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  • 1. Ainsbury, E A
    et al.
    Bakhanova, E
    Barquinero, J F
    Brai, M
    Chumak, V
    Correcher, V
    Darroudi, F
    Fattibene, P
    Gruel, G
    Guclu, I
    Horn, S
    Jaworska, A
    Kulka, U
    Lindholm, C
    Lloyd, D
    Longo, A
    Marrale, M
    Monteiro Gil, O
    Oestreicher, U
    Pajic, J
    Rakic, B
    Romm, H
    Trompier, F
    Veronese, I
    Voisin, P
    Vral, A
    Whitehouse, C A
    Wieser, A
    Woda, C
    Wojcik, Andrzej
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för genetik, mikrobiologi och toxikologi.
    Rothkamm, K
    REVIEW OF RETROSPECTIVE DOSIMETRY TECHNIQUES FOR EXTERNAL IONISING RADIATION EXPOSURES.2011Inngår i: Radiation Protection Dosimetry, ISSN 0144-8420, E-ISSN 1742-3406, Vol. 147, nr 4, s. 573-592Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The current focus on networking and mutual assistance in the management of radiation accidents or incidents has demonstrated the importance of a joined-up approach in physical and biological dosimetry. To this end, the European Radiation Dosimetry Working Group 10 on 'Retrospective Dosimetry' has been set up by individuals from a wide range of disciplines across Europe. Here, established and emerging dosimetry methods are reviewed, which can be used immediately and retrospectively following external ionising radiation exposure. Endpoints and assays include dicentrics, translocations, premature chromosome condensation, micronuclei, somatic mutations, gene expression, electron paramagnetic resonance, thermoluminescence, optically stimulated luminescence, neutron activation, haematology, protein biomarkers and analytical dose reconstruction. Individual characteristics of these techniques, their limitations and potential for further development are reviewed, and their usefulness in specific exposure scenarios is discussed. Whilst no single technique fulfils the criteria of an ideal dosemeter, an integrated approach using multiple techniques tailored to the exposure scenario can cover most requirements.

  • 2. Ainsbury, Elizabeth A.
    et al.
    Al-hafidh, Jenna
    Bajinskis, Ainars
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
    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
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
    Inter- and intra-laboratory comparison of a multibiodosimetric approach to triage in a simulated, large scale radiation emergency2014Inngår i: International Journal of Radiation Biology, ISSN 0955-3002, E-ISSN 1362-3095, Vol. 90, nr 2, s. 193-202Artikkel i tidsskrift (Fagfellevurdert)
    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.

  • 3. Ainsbury, Elizabeth A.
    et al.
    Barnard, Stephen
    Barrios, Lleonard
    Fattibene, Paola
    de Gelder, Virginie
    Gregoire, Eric
    Lindholm, Carita
    Lloyd, David
    Nergaard, Inger
    Rothkamm, Kai
    Romm, Horst
    Scherthan, Harry
    Thierens, Hubert
    Vandevoorde, Charlot
    Woda, Clemens
    Wojcik, Andrzej
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
    MULTIBIODOSE RADIATION EMERGENCY TRIAGE CATEGORIZATION SOFTWARE2014Inngår i: Health Physics, ISSN 0017-9078, E-ISSN 1538-5159, Vol. 107, nr 1, s. 83-89Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    In this note, the authors describe the MULTIBIODOSE software, which has been created as part of the MULTIBIODOSE project. The software enables doses estimated by networks of laboratories, using up to five retrospective (biological and physical) assays, to be combined to give a single estimate of triage category for each individual potentially exposed to ionizing radiation in a large scale radiation accident or incident. The MULTIBIODOSE software has been created in Java. The usage of the software is based on the MULTIBIODOSE Guidance: the program creates a link to a single SQLite database for each incident, and the database is administered by the lead laboratory. The software has been tested with Java runtime environment 6 and 7 on a number of different Windows, Mac, and Linux systems, using data from a recent intercomparison exercise. The Java program MULTIBIODOSE_1.0.jar is freely available to download from http://www.multibiodose.eu/software or by contacting the software administrator: MULTIBIODOSE-software@gmx.com.

  • 4. 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
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
    Woda, Clemens
    Integration of new biological and physical retrospective dosimetry methods into EU emergency response plans - joint RENEB and EURADOS inter-laboratory comparisons2017Inngår i: International Journal of Radiation Biology, ISSN 0955-3002, E-ISSN 1362-3095, Vol. 93, nr 1, s. 99-109Artikkel i tidsskrift (Fagfellevurdert)
    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.

  • 5. Beltran-Pardo, Eliana A.
    et al.
    Jönsson, Ingemar
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för genetik, mikrobiologi och toxikologi. Kristianstad University, Sweden.
    Wojcik, Andrzej
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för genetik, mikrobiologi och toxikologi.
    Haghdoost, Siamak
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för genetik, mikrobiologi och toxikologi.
    Harms-Ringdahl, Mats
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för genetik, mikrobiologi och toxikologi.
    Bermudez Cruz, Rosa Maria
    Bernal Villegas, Jaime E.
    Sequence analysis of the DNA-repair gene rad51 in the tardigrades Milnesium cf. tardigradum, Hypsibius dujardini and Macrobiotus cf. harmsworthi2013Inngår i: Journal of limnology, ISSN 1129-5767, E-ISSN 1723-8633, Vol. 72, s. 80-91Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Tardigrades are known for being resistant to extreme conditions, including tolerance to ionising and UV radiation in both the hydrated and the dehydrated state. It is known that these factors may cause damage to DNA. It has recently been shown that single and double DNA strand breaks occur when tardigrades are maintained for a long time in the anhydrobiotic state. This may suggest that perhaps tardigrades rely on efficient DNA repair mechanisms. Among all proteins that comprise the DNA repair system, recombinases such as RecA or Rad51 have a very important function: DNA exchange activity. This enzyme is used in the homologous recombination and allows repair of the damaged strand using homologous non-damaged strands as a template. In this study, Rad51 induction was evaluated by western blot in Milnesium cf. tardigradum, after exposure to gamma radiation. The Rad51 protein was highly induced by radiation, when compared to the control. The rad51 genes were searched in three tardigrades: Milnesium cf. tardigradum, Hypsibius dujardini and Macrobiotus cf. harmsworthi. The gene sequences were obtained by preparing and sequencing transcriptome libraries for H. dujardini and M. cf. harmsworthi and designing rad51 degenerate primers specific for M. cf. tardigradum. Comparison of Rad51 putative proteins from tardigrades with other organisms showed that they are highly similar to the corresponding sequence from the nematode Trichinella spiralis. A structure-based sequence alignment from tardigrades and other organisms revealed that putative Rad51 predicted proteins from tardigrades contain the expected motifs for these important recombinases. In a cladogram tree based on this alignment, tardigrades tend to cluster together suggesting that they have selective differences in these genes that make them diverge between species. Predicted Rad51 structures from tardigrades were also compared with crystalline structure of Rad51 in Saccharomyces cerevisiae. These results reveal that S. cerevisiae Rad51 structure is very similar to that of the three analysed tardigrades. On the other hand the predicted structure of Rad51 from M. cf. harmsworthi and H. dujardini are closer related to each other, than each of them to that of M. cf. tardigradum.

  • 6.
    Beltran-Pardo, Eliana
    et al.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
    Jonsson, K. Ingemar
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut. Kristianstad University, Sweden.
    Harms-Ringdahl, Mats
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
    Haghdoost, Siamak
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
    Wojcik, Andrzej
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
    Tolerance to Gamma Radiation in the Tardigrade Hypsibius dujardini from Embryo to Adult Correlate Inversely with Cellular Proliferation2015Inngår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, nr 7, artikkel-id e0133658Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Tardigrades are highly tolerant to desiccation and ionizing radiation but the mechanisms of this tolerance are not well understood. In this paper, we report studies on dose responses of adults and eggs of the tardigrade Hypsibius dujardini exposed to gamma radiation. In adults the LD50/48h for survival was estimated at similar to 4200 Gy, and doses higher than 100 Gy reduced both fertility and hatchability of laid eggs drastically. We also evaluated the effect of radiation (doses 50 Gy, 200 Gy, 500 Gy) on eggs in the early and late embryonic stage of development, and observed a reduced hatchability in the early stage, while no effect was found in the late stage of development. Survival of juveniles from irradiated eggs was highly affected by a 500 Gy dose, both in the early and the late stage. Juveniles hatched from eggs irradiated at 50 Gy and 200 Gy developed into adults and produced offspring, but their fertility was reduced compared to the controls. Finally we measured the effect of low temperature during irradiation at 4000 Gy and 4500 Gy on survival in adult tardigrades, and observed a slight delay in the expressed mortality when tardigrades were irradiated on ice. Since H. dujardini is a freshwater tardigrade with lower tolerance to desiccation compared to limno-terrestrial tardigrades, the high radiation tolerance in adults, similar to limno-terrestrial tardigrades, is unexpected and seems to challenge the idea that desiccation and radiation tolerance rely on the same molecular mechanisms. We suggest that the higher radiation tolerance in adults and late stage embryos of H. dujardini (and in other studied tardigrades) compared to early stage embryos may partly be due to limited mitotic activity, since tardigrades have a low degree of somatic cell division (eutely), and dividing cells are known to be more sensitive to radiation.

  • 7.
    Beltran-Pardo, Eliana
    et al.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut. Pontificia Universidad Javeriana, Colombia.
    Jonsson, K. Ingemar
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut. Kristianstad University, Sweden.
    Wojcik, Andrzej
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
    Haghdoost, Siamak
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
    Harms-Ringdahl, Mats
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
    Bermudez-Cruz, Rosa M.
    Villegas, Jaime E. Bernal
    Effects of Ionizing Radiation on Embryos of the Tardigrade Milnesium cf. tardigradum at Different Stages of Development2013Inngår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, nr 9, artikkel-id e72098Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Tardigrades represent one of the most desiccation and radiation tolerant animals on Earth, and several studies have documented their tolerance in the adult stage. Studies on tolerance during embryological stages are rare, but differential effects of desiccation and freezing on different developmental stages have been reported, as well as dose-dependent effect of gamma irradiation on tardigrade embryos. Here, we report a study evaluating the tolerance of eggs from the eutardigrade Milnesium cf. tardigradum to three doses of gamma radiation (50, 200 and 500 Gy) at the early, middle, and late stage of development. We found that embryos of the middle and late developmental stages were tolerant to all doses, while eggs in the early developmental stage were tolerant only to a dose of 50 Gy, and showed a declining survival with higher dose. We also observed a delay in development of irradiated eggs, suggesting that periods of DNA repair might have taken place after irradiation induced damage. The delay was independent of dose for eggs irradiated in the middle and late stage, possibly indicating a fixed developmental schedule for repair after induced damage. These results show that the tolerance to radiation in tardigrade eggs changes in the course of their development. The mechanisms behind this pattern are unknown, but may relate to changes in mitotic activities over the embryogenesis and/or to activation of response mechanisms to damaged DNA in the course of development.

  • 8.
    Brehwens, Karl
    et al.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
    Bajinskis, Ainars
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut. University of Latvia, Latvia.
    Haghdoost, Siamak
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
    Wojcik, Andrzej
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut. Jan Kochanowski University, Poland.
    Micronucleus frequencies and clonogenic cell survival in TK6 cells exposed to changing dose rates under controlled temperature conditions2014Inngår i: International Journal of Radiation Biology, ISSN 0955-3002, E-ISSN 1362-3095, Vol. 90, nr 3, s. 241-247Artikkel i tidsskrift (Fagfellevurdert)
    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.

  • 9.
    Brehwens, Karl
    et al.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för genetik, mikrobiologi och toxikologi.
    Bajinskis, Ainars
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för genetik, mikrobiologi och toxikologi.
    Staaf, Elina
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för genetik, mikrobiologi och toxikologi.
    Haghdoost, Siamak
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för genetik, mikrobiologi och toxikologi.
    Cederwall, Bo
    Wojcik, Andrzej
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för genetik, mikrobiologi och toxikologi.
    A NEW DEVICE TO EXPOSE CELLS TO CHANGING DOSE RATES OF IONISING RADIATION2012Inngår i: Radiation Protection Dosimetry, ISSN 0144-8420, E-ISSN 1742-3406, Vol. 148, nr 3, s. 366-371Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    In many exposure scenarios to ionising radiation, the dose rate is not constant. Despite this, most in vitro studies aimed at investigating the effects of ionising radiation are carried out exposing samples at constant dose rates. Consequently, very little data exist on the biological effects of exposures to changing dose rates. This may be due to technical limitations of standard irradiation facilities, but also to the fact that the importance of research in this area has not been appreciated. We have recently shown that cells exposed to a decreasing dose rate suffer higher levels of cytogenetic damage than do cells exposed to an increasing or a constant dose rate. To further study the effects of changing dose rates, a new device was constructed that permits the exposure of cell samples in tubes, flasks or Petri dishes to changing dose rates of X-rays. This report presents the technical data, performance and dosimetry of this novel device.

  • 10.
    Brehwens, Karl
    et al.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för genetik, mikrobiologi och toxikologi.
    Bajinskis, Ainars
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för genetik, mikrobiologi och toxikologi.
    Staaf, Elina
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för genetik, mikrobiologi och toxikologi.
    Haghdoost, Siamak
    Wojcik, Andrzej
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för genetik, mikrobiologi och toxikologi.
    Changing dose rates influences the cellular effect of ionising radiation2011Inngår i: Strahlentherapie und Onkologie (Print), ISSN 0179-7158, E-ISSN 1439-099X, Vol. 187, s. 107-108Artikkel i tidsskrift (Fagfellevurdert)
  • 11.
    Brehwens, Karl
    et al.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för genetik, mikrobiologi och toxikologi.
    Staaf, Elina
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för genetik, mikrobiologi och toxikologi.
    Haghdoost, Siamak
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för genetik, mikrobiologi och toxikologi.
    González, Abel J
    Wojcik, Andrzej
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för genetik, mikrobiologi och toxikologi.
    Cytogenetic damage in cells exposed to ionizing radiation under conditions of a changing dose rate2010Inngår i: Radiation Research, ISSN 0033-7587, E-ISSN 1938-5404, Vol. 173, nr 3, s. 283-9Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The current international paradigm on the biological effects of radiation is based mainly on the effects of dose with some consideration for the dose rate. No allowance has been made for the potential influence of a changing dose rate (second derivative of dose), and the biological effects of exposing cells to changing dose rates have never been analyzed. This paper provides evidence that radiation effects in cells may depend on temporal changes in the dose rate. In these experiments, cells were moved toward or away from an X-ray source. The speed of movement, the time of irradiation, and the temperature during exposure were controlled. Here we report the results of the first experiments with TK6 cells that were exposed at a constant dose rate, at an increasing dose rate, or at a decreasing dose rate. The average dose rate and the total dose were same for all samples. Micronuclei were scored as the end point. The results show that the level of cytogenetic damage was higher in cells exposed to a decreasing dose rate compared to both an increasing and a constant dose rate. This finding may suggest that the second derivative of dose may influence radiation risk estimates, and the results should trigger further studies on this issue.

  • 12.
    Brzozowska, Beata
    et al.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut. 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
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut. Jan Kochanowski University, Poland.
    RENEB accident simulation exercise2017Inngår i: International Journal of Radiation Biology, ISSN 0955-3002, E-ISSN 1362-3095, Vol. 93, nr 1, s. 75-80Artikkel i tidsskrift (Fagfellevurdert)
    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.

  • 13. Brzozowska, Kinga
    et al.
    Johannes, Christian
    Obe, Gunter
    Hentschel, Reinhard
    Morand, Josselin
    Moss, Ray
    Wittig, Andrea
    Sauerwein, Wolfgang
    Liniecki, Julian
    Szumiel, Irena
    Wojcik, Andrzej
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för genetik, mikrobiologi och toxikologi.
    Effect of temperature during irradiation on the level of micronuclei in human peripheral blood lymphocytes exposed to X-rays and neutrons.2009Inngår i: International Journal of Radiation Biology, ISSN 0955-3002, E-ISSN 1362-3095, s. 1-9Artikkel i tidsskrift (Fagfellevurdert)
    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.

  • 14. Brzozowska, Kinga
    et al.
    Pinkawa, Michael
    Eble, Michael J.
    Muller, Wolfgang-Ullrich
    Wojcik, Andrzej
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för genetik, mikrobiologi och toxikologi.
    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 radiotherapy2012Inngår i: International Journal of Radiation Biology, ISSN 0955-3002, E-ISSN 1362-3095, Vol. 88, nr 5, s. 405-413Artikkel i tidsskrift (Fagfellevurdert)
    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.

  • 15.
    Cheng, Lei
    et al.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
    Brzozowska, Beata
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut. University of Warsaw, Poland.
    Sollazzo, Alice
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
    Lundholm, Lovisa
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
    Lisowska, Halina
    Haghdoost, Siamak
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
    Wojcik, Andrzej
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut. Jan Kochanowski University, Poland.
    Comet assay reveals an interaction of DNA lesions and impairment of DNA repair in peripheral blood lymphocytes simultaneously exposed to alpha particles and X-raysManuskript (preprint) (Annet vitenskapelig)
    Abstract [en]

    The biological effectiveness of ionising radiation is related to the ionisation density which is defined by the linear energy transfer LET. Radiation quality factors are applied to calculate the equivalent dose in the field of radiation protection and the biologically effective dose in the field of radiotherapy. Additivity is assumed in exposure scenarios where radiations of different qualities are mixed. We have carried out a series of studies on the cytogenetic effect of exposing human peripheral blood lymphocytes to a mixed beam of the high LET alpha radiation and low LET X-rays and could demonstrate that both radiations interact in producing more chromosomal aberrations than expected based on additivity. The aim of the present investigation was to look at the mechanism of the interaction, especially with respect to the question if it is due to an augmented level of initial damage or impaired DNA repair. The level of DNA damage and the kinetics of damage repair was quantified by the alkaline comet assay. The levels of phosphorylated, key DNA damage response (DDR) proteins were also measured by Western blotting. The results revealed that alpha particles and X-rays interact in inducing DNA damage above the level predicted by assuming additivity and that the repair of damage occurs with a delay. Moreover, the activation levels of the key DDR proteins ATM, p53 and DNA PK were highest in cells exposed to mixed beams substantiating the idea exposure to mixed beams presents a challenge to the cellular DNA damage response system. 

  • 16.
    Cheng, Lei
    et al.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
    Brzozowska, Beata
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut. University of Warsaw, Poland.
    Sollazzo, Alice
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
    Lundholm, Lovisa
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
    Lisowska, Halina
    Haghdoost, Siamak
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
    Wojcik, Andrzej
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut. Jan Kochanowski University, Poland.
    Simultaneous induction of dispersed and clustered DNA lesions compromises DNA damage response in human peripheral blood lymphocytes2018Inngår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 13, nr 10, artikkel-id e0204068Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Due to its ability to induce DNA damage in a space and time controlled manner, ionising radiation is a unique tool for studying the mechanisms of DNA repair. The biological effectiveness of ionising radiation is related to the ionisation density which is defined by the linear energy transfer (LET). Alpha particles are characterised by high LET, while X-rays by low LET values. An interesting question is how cells react when exposed to a mixed beam of high and low LET radiation. In an earlier study carried out with human peripheral blood lymphocytes (PBL) we could demonstrate that alpha radiation X-rays interact in producing more chromosomal aberrations than expected based on additivity. The aim of the present investigation was to look at the mechanism of the interaction, especially with respect to the question if it is due to an augmented level of initial damage or impaired DNA repair. PBL were exposed to various doses of alpha particles, X-rays and mixed beams. DNA damage and the kinetics of damage repair was quantified by the alkaline comet assay. The levels of phosphorylated, key DNA damage response (DDR) proteins ATM, p53 and DNA-PK were measured by Western blotting and mRNA levels of 6 damage-responsive genes were measured by qPCR. Alpha particles and X-rays interact in inducing DNA damage above the level predicted by assuming additivity and that the repair of damage occurs with a delay. The activation levels of DDR proteins and mRNA levels of the studied genes were highest in cells exposed to mixed beams. The results substantiate the idea that exposure to mixed beams presents a challenge for the cellular DDR system.

  • 17.
    Cheng, Lei
    et al.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
    Lisowska, Halina
    Sollazzo, Alice
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
    Wegierek-Ciuk, Aneta
    Stepien, Katarzyna
    Kuszewski, Tomasz
    Lankoff, Anna
    Haghdoost, Siamak
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
    Wojcik, Andrzej
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
    Modulation of radiation-induced cytogenetic damage in human peripheral blood lymphocytes by hypothermia2015Inngår i: Mutation research. Genetic toxicology and environmental mutagenesis, ISSN 1383-5718, E-ISSN 1879-3592, Vol. 793, nr SI, s. 96-100Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Purpose: Recent studies have shown that low temperature (hypothermia) at exposure can act in a radioprotective manner at the level of cytogenetic damage. The mechanisms of this phenomenon are not understood, but it was suggested to be due to hypothermia-induced perturbations of the cell cycle. The purpose of the present study was to detect whether a reduced frequency of micronuclei is observed in peripheral blood lymphocytes (PBL) irradiated at low temperature and harvested sequentially at 3 time points. Additionally, the level of apoptosis was estimated by microscopic analysis of the MN slides. Materials and methods: Experiments were carried out with blood drawn from three donors at the Stockholm University and from three donors at the Jan Kochanowski University. Prior to irradiation, blood samples were incubated for 20 mm and irradiated at the respective temperature (0 degrees C and 37 degrees C) with gamma rays. Whole blood cultures were set up, cytochalasin B was added after 44h of irradiation and the samples were harvested after 72,96 and 120 h of incubation time. Results and conclusions: The frequency of micronuclei was markedly lower in PBL harvested at 72h, 96 h and 120 h following irradiation at 0 degrees C as compared to 37 degrees C. This indicates that the temperature effect observed in peripheral blood lymphocytes after irradiation is not related to a temporary perturbation of the cell cycle. Also, it is not due to selective elimination of damaged cells by apoptosis.

  • 18. Chiba, Mitsuru
    et al.
    Monzen, Satoru
    Iwaya, Chihiro
    Kashiwagi, Yuri
    Yamada, Sunao
    Hosokawa, Yoichiro
    Mariya, Yasushi
    Nakamura, Toshiya
    Wojcik, Andrzej
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut. Jan Kochanowski University, Poland.
    Serum miR-375-3p increase in mice exposed to a high dose of ionizing radiation2018Inngår i: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, artikkel-id 1302Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Exposure to high-doses of ionizing radiation (IR) leads to development of a strong acute radiation syndrome (ARS) in mammals. ARS manifests after a latency period and it is important to develop fast prognostic biomarkers for its early detection and assessment. Analysis of chromosomal aberrations in peripheral blood lymphocytes is the gold standard of biological dosimetry, but it fails after high doses of IR. Therefore, it is important to establish novel biomarkers of exposure that are fast and reliable also in the high dose range. Here, we investigated the applicability of miRNA levels in mouse serum. We found significantly increased levels of miR-375-3p following whole body exposure to 7 Gy of X-rays. In addition, we analyzed their levels in various organs of control mice and found them to be especially abundant in the pancreas and the intestine. Following a dose of 7 Gy, extensive cell death occurred in these tissues and this correlated negatively with the levels of miR-375-3p in the organs. We conclude that high expressing tissues of miR-375-3p may secrete this miRNA in serum following exposure to 7 Gy. Therefore, elevated miR-375-3p in serum may be a predictor of tissue damage induced by exposure to a high radiation dose.

  • 19. Cho, Kunwoo
    et al.
    Imaoka, Tatsuhiko
    Klokov, Dmitry
    Paunesku, Tatjana
    Salomaa, Sisko
    Birschwilks, Mandy
    Bouffler, Simon
    Brooks, Antone L.
    Hei, Tom K.
    Iwasaki, Toshiyasu
    Ono, Tetsuya
    Sakai, Kazuo
    Wojcik, Andrzej
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
    Woloschak, Gayle E.
    Yamada, Yutaka
    Hamada, Nobuyuki
    Funding for radiation research: past, present and future2019Inngår i: International Journal of Radiation Biology, ISSN 0955-3002, E-ISSN 1362-3095, Vol. 95, nr 7, s. 816-840Artikkel, forskningsoversikt (Fagfellevurdert)
    Abstract [en]

    For more than a century, ionizing radiation has been indispensable mainly in medicine and industry. Radiation research is a multidisciplinary field that investigates radiation effects. Radiation research was very active in the mid- to late 20th century, but has then faced challenges, during which time funding has fluctuated widely. Here we review historical changes in funding situations in the field of radiation research, particularly in Canada, European Union countries, Japan, South Korea, and the US. We also provide a brief overview of the current situations in education and training in this field. A better understanding of the biological consequences of radiation exposure is becoming more important with increasing public concerns on radiation risks and other radiation literacy. Continued funding for radiation research is needed, and education and training in this field are also important.

  • 20. Czub, Joanna
    et al.
    Banaś, Dariusz
    Braziewicz, Janusz
    Buraczewska, Iwona
    Jaskóła, Marian
    Kaźmierczak, Urszula
    Korman, Andrzej
    Lankoff, Anna
    Lisowska, Halina
    Szefliński, Zygmunt
    Wojewódzka, Maria
    Wójcik, Andrzej
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut. Jan Kochanowski University, Poland.
    Biological effects of mixed-ion beams. Part 1: Effect of irradiation of the CHO-K1 cells with a mixed-ion beam containing the carbon and oxygen ions2018Inngår i: Applied Radiation and Isotopes, ISSN 0969-8043, E-ISSN 1872-9800, Vol. 139, s. 304-309Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Carbon and oxygen ions were accelerated simultaneously to estimate the effect of irradiation of living cells with the two different ions. This mixed ion beam was used to irradiate the CHO-K1 cells, and a survival test was performed. The type of the effect of the mixed ion beam on the cells was determined with the isobologram method, whereby survival curves for irradiations with individual ion beams were also used. An additive effect of irradiation with the two ions was found.

  • 21. Czub, Joanna
    et al.
    Banaś, Dariusz
    Braziewicz, Janusz
    Buraczewska, Iwona
    Jaskóła, Marian
    Kaźmierczak, Urszula
    Korman, Andrzej
    Lankoff, Anna
    Lisowska, Halina
    Szefliński, Zygmunt
    Wojewódzka, Maria
    Wójcik, Andrzej
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut. Jan Kochanowski University, Poland.
    Biological effects of mixed-ion beams. Part 2: The relative biological effectiveness of CHO-K1 cells irradiated by mixed- and single-ion beams2019Inngår i: Applied Radiation and Isotopes, ISSN 0969-8043, E-ISSN 1872-9800, Vol. 150, s. 192-198Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The relative biological effectiveness (RBE) values were determined for single- and mixed-ion beams containing carbon and oxygen ions. The CHO-K1 cells were irradiated with beams with the linear energy transfer (LET) values of 236-300 and 461-470 keV/mu m for C-12 and O-16 ions, respectively. The RBE was estimated as a function of dose, survival fraction (SF) and LET. The SF was not affected by varying contributions of the constituent ions to the total mixed dose. The RBE has the same value for single-ion exposures with ions with LET 300 (C-12) and 470 keV/mu m (O-16).

  • 22.
    Dang, Li
    et al.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för genetik, mikrobiologi och toxikologi.
    Lisowska, Halina
    Shakeri Manesh, Sara
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för genetik, mikrobiologi och toxikologi.
    Sollazzo, Alice
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för genetik, mikrobiologi och toxikologi.
    Deperas-Kaminska, Marta
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för genetik, mikrobiologi och toxikologi. Jan Kochanowski University, Poland.
    Staaf, Elina
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för genetik, mikrobiologi och toxikologi.
    Haghdoost, Siamak
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för genetik, mikrobiologi och toxikologi.
    Brehwens, Karl
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för genetik, mikrobiologi och toxikologi.
    Wojcik, Andrzej
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för genetik, mikrobiologi och toxikologi. Jan Kochanowski University, Poland.
    Radioprotective effect of hypothermia on cells - a multiparametric approach to delineate the mechanisms2012Inngår i: International Journal of Radiation Biology, ISSN 0955-3002, E-ISSN 1362-3095, Vol. 88, nr 7, s. 507-514Artikkel i tidsskrift (Fagfellevurdert)
    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.

  • 23. Danielsson, Daniel
    et al.
    Brehwens, Karl
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
    Halle, Martin
    Marczyk, Michal
    Sollazzo, Alice
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
    Polanska, Joanna
    Munck-Wikland, Eva
    Wojcik, Andrzej
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut. Jan Kochanowski University, Poland.
    Haghdoost, Siamak
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
    Influence of genetic background and oxidative stress response on risk of mandibular osteoradionecrosis after radiotherapy of head and neck cancer2016Inngår i: Head and Neck, ISSN 1043-3074, E-ISSN 1097-0347, Vol. 38, nr 3, s. 387-393Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Osteoradionecrosis (ORN) of the mandible is a severe complication of head and neck radiotherapy (RT) treatment, where the impact of individual radiosensitivity has been a suggested explanation. Methods: A cohort of patients with stage II/III ORN was compared to matched controls. Blood was collected and irradiated in vitro to study the capacity to handle radiation-induced oxidative stress. Patients were also genotyped for 8 single-nucleotide polymorphisms (SNPs) in genes involved in the oxidative stress response. Results: A difference in 8-oxo-7,8-dihydro-2-deoxyguanosine (8-oxo-dG) levels was found between the patient cohorts (p = 0.01). The SNP rs1695 in glutathione s-transferase p1 (GSTP1) was also found to be more frequent in the patients with ORN (p = .02). Multivariate analysis of the clinical and biological factors revealed concomitant brachytherapy plus the 2 biomarkers to be significant factors which influense risk of mandibular osteoradionecrosis after radiotherapy of head and neck cancer. Conclusion: The current study indicates that oxidative stress response contributes to individual radiosensitivity and healthy tissue damage caused by RT and may be predicted by biomarker analysis.

  • 24.
    Deperas-Kaminska, Marta
    et al.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut. Institute of Mother and Child, Poland.
    Bajinskis, Ainars
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut. University of Latvia, Latvia.
    Marczyk, Michal
    Polanska, Joanna
    Wersäll, Peter
    Lidbrink, Elisabet
    Ainsbury, Elizabeth A.
    Guipaud, Oliver
    Benderitter, Marc
    Haghdoost, Siamak
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
    Wojcik, Andrzej
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut. Jan Kochanowski University, Poland.
    RADIATION-INDUCED CHANGES IN LEVELS OF SELECTED PROTEINS IN PERIPHERAL BLOOD SERUM OF BREAST CANCER PATIENTS AS A POTENTIAL TRIAGE BIODOSIMETER FOR LARGE-SCALE RADIOLOGICAL EMERGENCIES2014Inngår i: Health Physics, ISSN 0017-9078, E-ISSN 1538-5159, Vol. 107, nr 6, s. 555-563Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The threat of a large scale radiological emergency, where thousands of people may require fast biological dosimetry for the purpose of triage, makes it necessary to search for new, high throughput biological dosimeters. The authors tested an assay based on the quantitative analysis of selected proteins in peripheral blood serum. They were particularly interested in testing proteins that are specific to irradiation of skin, as these can be used in cases of partial body exposure. Candidate proteins were identified in an earlier study with mice, where skin of the animals was exposed to different doses of radiation and global expression of serum proteins was analyzed. Eight proteins were found, the expression of which showed a consistent dose-response relationship. Human analogues of these proteins were identified, and their expression was measured in peripheral blood serum of 16 breast cancer patients undergoing external beam radiotherapy. The proteins were Apolipoprotein E; Apolipoprotein H; Complement protein 7; Prothrombinase; Pantothenate Kinase 4; Alpha-2-macroglobulin; Fetuin B and Alpha-1-Anti-Chymotrypsin. Measurements were carried out in blood samples collected prior to exposure (control), on the day after one fraction (2 Gy), on the day after five fractions (10 Gy), on the day after 10 fractions (20 Gy), and 1 mo after 23-25 fractions (total dose of 46-50 Gy). Multivariate analysis was carried out, and a multinomial logistic regression model was built. The results indicate that the combined analysis of Apolipoprotein E, Factor X, and Pantothenate Kinase 4 allows discriminating between exposure to 2 Gy and lower and between 10 Gy and higher. The discrimination is possible up to 1 mo after exposure.

  • 25. Deperas-Kaminska, Marta
    et al.
    Zaytseva, Ekaterina M.
    Deperas-Standylo, Joanna
    Mitsyn, Gennady V.
    Molokanov, Alexander G.
    Timoshenko, Gennady N.
    Wojcik, Andrzej
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för genetik, mikrobiologi och toxikologi.
    Inter-chromosomal variation in aberration frequencies in human lymphocytes exposed to charged particles of LET between 0.5 and 55 keV/mu m2010Inngår i: International Journal of Radiation Biology, ISSN 0955-3002, E-ISSN 1362-3095, Vol. 86, nr 11, s. 975-985Artikkel i tidsskrift (Fagfellevurdert)
    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.

  • 26. 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
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
    Vral, Anne
    RENEB intercomparison exercises analyzing micronuclei (Cytokinesis-block Micronucleus Assay)2017Inngår i: International Journal of Radiation Biology, ISSN 0955-3002, E-ISSN 1362-3095, Vol. 93, nr 1, s. 36-47Artikkel i tidsskrift (Fagfellevurdert)
    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.

  • 27.
    Elvers, Ingegerd
    et al.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för genetik, mikrobiologi och toxikologi.
    Deperas-Kaminska, Marta
    Joint Institute for Nuclear Research, Dubna, Russia.
    Johansson, Fredrik
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för genetik, mikrobiologi och toxikologi.
    Schultz, Niklas
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för genetik, mikrobiologi och toxikologi.
    Wojcik, Andrzej
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för genetik, mikrobiologi och toxikologi.
    Helleday, Thomas
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för genetik, mikrobiologi och toxikologi.
    UV-induced replication fork collapse in DNA polymerase η deficient cells is independent of the MUS81 endonucleaseManuskript (preprint) (Annet vitenskapelig)
    Abstract [en]

    The MUS81 endonuclease was initially identified in resonse to UV and MMS lesions, and has been implicated in replication fork collapse after exposure to cross-linking agents. After stalling of replication forks by hydroxyurea treatment, the forks collapse independently of MUS81 but the endonuclease is required for replication fork restart. However in cells deficient in the Werner helicase, MUS81 is needed for collapse of replication forks after hydroxyurea treatment, indicating that the endonuclease might play a role in replication fork collapse in cells with impaired replication. UV irradiation induces DNA damage that physically block replication fork elongation but may be bypassed by translesion synthesis polymerases. Here we have investigated the role of MUS81 after UV irradiation of human fibroblasts deficient in Polη, and restored (wild-type) cells. We show that in wild-type cells, depletion of MUS81 does not affect survival after UV irradiation. However in Polη deficient cells, MUS81 depletion further lowers the survival after exposure to UV. In spite of this, replication forks collapse in UV irradiated Polη deficient cells independently of MUS81.

  • 28. Fattibene, Paola
    et al.
    Wojcik, Andrzej
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för genetik, mikrobiologi och toxikologi.
    Biodosimetric tools for a fast triage of people accidentally exposed to ionising radiation.2009Inngår i: Annali dell'Istituto superiore di sanità, ISSN 0021-2571, Vol. 45, nr 3, s. 245-Artikkel i tidsskrift (Fagfellevurdert)
  • 29.
    Fotouhi, Asal
    et al.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
    Cornella, Nicola
    Ramezani, Mehrafarin
    Wojcik, Andrzej
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
    Haghdoost, Siamak
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
    Investigation of micronucleus induction in MTH1 knockdown cells exposed to UVA, UVB, and UVCManuskript (preprint) (Annet vitenskapelig)
  • 30.
    Fotouhi, Asal
    et al.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
    Cornella, Nicola
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
    Ramezani, Mehrafarin
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
    Wojcik, Andrzej
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
    Haghdoost, Siamak
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
    Investigation of micronucleus induction in MTH1 knockdown cells exposed to UVA, UVB or UVC2015Inngår i: Mutation research. Genetic toxicology and environmental mutagenesis, ISSN 1383-5718, E-ISSN 1879-3592, Vol. 793, nr SI, s. 161-165Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The longer wave parts of UVR can increase the production of reactive oxygen species (ROS) which can oxidize nucleotides in the DNA or in the nucleotide pool leading to mutations. Oxidized bases in the DNA are repaired mainly by the DNA base excision repair system and incorporation of oxidized nucleotides into newly synthesized DNA can be prevented by the enzyme MTH1. Here we hypothesize that the formation of several oxidized base damages (from pool and DNA) in close proximity, would cause a high number of base excision repair events, leading to DNA double strand breaks (DSB) and therefore giving rise to cytogenetic damage. If this hypothesis is true, cells with low levels of MTH1 will show higher cytogenetic damage after the longer wave parts of UVR. We analyzed micronuclei induction (MN) as an endpoint for cytogenetic damage in the human lymphoblastoid cell line, TK6, with a normal and a reduced level of MTH1 exposed to UVR. The results indicate a higher level of micronuclei at all incubation times after exposure to the longer wave parts of UVR. There is no significant difference between wildtype and MTH1-knockdown TK6 cells, indicating that MTH1 has no protective role in UVR-induced cytogenetic damage. This indicates that DSBs induced by UV arise from damage forms by direct interaction of UV or ROS with the DNA rather than through oxidation of dNTP.

  • 31.
    Fotouhi, Asal
    et al.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
    Hagos, Winta Woldai
    Ilic, Marina
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
    Wojcik, Andrzej
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
    Harms-Ringdahl, Mats
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
    De Gruij, Frank
    Mullenders, Leon
    Jansen, Jacob G.
    Haghdoost, Siamak
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
    Analysis of mutant frequencies and mutation spectra in hMTH1 knockdown TK6 cells exposed to UV radiation2013Inngår i: Mutation research, ISSN 0027-5107, E-ISSN 1873-135X, Vol. 751, s. 8-14Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Ultraviolet radiation is a highly mutagenic agent that damages the DNA by the formation of mutagenic photoproducts at dipyrimidine sites and by oxidative DNA damages via reactive oxygen species (ROS). ROS can also give rise to mutations via oxidation of dNTPs in the nucleotide pool, e.g. 8-oxo-dGTP and 2-OH-dATP and subsequent incorporation during DNA replication. Here we show that expression of human MutT homolog 1 (hMTH1) which sanitizes the nucleotide pool by dephosphorylating oxidized dNTPs, protects against mutagenesis induced by long wave UVA light and by UVB light but not by short wave UVC light. Mutational spectra analyses of UVA-induced mutations at the endogenous Thymidine kinase gene in human lymphoblastoid cells revealed that hMTH1 mainly protects cells from transitions at GC and AT base pairs.

  • 32.
    Fotouhi, Asal
    et al.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för genetik, mikrobiologi och toxikologi.
    Skiöld, Sara
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för genetik, mikrobiologi och toxikologi.
    Shakeri Manesh, Sara
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för genetik, mikrobiologi och toxikologi.
    Osterman-Golkar, Siv
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för genetik, mikrobiologi och toxikologi.
    Wojcik, Andrzej
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för genetik, mikrobiologi och toxikologi.
    Jenssen, Dag
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för genetik, mikrobiologi och toxikologi.
    Harms-Ringdahl, Mats
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för genetik, mikrobiologi och toxikologi.
    Haghdoost, Siamak
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för genetik, mikrobiologi och toxikologi.
    Reduction of 8-oxodGTP in the nucleotide pool by hMTH1 leads to reduction in mutations in the human lymphoblastoid cell line TK6 exposed to UVA2011Inngår i: Mutation research, ISSN 0027-5107, E-ISSN 1873-135X, Vol. 715, nr 1-2, s. 13-18Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    UVA has been suggested to play an important role in UV-induced mutagenesis. The mechanisms by which UVA induces mutations are still a matter of debate. Our aim was to investigate the protective capacity of hMTH1, a nucleotide pool sanitization enzyme with 8-oxodGTPase activity. Human B lymphoblastoid cells were stably transfected with shRNA directed against hMTH1. Clonogenic survival, mutations, intracellular and extracellular levels of 8-oxodG (8-oxo-7, 8-dihydro-2'-deoxyguanosine) and dG in the nucleotide pool of UVA-irradiated transfected and non-transfected cells were investigated. Mutations were determined in the thymidine kinase locus. Intracellular 8-oxodG and dG were measured using a modified ELISA and HPLC, respectively, after extraction of the nucleotide pool and conversion of nucleotides to their corresponding nucleosides. 8-oxodG in the medium was measured using ELISA. UVA-induced mutations were significantly higher while the survival was slightly lower in transfected compared to non-transfected cells. The increased mutation rate in transfected cells at increased exposure correlated with enhanced levels of 8-oxodG in the nucleotide pool, and a somewhat reduced level of 8-oxodG in the medium. The results indicate that the nucleotide pool is a significant target for UVA-induced mutations and implicates that hMTH1 plays an important role in protecting cells from UVA-induced oxidative stress.

  • 33. 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
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
    Barrios, Leonardo
    RENEB biodosimetry intercomparison analyzing translocations by FISH2017Inngår i: International Journal of Radiation Biology, ISSN 0955-3002, E-ISSN 1362-3095, Vol. 93, nr 1, s. 30-35Artikkel i tidsskrift (Fagfellevurdert)
    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.

  • 34. Gałecki, Maciej
    et al.
    Tartas, Adrianna
    Szymanek, Agata
    Sims, Emma
    Lundholm, Lovisa
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
    Sollazzo, Alice
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
    Cheng, Lei
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
    Fujishima, Yohei
    Yoshida, Mitsuaki A.
    Żygierewicz, Jarosław
    Wojcik, Andrzej
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut. Jan Kochanowski University, Poland.
    Brzozowska-Wardecka, Beata
    Precision of scoring radiation-induced chromosomal aberrations and micronuclei by unexperienced scorers2019Inngår i: International Journal of Radiation Biology, ISSN 0955-3002, E-ISSN 1362-3095, Vol. 95, nr 9, s. 1251-1258Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Purpose: Dose assessment plays an important role in case of radiological accidents and can be performed by scoring structural changes of chromosome morphology induced in cells by ionizing radiation. The results of such a test are biased by scorer experience, therefore, simple to learn assays are recommended to be used when fast analysis of a large amount of data is needed. The aim of this study was to compare the performance of two radiobiological assays - chromosomal aberrations and micronuclei - by unexperienced scorers with the reference values generated by an expert.

    Materials and methods: Each participant of an EU-funded two-week radiobiology course was asked to score Chinese hamster ovary cells exposed to gamma radiation up to 4 Gy. The congruence of students' and expert's scores at each dose and the coherence of the dose-response curve parameters between the students were investigated.

    Results: Micronucleus test tended to be faster and easier to learn than scoring chromosomal aberrations. However, both assays carried out by inexperienced students showed reasonable dose-response curves.

    Conclusions: In the case of a large radiological accident involving many casualties, the unexperienced scorers would support the process of biodosimetric triage by cytogenetic biological dosimetry.

  • 35. Hendry, Jolyon H
    et al.
    Simon, Steven L
    Wojcik, Andrzej
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för genetik, mikrobiologi och toxikologi.
    Sohrabi, Mehdi
    Burkart, Werner
    Cardis, Elisabeth
    Laurier, Dominique
    Tirmarche, Margot
    Hayata, Isamu
    Human exposure to high natural background radiation: what can it teach us about radiation risks?2009Inngår i: Journal of Radiological Protection, ISSN 0952-4746, E-ISSN 1361-6498, Vol. 29, nr 2A, s. A29-42Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Natural radiation is the major source of human exposure to ionising radiation, and its largest contributing component to effective dose arises from inhalation of (222)Rn and its radioactive progeny. However, despite extensive knowledge of radiation risks gained through epidemiologic investigations and mechanistic considerations, the health effects of chronic low-level radiation exposure are still poorly understood. The present paper reviews the possible contribution of studies of populations living in high natural background radiation (HNBR) areas (Guarapari, Brazil; Kerala, India; Ramsar, Iran; Yangjiang, China), including radon-prone areas, to low dose risk estimation. Much of the direct information about risk related to HNBR comes from case-control studies of radon and lung cancer, which provide convincing evidence of an association between long-term protracted radiation exposures in the general population and disease incidence. The success of these studies is mainly due to the careful organ dose reconstruction (with relatively high doses to the lung), and to the fact that large-scale collaborative studies have been conducted to maximise the statistical power and to ensure the systematic collection of information on potential confounding factors. In contrast, studies in other (non-radon) HNBR areas have provided little information, relying mainly on ecological designs and very rough effective dose categorisations. Recent steps taken in China and India to establish cohorts for follow-up and to conduct nested case-control studies may provide useful information about risks in the future, provided that careful organ dose reconstruction is possible and information is collected on potential confounding factors.

  • 36. Jaworska, Alicja
    et al.
    Ainsbury, Elizabeth A.
    Fattibene, Paola
    Lindholm, Carita
    Oestreicher, Ursula
    Rothkamm, Kai
    Romm, Horst
    Thierens, Hubert
    Trompier, Francois
    Voisin, Philippe
    Vral, Anne
    Woda, Clemens
    Wojcik, Andrzej
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
    Operational guidance for radiation emergency response organisations in Europe for using biodosimetric tools developed in EU MULTIBIODOSE project2015Inngår i: Radiation Protection Dosimetry, ISSN 0144-8420, E-ISSN 1742-3406, Vol. 164, nr 1-2, s. 165-169Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    In the event of a large-scale radiological emergency, the triage of individuals according to their degree of exposure forms an important initial step of the accident management. Although clinical signs and symptoms of a serious exposure may be used for radiological triage, they are not necessarily radiation specific and can lead to a false diagnosis. Biodosimetry is a method based on the analysis of radiation-induced changes in cells of the human body or in portable electronic devices and enables the unequivocal identification of exposed people who should receive medical treatment. The MULTIBIODOSE (MBD) consortium developed and validated several biodosimetric assays and adapted and tested them as tools for biological dose assessment in a mass-casualty event. Different biodosimetric assays were validated against the 'gold standard' of biological dosimetry-the dicentric assay. The assays were harmonised in such a way that, in an emergency situation, they can be run in parallel in a network of European laboratories. The aim of this guidance is to give a concise overview of the developed biodosimetric tools as well as how and when they can be used in an emergency situation.

  • 37. Johannes, Christian
    et al.
    Dixius, Anne
    Pust, Mareike
    Hentschel, Reinhard
    Buraczewska, Iwona
    Staaf, Elina
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för genetik, mikrobiologi och toxikologi.
    Brehwens, Karl
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för genetik, mikrobiologi och toxikologi.
    Haghdoost, Siamak
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för genetik, mikrobiologi och toxikologi.
    Nievaart, Sander
    Czub, Joanna
    Braziewicz, Janusz
    Wojcik, Andrzej
    The yield of radiation-induced micronuclei in early and late-arising binucleated cells depends on radiation quality.2010Inngår i: Mutation research, ISSN 0027-5107, E-ISSN 1873-135X, Vol. 701, nr 1, s. 80-5Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    There are conflicting data regarding the effect of culturing time of human peripheral blood lymphocytes on the yield of chromosomal aberrations induced by sparsely ionising radiation in the G0 phase of the cell cycle. While some authors find that the yield of aberrations does not change with time, others find increased frequencies of aberrations with harvesting time. The reasons for the conflicting results are not known, but the majority of studies were performed with lymphocytes of a single donor collected at one time point. We performed a study to verify if individual variability could be a confounding factor. As a positive control, lymphocytes were also exposed to high LET radiation (neutrons and alpha-rays), where an effect of harvesting time on the level of damage is expected to be seen. Blood was drawn from a total of 8 donors at two time points and exposed to X-rays, 6 MeV neutrons or alpha particles generated by an Am-241 source. Whole blood cultures were set up and micronuclei (Mn) were scored in binucleated cells harvested after 72, 96 and 120 h of culture time. The results show that in lymphocytes exposed to X-rays, the frequency of Mn was generally not influenced by the culture time while for both neutrons and alpha particles consistently increased micronucleus frequencies with culture time were detected. Some individual variability was detected and the conflicting results regarding the relationship between the yield of cytogenetic damage and lymphocyte culture time can, at least partly, be due to this variability.

  • 38. Jonsson, K. Ingemar
    et al.
    Wojcik, Andrzej
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
    Tolerance to X-rays and Heavy Ions (Fe, He) in the Tardigrade Richtersius coronifer and the Bdelloid Rotifer Mniobia russeola2017Inngår i: Astrobiology, ISSN 1531-1074, E-ISSN 1557-8070, Vol. 17, nr 2, s. 163-167Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The aim of this study was to analyze tolerance to heavy ions in desiccated animals of the eutardigrade Richtersius coronifer and the bdelloid rotifer Mniobia russeola within the STARLIFE project. Both species were exposed to iron (Fe) and helium (He) ions at the Heavy Ion Medical Accelerator in Chiba (HIMAC) in Chiba, Japan, and to X-rays at the German Aerospace Center (DLR) in Cologne, Germany. Results show no effect of Fe and He on viability up to 7 days post-rehydration in both R. coronifer and M. russeola, while X-rays tended to reduce viability in R. coronifer at the highest doses. Mean egg production rate tended to decline with higher doses in R. coronifer for all radiation types, but the pattern was not statistically confirmed. In M. russeola, there was no such tendency for a dose response in egg production rate. These results confirm the previously reported high tolerance to high linear energy transfer (LET) radiation in tardigrades and show for the first time that bdelloid rotifers are also very tolerant to high-LET radiation. These animal phyla represent the most desiccation-and radiation-tolerant animals on Earth and provide excellent eukaryotic models for astrobiological research.

  • 39. Jucha, Anna
    et al.
    Wegierek-Ciuk, Aneta
    Koza, Zbigniew
    Lisowska, Halina
    Wojcik, Andrzej
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för genetik, mikrobiologi och toxikologi.
    Wojewodzka, Maria
    Lankoff, Anna
    FociCounter: A freely available PC programme for quantitative and qualitative analysis of gamma-H2AX foci2010Inngår i: Mutation research, ISSN 0027-5107, E-ISSN 1873-135X, Vol. 696, nr 1, s. 16-20Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Gamma-H2AX foci are sensitive and specific indicator for the induction of DNA double-strand breaks (DSBs) and an immunocytochemical assay with antibodies recognizing gamma-H2AX has become the gold standard for the detection of this type of DNA lesion. Quantification of gamma-H2AX foci can be achieved by various methods such as Western blotting, flow cytometry, visual analysis and computational analysis with a fluorescence microscope. The best sensitivity is achieved by computer analysis. Since no freeware programme for the analysis of gamma-H2AX foci exists for a PC platform, the aim of our study was to develop a simple and user-friendly public-domain software. The algorithm applied in our programme allows determination of the number of foci in a single cell, a focus intensity per cell, as well as a cell intensity. Its graphical user interface is based on a GTK+ library and the whole application can be run under a variety of operating systems, including MS Windows and Linux. The programme called FociCounter is publicly available at http://focicounter.sourceforge.net. Application of the programme was tested by analysing gamma-H2AX foci in CHO and MO59K cells irradiated in vitro with X-rays and validated by comparing the results obtained with the outcome of automated image analysis and flow cytometry.

  • 40.
    Jönsson, Ingemar
    et al.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut. Kristianstad University, Sweden.
    Beltran-Pardo, Eliana A.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut. Pontificia Universidad Javeriana, Colombia.
    Haghdoost, Siamak
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
    Wojcik, Andrzej
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
    Maria Bermudez-Cruz, Rosa
    Bernal Villegas, Jaime E.
    Harms-Ringdahl, Mats
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
    Tolerance to gamma-irradiation in eggs of the tardigrade Richtersius coronifer depends on stage of development2013Inngår i: Journal of limnology, ISSN 1129-5767, E-ISSN 1723-8633, Vol. 72, s. 73-79Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Tardigrades are known as one of the most radiation tolerant animals on Earth, and several studies on tolerance in adult tardigrades have been published. In contrast, very few studies on radiation tolerance of embryonic stages have been reported. Here we report a study on tolerance to gamma irradiation in eggs of the eutardigrade Richtersius coronifer. Irradiation of eggs collected directly from a natural substrate (moss) showed a clear dose-response, with a steep decline in hatchability at doses up to 0.4 kGy followed by a relatively constant hatchability around 25% up to 2 kGy, and a decline to ca. 5% at 4 kGy above which no eggs hatched. Analysis of the time required for eggs to hatch after irradiation (residual development time) showed that hatching of eggs after exposure to high doses of gamma radiation was associated with short residual development time. Since short residual development time means that the egg was irradiated at a late developmental stage, this suggests that eggs were more tolerant to radiation late in development. This was also confirmed in another experiment in which stage of development at irradiation was controlled. No eggs irradiated at the early developmental stage hatched, and only one egg at middle stage hatched, while eggs irradiated in the late stage hatched at a rate indistinguishable from controls. This suggests that the eggs are more sensitive to radiation in the early stages of development, or that tolerance to radiation is acquired only late in development, shortly before the eggs hatch, hypotheses that are not mutually exclusive. Our study emphasizes the importance of considering specific cell cycle phases and developmental stages in studies of tolerance to radiation in tardigrades, and the potential importance of embryonic studies in revealing the mechanisms behind the radiation tolerance of tardigrades and other cryptobiotic animals.

  • 41. Kacprzak, Justyna
    et al.
    Kuszewski, Tomasz
    Lankoff, Anna
    Mueller, Wolfgang-Ulrich
    Wojcik, Andrzej
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
    Lisowska, Halina
    Individual variations in the micronucleus assay for biological dosimetry after high dose exposure2013Inngår i: Mutation research. Genetic toxicology and environmental mutagenesis, ISSN 1383-5718, E-ISSN 1879-3592, Vol. 756, nr 1-2, s. 196-200Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The micronucleus assay is widely used as a biological dosimeter. Due to an inhibitory effect of radiation on cell proliferation the assay yields satisfactory results only when the absorbed dose is below about 5 Gy. In 2002 Muller and Rode suggested that a modified version of the test, based on the analysis of the ratio of trinucleated to tetranucleated cells and the frequency of micronuclei (Mn) in binucleated cells containing at least one Mn, can be applied to detect a dose reaching 15 Gy (Mutat. Res. 502 (2002) 47-51). Their conclusion was based on the results of experiments with lymphocytes from one donor and nothing is known about the possible influence of individual variability on the applicability of the Mn test to detect high doses of radiation. The aim of the present study was to validate the modified micronucleus assay with lymphocytes of 5 donors. Their blood was exposed to 0, 5, 10, 15 and 20 Gy of Co-60 gamma rays. The levels of Mn and of cell proliferation were assessed using various approaches. A strong inter-individual variability was observed for all endpoints. The results clearly show that the assessment of cell proliferation is essential for the interpretation of results. Unfortunately, it was not possible to identify one single proliferation marker that gives all necessary information.

  • 42. Kulka, U.
    et al.
    Ainsbury, L.
    Atkinson, M.
    Barnard, S.
    Smith, R.
    Barquinero, J. F.
    Barrios, L.
    Bassinet, C.
    Beinke, C.
    Cucu, A.
    Darroudi, F.
    Fattibene, P.
    Bortolin, E.
    Della Monaca, S.
    Gil, O.
    Gregoire, E.
    Hadjidekova, V.
    Haghdoost, Siamak
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
    Hatzi, V.
    Hempel, W.
    Herranz, R.
    Jaworska, A.
    Lindholm, C.
    Lumniczky, K.
    M'kacher, R.
    Moertl, S.
    Montoro, A.
    Moquet, J.
    Moreno, M.
    Noditi, M.
    Ogbazghi, A.
    Oestreicher, U.
    Palitti, F.
    Pantelias, G.
    Popescu, I.
    Prieto, M. J.
    Roch-Lefevre, S.
    Roessler, U.
    Romm, H.
    Rothkamm, K.
    Sabatier, L.
    Sebastia, N.
    Sommer, S.
    Terzoudi, G.
    Testa, A.
    Thierens, H.
    Trompier, F.
    Turai, I.
    Vandevoorde, C.
    Vaz, P.
    Voisin, P.
    Vral, A.
    Ugletveit, F.
    Wieser, A.
    Woda, C.
    Wojcik, Andrzej
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
    Realising the European network of biodosimetry: RENEB-status quo2015Inngår i: Radiation Protection Dosimetry, ISSN 0144-8420, E-ISSN 1742-3406, Vol. 164, nr 1-2, s. 42-45Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Creating a sustainable network in biological and retrospective dosimetry that involves a large number of experienced laboratories throughout the European Union (EU) will significantly improve the accident and emergency response capabilities in case of a large-scale radiological emergency. A well-organised cooperative action involving EU laboratories will offer the best chance for fast and trustworthy dose assessments that are urgently needed in an emergency situation. To this end, the EC supports the establishment of a European network in biological dosimetry (RENEB). The RENEB project started in January 2012 involving cooperation of 23 organisations from 16 European countries. The purpose of RENEB is to increase the biodosimetry capacities in case of large-scale radiological emergency scenarios. The progress of the project since its inception is presented, comprising the consolidation process of the network with its operational platform, intercomparison exercises, training activities, proceedings in quality assurance and horizon scanning for new methods and partners. Additionally, the benefit of the network for the radiation research community as a whole is addressed.

  • 43. Kulka, U.
    et al.
    Ainsbury, L.
    Atkinson, M.
    Barquinero, J. F.
    Barrios, L.
    Beinke, C.
    Bognar, G.
    Cucu, A.
    Darroudi, F.
    Fattibene, P.
    Gil, O.
    Gregoire, E.
    Hadjidekova, V.
    Haghdoost, Siamak
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för genetik, mikrobiologi och toxikologi.
    Herranz, R.
    Jaworska, A.
    Lindholm, C.
    Mkacher, R.
    Moertl, S.
    Montoro, A.
    Moquet, J.
    Moreno, M.
    Ogbazghi, A.
    Oestreicher, U.
    Palitti, F.
    Pantelias, G.
    Popescu, I.
    Prieto, M. J.
    Romm, H.
    Rothkamm, K.
    Sabatier, L.
    Sommer, S.
    Terzoudi, G.
    Testa, A.
    Thierens, H.
    Trompier, F.
    Turai, I.
    Vandersickel, V.
    Vaz, P.
    Voisin, P.
    Vral, A.
    Ugletveit, F.
    Woda, C.
    Wojcik, Andrzej
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för genetik, mikrobiologi och toxikologi.
    Realising the European Network of Biodosimetry (RENEB)2012Inngår i: Radiation Protection Dosimetry, ISSN 0144-8420, E-ISSN 1742-3406, Vol. 151, nr 4, s. 621-625Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    In Europe, a network for biological dosimetry has been created to strengthen the emergency preparedness and response capabilities in case of a large-scale nuclear accident or radiological emergency. Through the RENEB (Realising the European Network of Biodosimetry) project, 23 experienced laboratories from 16 European countries will establish a sustainable network for rapid, comprehensive and standardised biodosimetry provision that would be urgently required in an emergency situation on European ground. The foundation of the network is formed by five main pillars: (1) the ad hoc operational basis, (2) a basis of future developments, (3) an effective quality-management system, (4) arrangements to guarantee long-term sustainability and (5) awareness of the existence of RENEB. RENEB will thus provide a mechanism for quick, efficient and reliable support within the European radiation emergency management. The scientific basis of RENEB will concurrently contribute to increased safety in the field of radiation protection.

  • 44. Kulka, U.
    et al.
    Wojcik, Andrzej
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
    Di Giorgio, M.
    Wilkins, R.
    Suto, Y.
    Jang, S.
    Quing-Jie, L.
    Jiaxiang, L.
    Ainsbury, E.
    Woda, C.
    Roy, L.
    Li, C.
    Lloyd, D.
    Carr, Z.
    BIODOSIMETRY AND BIODOSIMETRY NETWORKS FOR MANAGING RADIATION EMERGENCY2018Inngår i: Radiation Protection Dosimetry, ISSN 0144-8420, E-ISSN 1742-3406, Vol. 182, nr 1, s. 128-138Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Biological dosimetry enables individual dose reconstruction in the case of unclear or inconsistent radiation exposure situations, especially when a direct measurement of ionizing radiation is not or is no longer possible. To be prepared for large-scale radiological incidents, networking between well-trained laboratories has been identified as a useful approach for provision of the fast and trustworthy dose assessments needed in such circumstances. To this end, various biodosimetry laboratories worldwide have joined forces and set up regional and/or nationwide networks either on a formal or informal basis. Many of these laboratories are also a part of global networks such as those organized by World Health Organization, International Atomic Energy Agency or Global Health Security Initiative. In the present report, biodosimetry networks from different parts of the world are presented, and the partners, activities and cooperation actions are detailed. Moreover, guidance for situational application of tools used for individual dosimetry is given.

  • 45. 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
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
    RENEB - Running the European Network of biological dosimetry and physical retrospective dosimetry2017Inngår i: International Journal of Radiation Biology, ISSN 0955-3002, E-ISSN 1362-3095, Vol. 93, nr 1, s. 2-14Artikkel i tidsskrift (Fagfellevurdert)
    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.

  • 46. Lindholm, Carita
    et al.
    Stricklin, Daniela
    Jaworska, Alicja
    Koivistoinen, Armi
    Paile, Wendla
    Arvidsson, Eva
    Deperas-Standylo, Joanna
    Wojcik, Andrzej
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för genetik, mikrobiologi och toxikologi.
    Premature chromosome condensation (PCC) assay for dose assessment in mass casualty accidents2010Inngår i: Radiation Research, ISSN 0033-7587, E-ISSN 1938-5404, Vol. 173, nr 1, s. 71-8Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The study was undertaken to establish a dose calibration curve for a practical PCC ring assay and to apply it in a simulated mass casualty accident. The PCC assay was validated against the conventional dicentric assay. A linear relationship was established for PCC rings after (60)Co gamma irradiation with doses up to 20 Gy. In the simulated accident experiment, 62 blood samples were analyzed with both the PCC ring assay and the conventional dicentric assay, applying a triage approach. Samples received various uniform and non-uniform (10-40% partial-body) irradiations up to doses of 13 Gy. The results indicated that both assays yielded good dose estimates for the whole-body exposure scenario, although in the lower-dose range (0-6 Gy) dicentric scoring resulted in more accurate whole-body estimates, whereas PCC rings were better in the high-dose range (>6 Gy). Neither assay was successful in identifying partial-body exposures, most likely due to the low numbers of cells scored in the triage mode. In conclusion, the study confirmed that the PCC ring assay is suitable for use as a biodosimeter after whole-body exposure to high doses of radiation. However, there are limitations for its use in the triage of people exposed to high, partial-body doses.

  • 47. Lisowska, Halina
    et al.
    Brehwens, Karl
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
    Zoelzer, Friedo
    Wegierek-Ciuk, Aneta
    Czub, Joanna
    Lankoff, Anna
    Haghdoost, Siamak
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
    Wojcik, Andrzej
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut. Jan Kochanowski University, Poland.
    Effect of hypothermia on radiation-induced micronuclei and delay of cell cycle progression in TK6 cells2014Inngår i: International Journal of Radiation Biology, ISSN 0955-3002, E-ISSN 1362-3095, Vol. 90, nr 4, s. 318-324Artikkel i tidsskrift (Fagfellevurdert)
    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.

  • 48. Lisowska, Halina
    et al.
    Cheng, Lei
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
    Sollazzo, Alice
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
    Lundholm, Lovisa
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
    Wegierek-Ciuk, Aneta
    Sommer, Sylwester
    Lankoff, Anna
    Wojcik, Andrzej
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut. Jan Kochanowski University, Poland.
    Hypothermia modulates the DNA damage response to ionizing radiation in human peripheral blood lymphocytes2018Inngår i: International Journal of Radiation Biology, ISSN 0955-3002, E-ISSN 1362-3095, Vol. 94, nr 6, s. 551-557Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Purpose: Low temperature at exposure has been shown to act in a radioprotective manner at the level of cytogenetic damage. It was suggested to be due to an effective transformation of DNA damage to chromosomal damage at low temperature. The purpose of the study was to analyze the kinetics of aberration formation during the first hours after exposing human peripheral blood lymphocytes to ionizing radiation at 0.8 degrees C and 37 degrees C.Materials and methods: To this end, we applied the technique of premature chromosome condensation. In addition, DNA damage response was analyzed by measuring the levels of phosphorylated DNA damage responsive proteins ATM, DNA-PK and p53 and mRNA levels of the radiation-responsive genes BBC3, FDXR, GADD45A, XPC, MDM2 and CDKN1A.Results: A consistently lower frequency of chromosomal breaks was observed in cells exposed at 0.8 degrees C as compared to 37 degrees C already after 30minutes postexposure. This effect was accompanied by elevated levels of phosphorylated ATM and DNA-PK proteins and a reduced immediate level of phosphorylated p53 and of the responsive genes.Conclusions: Low temperature at exposure appears to promote DNA repair leading to reduced transformation of DNA damage to chromosomal aberrations.

  • 49. Lisowska, Halina
    et al.
    Deperas-Kaminska, Marta
    Haghdoost, Siamak
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för genetik, mikrobiologi och toxikologi.
    Parmryd, Ingela
    Stockholms universitet, Naturvetenskapliga fakulteten, Wenner-Grens institut, Avdelningen för cellbiologi.
    Wojcik, Andrzej
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för genetik, mikrobiologi och toxikologi.
    Radiation-induced DNA damage and repair in human gammadelta and alphabeta T-lymphocytes analysed by the alkaline comet assay.2010Inngår i: Genome integrity, ISSN 2041-9414, Vol. 1, nr 1, s. 8-Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    ABSTRACT: It has been shown by a number of authors that the radiosensitivity of peripheral blood mononuclear cells (PBMC) is higher in cancer patients compared to healthy donors, which is interpreted as a sign of genomic instability. PBMC are composed of different cell subpopulations which are differently radiosensitive and the difference between cancer patients and healthy donors could also be due to different composition of their PBMC pools. Gamma-delta T-lymphocytes play an important role in immunosurveillance and are promising cells for immunotherapy. Their abundance is frequently reduced in cancer patients so should their sensitivity to radiation be lower than that of other T-lymphocytes, this could, at least partly explain the low radiosensitivity of PBMC from healthy individuals compared to cancer patients. The present investigation was carried out to test this. Using the alkaline comet assay we analysed the level of DNA damage and repair in isolated gammadelta T-lymphocytes, pan T-lymphocytes and in total PBMC exposed in vitro to gamma radiation. We found no difference in the level of DNA damage and the capacity of DNA repair between the T cell populations. This is the first study that addresses the question of sensitivity to radiation of gamma-delta T-cells.

  • 50. Lisowska, Halina
    et al.
    Wegierek-Ciuk, Aneta
    Banasik-Nowak, Anna
    Braziewicz, Janusz
    Wojewodzka, Maria
    Wojcik, Andrzej
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för genetik, mikrobiologi och toxikologi.
    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 donors2013Inngår i: International Journal of Radiation Biology, ISSN 0955-3002, E-ISSN 1362-3095, Vol. 89, nr 3, s. 191-199Artikkel i tidsskrift (Fagfellevurdert)
    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.

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