  • 18.
    Liljequist, David
    Stockholm University, Faculty of Science, Department of Physics.
    A model calculation of coherence effects in the elastic backscattering of very low energy electrons (1 - 20 eV) from amorphous ice2012In: International Journal of Radiation Biology, ISSN 0955-3002, E-ISSN 1362-3095, Vol. 88, no 1-2, p. 50-53Article in journal (Refereed)
    Abstract [en]

    Purpose: Backscattering of very low energy electrons in thin layers of amorphous ice is known to provide experimental data for the elastic and inelastic cross sections and indicates values to be expected in liquid water. The extraction of cross sections was based on a transport analysis consistent with Monte Carlo simulation of electron trajectories. However, at electron energies below 20 eV, quantum coherence effects may be important and trajectory-based methods may be in significant error. This possibility is here investigated by calculating quantum multiple elastic scattering of electrons in a simple model of a very small, thin foil of amorphous ice.

    Method: The average quantum multiple elastic scattering of electrons is calculated for a large number of simulated foils, using a point-scatterer model for the water molecule and taking inelastic absorption into account. The calculation is compared with a corresponding trajectory simulation.

    Results: The difference between average quantum scattering and trajectory simulation at energies below about 20 eV is large, in particular in the forward scattering direction, and is found to be almost entirely due to coherence effects associated with the short-range order in the amorphous ice. For electrons backscattered at the experimental detection angle (45° relative to the surface normal) the difference is however small except at electron energies below about 10 eV.

    Conclusion: Although coherence effects are in general found to be strong, the mean free path values derived by trajectory-based analysis may actually be in fair agreement with the result of an analysis based on quantum scattering, at least for electron energies

  • 19. Lisowska, Halina
    et al.
    Brehwens, Karl
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Zoelzer, Friedo
    Wegierek-Ciuk, Aneta
    Czub, Joanna
    Lankoff, Anna
    Haghdoost, Siamak
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Wojcik, Andrzej
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute. Jan Kochanowski University, Poland.
    Effect of hypothermia on radiation-induced micronuclei and delay of cell cycle progression in TK6 cells2014In: International Journal of Radiation Biology, ISSN 0955-3002, E-ISSN 1362-3095, Vol. 90, no 4, p. 318-324Article in journal (Refereed)
    Abstract [en]

    Purpose: Low temperature (hypothermia) during irradiation leads to a reduced frequency of micronuclei in TK6 cells and it has been suggested that perturbation of cell cycle progression is responsible for this effect. The aim of the study was to test this hypothesis. Materials and methods: Human lymphoblastoid TK6 cells were treated by a combination of hypothermia (0.8 degrees C) and ionizing radiation in varying order (hypothermia before, during or after irradiation) and micronuclei were scored. Growth assay and two-dimensional flow cytometry was used to analyze cell cycle kinetics following irradiated of cells at 0.8 degrees C or 37.0 degrees C. Results: The temperature effect was observed at the level of micronuclei regardless of whether cells were cooled during or immediately before or after the radiation exposure. No indication of cell cycle perturbation by combined exposure to hypothermia and radiation could be detected. Conclusions: The protective effect of hypothermia observed at the level of cytogenetic damage was not due to a modulation of cell cycle progression. A possible alternative mechanism and experiments to test it are discussed.

  • 20. Lisowska, Halina
    et al.
    Wegierek-Ciuk, Aneta
    Banasik-Nowak, Anna
    Braziewicz, Janusz
    Wojewodzka, Maria
    Wojcik, Andrzej
    Stockholm University, Faculty of Science, Department of Genetics, Microbiology and Toxicology.
    Lankoff, Anna
    The dose-response relationship for dicentric chromosomes and gamma-H2AX foci in human peripheral blood lymphocytes:  Influence of temperature during exposure and intra- and inter-individual variability of donors2013In: International Journal of Radiation Biology, ISSN 0955-3002, E-ISSN 1362-3095, Vol. 89, no 3, p. 191-199Article in journal (Refereed)
    Abstract [en]

    Purpose : Hypothermia during in vitro irradiation of human peripheral blood lymphocytes (PBL) affects the level of chromosome aberrations. The molecular mechanisms of this phenomenon are not fully understood. The aim of our study was to examine the effect of hypothermia on the dose-response relationship for dicentric chromosomes and the level of gamma-H2AX (phosphorylated histone H2AX) foci. In addition, the inter- and intra-individual variability was assessed in relation to temperature. Materials and methods : PBL were kept at 0.8, 20 and 37 degrees C and then exposed to gamma-rays (from 0-3 Gy). Dicentric chromosomes were scored in first post-treatment mitoses. gamma H2AX foci were scored 15, 30, 60, 120 min and 24 h post irradiation. Results : Our results revealed that the frequency of dicentric chromosomes in cells exposed at 37 degrees C to gamma-rays was higher than after exposure at 0.8 and 20 degrees C. No effect of temperature was observed on the number of gamma-H2AX foci as well as on the intra-and inter-individual variations of the dicentric yield and the number of gamma-H2AX foci. Conclusions : Temperature at exposure to ionizing radiation has a pronounced effect on the level of cytogenetic damage but not gamma-H2AX foci.

  • 21.
    Markova, Eva
    et al.
    Stockholm University, Faculty of Science, Department of Genetics, Microbiology and Toxicology.
    Torudd, Jesper
    Stockholm University, Faculty of Science, Department of Genetics, Microbiology and Toxicology.
    Belyaev, Igor
    Stockholm University, Faculty of Science, Department of Genetics, Microbiology and Toxicology.
    Long time persistence of residual 53BP1/gamma-H2AX foci in human lymphocytes in relationship to apoptosis, chromatin condensation and biological dosimetry2011In: International Journal of Radiation Biology, ISSN 0955-3002, E-ISSN 1362-3095, Vol. 87, no 7, p. 736-745Article in journal (Refereed)
    Abstract [en]

    Purpose: Novel assay for radiosensitivity is based on measurements of residual DNA repair foci produced by several proteins including phosphorylated H2AX (gamma-H2AX), recombinase Rad51 (Rad51) and tumour suppressor p53 binding protein 1 (53BP1), which co-localise with radiation-induced DNA double-strand breaks (DSB). Here, we studied dose-response for residual 53BP1, Rad51, and gamma-H2AX foci in relationship to apoptosis and chromatin condensation in human G(0)-lymphocytes. Materials and methods: Residual foci, apoptosis and condensation of chromatin were studied following irradiation with gamma-rays at doses of 0.5-10 Gy. Results: No clear dose response for residual Rad51 was seen. Residual 53BP1/gamma-H2AX foci remained in human lymphocytes up to four weeks after irradiation. No foci formed during radiation-induced apoptosis. We provide evidence that irreversible apoptotic condensation of chromatin is responsible for arrest of residual foci and preventing de novo focus formation. Similar linear dose dependences up to 2 Gy were observed for the 53BP1/gamma-H2AX foci at all studied time points. At higher doses, saturation and decline were caused by preferential elimination of apoptotic lymphocytes with residual foci. While primary 53BP1 and gamma-H2AX foci almost completely co-localised, co-localisation of residual foci did not exceed 17%, indicating that 53BP1 and gamma-H2AX proteins may remain for different times at the locations of DSB repair. Conclusions: Prolonged persistence of residual 53BP1/gamma-H2AX foci may be used for biological dosimetry within the dose range up to 2 Gy. While foci are not formed during radiation-induced apoptosis in human lymphocytes, elimination of apoptotic cells with residual foci may affect the dose response.

  • 22. Nilsson, E. J. Charlotta
    et al.
    Jonsson, K. Ingemar
    Stockholm University, Faculty of Science, Department of Genetics, Microbiology and Toxicology.
    Pallon, Jan
    Tolerance to proton irradiation in the eutardigrade Richtersius coronifer - a nuclear microprobe study2010In: International Journal of Radiation Biology, ISSN 0955-3002, E-ISSN 1362-3095, Vol. 86, no 5, p. 420-427Article in journal (Refereed)
    Abstract [en]

    Materials and methods: Dehydrated tardigrades of the species R. coronifer were irradiated with 2.55 MeV (megaelectronvolts) protons at doses ranging from 500 gray (Gy) to 15,000 Gy, to investigate the dose-viability relationship. In addition, a focused proton microbeam was utilised to determine the areal mass distribution, using the ion beam analytical technique STIM (Scanning Transmission Ion Microscopy). Results: The experiment suggests that R. coronifer is unaffected by doses of proton irradiation up to 10,000 Gy, but shows very little viability at higher doses. The STIM analysis revealed that the thickness of the dehydrated tardigrades exceeds 150 mu m, and that a fraction of the protons may not be fully absorbed. Conclusion: Our results are in line with previous studies of exposure to high-LET radiation in tardigrades, indicating that these animals are equally or even more tolerant to high-LET compared to low-LET gamma radiation. The physiological background to this remarkable result is currently unknown, but deserves investigation.

  • 23. Oestreicher, Ursula
    et al.
    Samaga, Daniel
    Ainsbury, Elizabeth
    Antunes, Ana Catarina
    Baeyens, Ans
    Barrios, Leonardo
    Beinke, Christina
    Beukes, Philip
    Blakely, William F.
    Cucu, Alexandra
    De Amicis, Andrea
    Depuydt, Julie
    De Sanctis, Stefania
    Di Giorgio, Marina
    Dobos, Katalin
    Dominguez, Inmaculada
    Pham, Ngoc
    Espinoza, Marco E.
    Flegal, Farrah N.
    Figel, Markus
    Garcia, Omar
    Gil, Octavia Monteiro
    Gregoire, Eric
    Guerrero-Carbajal, C.
    Guclu, Inci
    Hadjidekova, Valeria
    Hande, Prakash
    Kulka, Ulrike
    Lemon, Jennifer
    Lindholm, Carita
    Lista, Florigio
    Lumniczky, Katalin
    Martinez-Lopez, Wilner
    Maznyk, Nataliya
    Meschini, Roberta
    M'kacher, Radia
    Montoro, Alegria
    Moquet, Jayne
    Moreno, Mercedes
    Noditi, Mihaela
    Pajic, Jelena
    Radl, Analia
    Ricoul, Michelle
    Romm, Horst
    Roy, Laurence
    Sabatier, Laure
    Sebastia, Natividad
    Slabbert, Jacobus
    Sommer, Sylwester
    Oliveira, Monica Stuck
    Subramanian, Uma
    Suto, Yumiko
    Tran, Que
    Testa, Antonella
    Terzoudi, Georgia
    Vral, Anne
    Wilkins, Ruth
    Yanti, LusiYanti
    Zafiropoulos, Demetre
    Wojcik, Andrzej
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    RENEB intercomparisons applying the conventional Dicentric Chromosome Assay (DCA)2017In: International Journal of Radiation Biology, ISSN 0955-3002, E-ISSN 1362-3095, Vol. 93, no 1, p. 20-29Article in journal (Refereed)
    Abstract [en]

    Purpose: Two quality controlled inter-laboratory exercises were organized within the EU project 'Realizing the European Network of Biodosimetry (RENEB)' to further optimize the dicentric chromosome assay (DCA) and to identify needs for training and harmonization activities within the RENEB network. Materials and methods: The general study design included blood shipment, sample processing, analysis of chromosome aberrations and radiation dose assessment. After manual scoring of dicentric chromosomes in different cell numbers dose estimations and corresponding 95% confidence intervals were submitted by the participants. Results: The shipment of blood samples to the partners in the European Community (EU) were performed successfully. Outside the EU unacceptable delays occurred. The results of the dose estimation demonstrate a very successful classification of the blood samples in medically relevant groups. In comparison to the 1st exercise the 2nd intercomparison showed an improvement in the accuracy of dose estimations especially for the high dose point. Conclusions: In case of a large-scale radiological incident, the pooling of ressources by networks can enhance the rapid classification of individuals in medically relevant treatment groups based on the DCA. The performance of the RENEB network as a whole has clearly benefited from harmonization processes and specific training activities for the network partners.

  • 24. Rombouts, Charlotte
    et al.
    Aerts, An
    Quintens, Roel
    Baselet, Bjorn
    El-Saghire, Hussein
    Harms-Ringdahl, Mats
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Haghdoost, Siamak
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Janssen, Ann
    Michaux, Arlette
    Yentrapalli, Ramesh
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute. Helmholtz Association, Germany.
    Benotmane, Mohammed Abderrafi
    Van Oostveldt, Patrick
    Baatout, Sarah
    Transcriptomic profiling suggests a role for IGFBP5 in premature senescence of endothelial cells after chronic low dose rate irradiation2014In: International Journal of Radiation Biology, ISSN 0955-3002, E-ISSN 1362-3095, Vol. 90, no 7, p. 560-574Article in journal (Refereed)
    Abstract [en]

    Purpose: Ionizing radiation has been recognized to increase the risk of cardiovascular diseases (CVD). However, there is no consensus concerning the dose-risk relationship for low radiation doses and a mechanistic understanding of low dose effects is needed. Material and methods: Previously, human umbilical vein endothelial cells (HUVEC) were exposed to chronic low dose rate radiation (1.4 and 4.1 mGy/h) during one, three and six weeks which resulted in premature senescence in cells exposed to 4.1 mGy/h. To gain more insight into the underlying signaling pathways, we analyzed gene expression changes in these cells using microarray technology. The obtained data were analyzed in a dual approach, combining single gene expression analysis and Gene Set Enrichment Analysis. Results: An early stress response was observed after one week of exposure to 4.1 mGy/h which was replaced by a more inflammation-related expression profile after three weeks and onwards. This early stress response may trigger the radiation-induced premature senescence previously observed in HUVEC irradiated with 4.1 mGy/h. A dedicated analysis pointed to the involvement of insulin-like growth factor binding protein 5 (IGFBP5) signaling in radiation-induced premature senescence. Conclusion: Our findings motivate further research on the shape of the dose-response and the dose rate effect for radiation-induced vascular senescence.

  • 25. Romm, Horst
    et al.
    Ainsbury, Elizabeth A.
    Francesc Barquinero, Joan
    Barrios, Leonardo
    Beinke, Christina
    Cucu, Alexandra
    Moreno Domene, Mercedes
    Filippi, Silvia
    Gil, Octavia Monteiro
    Gregoire, Eric
    Hadjidekova, Valeria
    Hatzi, Vasia
    Lindholm, Carita
    M'kacher, Radhia
    Montoro, Alegria
    Moquet, Jayne
    Noditi, Mihaela
    Oestreicher, Ursula
    Palitti, Fabrizio
    Pantelias, Gabriel
    Jesus Prieto, Maria
    Popescu, Irina
    Rothkamm, Kai
    Sebastia, Natividad
    Sommer, Sylwester
    Terzoudi, Georgia
    Testa, Antonella
    Wojcik, Andrzej
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute. Jan Kochanowski University, Poland.
    Web based scoring is useful for validation and harmonisation of scoring criteria within RENEB2017In: International Journal of Radiation Biology, ISSN 0955-3002, E-ISSN 1362-3095, Vol. 93, no 1, p. 110-117Article in journal (Refereed)
    Abstract [en]

    Purpose: To establish a training data set of digital images and to investigate the scoring criteria and dose assessment of the dicentric assay within the European network of biodosimetry (RENEB), a web based scoring inter-comparison was undertaken by 17 RENEB partners. Materials and methods: Two sets of 50 high resolution images were uploaded onto the RENEB web site. One set included metaphases after a moderate exposure (1.3 Gy) and the other set consisted of metaphases after a high dose exposure (3.5 Gy). The laboratories used their own calibration curves for estimating doses based on observed aberration frequencies. Results: The dose estimations and 95% confidence limits were compared to the actual doses and the corresponding z-values were satisfactory for the majority; only the dose estimations from two laboratories were too low or too high. The coefficients of variation were 17.6% for the moderate and 11.2% for the high dose. Metaphases with controversial results could be identified for training purposes. Conclusions: Overall, the web based scoring of the two galleries by the 17 laboratories produced very good results. Application of web based scoring for the dicentric assay may therefore be a relevant strategy for an operational biodosimetry assistance network.

  • 26. Terzoudi, Georgia I.
    et al.
    Pantelias, Gabriel
    Darroudi, Firouz
    Barszczewska, Katarzyna
    Buraczewska, Iwona
    Depuydt, Julie
    Georgieva, Dimka
    Hadjidekova, Valeria
    Hatzi, Vasiliki I.
    Karachristou, Ioanna
    Karakosta, Maria
    Meschini, Roberta
    M'Kacher, Radhia
    Montoro, Alegria
    Palitti, Fabrizio
    Pantelias, Antonio
    Pepe, Gaetano
    Ricoul, Michelle
    Sabatier, Laure
    Sebastia, Natividad
    Sommer, Sylwester
    Vral, Anne
    Zafiropoulos, Demetre
    Wojcik, Andrzej
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute. Jan Kochanowski University, Poland.
    Dose assessment intercomparisons within the RENEB network using G(0)-lymphocyte prematurely condensed chromosomes (PCC assay)2017In: International Journal of Radiation Biology, ISSN 0955-3002, E-ISSN 1362-3095, Vol. 93, no 1, p. 48-57Article in journal (Refereed)
    Abstract [en]

    Purpose: Dose assessment intercomparisons within the RENEB network were performed for triage biodosimetry analyzing G(0)-lymphocyte PCC for harmonization, standardization and optimization of the PCC assay. Materials and methods: Comparative analysis among different partners for dose assessment included shipment of PCC-slides and captured images to construct dose-response curves for up to 6 Gy gamma-rays. Accident simulation exercises were performed to assess the suitability of the PCC assay by detecting speed of analysis and minimum number of cells required for categorization of potentially exposed individuals. Results: Calibration data based on Giemsa-stained fragments in excess of 46 PCC were obtained by different partners using galleries of PCC images for each dose-point. Mean values derived from all scores yielded a linear dose-response with approximately 4 excess-fragments/cell/Gy. To unify scoring criteria, exercises were carried out using coded PCC-slides and/or coded irradiated blood samples. Analysis of samples received 24h post-exposure was successfully performed using Giemsa staining (1 excess-fragment/cell/Gy) or centromere/telomere FISH-staining for dicentrics. Conclusions: Dose assessments by RENEB partners using appropriate calibration curves were mostly in good agreement. The PCC assay is quick and reliable for whole- or partial-body triage biodosimetry by scoring excess-fragments or dicentrics in G(0)-lymphocytes. Particularly, analysis of Giemsa-stained excess PCC-fragments is simple, inexpensive and its automation could increase throughput and scoring objectivity of the PCC assay.

  • 27. Trompier, Francois
    et al.
    Baumann, Marion
    Barrios, Lleonard
    Gregoire, Eric
    Abend, Michael
    Ainsbury, Elizabeth
    Barnard, Stephen
    Barquinero, Joan Francesc
    Antonio Bautista, Juan
    Brzozowska, Beata
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Perez-Calatayud, Jose
    De Angelis, Cinzia
    Dominguez, Inmaculada
    Hadjidekova, Valeria
    Kulka, Ulrike
    Carlos Mateos, Juan
    Meschini, Roberta
    Gil, Octavia Monteiro
    Moquet, Jayne
    Oestreicher, Ursula
    Montoro Pastor, Alegria
    Quintens, Roel
    Sebastia, Natividad
    Sommer, Sylwester
    Stoyanov, Orlin
    Thierens, Hubert
    Terzoudi, Georgia
    Ignacio Villaescusa, Juan
    Vral, Anne
    Wojcik, Andrzej
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Zafiropoulos, Demetre
    Roy, Laurence
    Investigation of the influence of calibration practices on cytogenetic laboratory performance for dose estimation2017In: International Journal of Radiation Biology, ISSN 0955-3002, E-ISSN 1362-3095, Vol. 93, no 1, p. 118-126Article in journal (Refereed)
    Abstract [en]

    Purpose: In the frame of the QA program of RENEB, an inter-laboratory comparison (ILC) of calibration sources used in biological dosimetry was achieved to investigate the influence of calibration practices and protocols on the results of the dose estimation performance as a first step to harmonization and standardization of dosimetry and irradiation practices in the European biological dosimetry network. Materials and methods: Delivered doses by irradiation facilities used by RENEB partners were determined with EPR/alanine dosimetry system. Dosimeters were irradiated in the same conditions as blood samples. A short survey was also performed to collect the information needed for the data analysis and evaluate the diversity of practices. Results: For most of partners the deviation of delivered dose from the targeted dose remains below 10%. Deviations larger than 10% were observed for five facilities out of 21. Origins of the largest discrepancies were identified. Correction actions were evaluated as satisfactory. The re-evaluation of some ILC results for the fluorescence in situ hybridization (FISH) and premature chromosome condensation (PCC) assays has been performed leading to an improvement of the overall performances. Conclusions: This work has shown the importance of dosimetry in radiobiology studies and the needs of harmonization, standardization in irradiation and dosimetry practices and educational training for biologists using ionizing radiation.

  • 28.
    Wojcik, Andrzej
    et al.
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute. Jan Kochanowski University, Poland.
    Oestreicher, Ursula
    Barrios, Lleonard
    Vral, Anne
    Terzoudi, Georgia
    Ainsbury, Elizabeth
    Rothkamm, Kai
    Trompier, Francois
    Kulka, Ulrike
    The RENEB operational basis: complement of established biodosimetric assays2017In: International Journal of Radiation Biology, ISSN 0955-3002, E-ISSN 1362-3095, Vol. 93, no 1, p. 15-19Article in journal (Refereed)
    Abstract [en]

    Purpose: To set up an operational basis of the Realizing the European Network of Biodosimetry (RENEB) network within which the application of seven established biodosimetric tools (the dicentric assay, the FISH assay, the micronucleus assay, the PCC assay, the gamma-H2AX assay, electron paramagnetic resonance and optically stimulated luminescence) will be compared and standardized among the participating laboratories. Methodology: Two intercomparisons were organized where blood samples and smartphone components were irradiated, coded and sent out to participating laboratories for dosimetric analysis. Moreover, an accident exercise was organized during which each RENEB partner had the chance to practice the procedure of activating the network and to handle large amounts of dosimetric results. Results: All activities were carried out as planned. Overall, the precision of dose estimates improved between intercomparisons 1 and 2, clearly showing the value of running such regular activities. Conclusions: The RENEB network is fully operational and ready to act in case of a major radiation emergency. Moreover, the high capacity for analyzing radiation-induced damage in cells and personal electronic devices makes the network suitable for large-scale analyses of low doses effects, where high numbers of samples must be scored in order to detect weak effects.

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