Radiation Effects

Introduction

Protecting and improving human health is at the heart of the biological research being carried out in the Cancer Mechanisms and Biomarkers group. More specifically, we are trying to better understand the mechanisms by which acute or protracted ionising radiation exposure either of natural or medical origin interacts and affects cells and individuals.

Carcinogenesis is the process by which normal cells are transformed into cancer cells. Most cancers are probably initiated by a change in the cell's DNA sequence or an epigenetic modification. Although we know relatively well how radiation-induced DNA damage in cells occurs and the repair pathways involved, it is clear that the rate-limiting step for new approaches for either preventing cancers or detecting them early is the fundamental lack of knowledge about the sequence of the earliest molecular events. One of our aim is understand the role of these events by monitoring the progression of initiated, 'pre-cancerous' cells that acquire critical characteristics in a stepwise fashion sometimes over years after radiation exposure and this can be done in vivo. Another related aim is to discover and validate biomarkers of radiation exposure, toxicity, long term effects and susceptibility using blood samples from healthy donors and cancer patients exposed to radiation from CT scans to radiotherapy treatments. Ultimately, this knowledge is used to support health decisions by the public and policy-makers and will allow individual differences in sensitivity to be taken into account to better protect those at higher risk by regularly monitoring them, decreasing the risk and to intervene to treat cancer earlier.

Networks

National Institute for Health Research, Health Protection Research Units:

  • Chemical and Radiation Threats and Hazards
  • Health Impact of Environmental Hazards
  • The Cancer mechanisms and biomarkers group is actively involved in the Multidisciplinary European Low Dose Initiative (MELODI) and member of the European network of biological dosimetry (RENEB, Realizing the European Network of Biodosimetry, http://reneb.eu/ ) with which we participating to exercises where we receive coded blood samples exposed to unknown doses of ionising radiation which we have to analysed and provide rapid dose estimates.

External funding

Past and current:National Institute of Health Research (NIHR), the European Community seventh framework programme. Project Risk, Stem Cells and Tissue Kinetics - Ionising Radiation (RISK-IR), project VIBRATO (OPERRA), project LEU-TRACK (CONCERT), the NIAID/NIH Centers for Medical Counter Measures Against Radiation Consortium (CMCRC) Program, the US department of Energy, the EMF trust and UK Department of Health.

Areas for potential collaboration

We are continuously seeking potential collaborations with all research establishments (universities, institutes and government organisations) to study the effects of elctromagnetic fields and other agents on behaviour, the circadian clock and brain function.

Contact us

Contact us if you would like to find out more detail or stay informed about a particular field of research. We are always interested in collaborating and are open to partnerships, to drive forward innovation for the benefit of the public.

 

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Last two years publications

  1. Polozov S, Cruz-Garcia L, Badie C. RAPID GENE EXPRESSION BASED DOSE ESTIMATION FOR RADIOLOGICAL EMERGENCIES. Radiat Prot Dosimetry. 2019 Apr 23. pii: ncz053. doi: 10.1093/rpd/ncz053. [Epub ahead of print] PubMed PMID: 31137037.
  2. Mansell E, Zareian N, Malouf C, Kapeni C, Brown N, Badie C, Baird D, Lane J, Ottersbach K, Blair A, Case CP. DNA damage signalling from the placenta to foetal blood as a potential mechanism for childhood leukaemia initiation. Sci Rep. 2019 Mar 13;9(1):4370. doi: 10.1038/s41598-019-39552-0. PubMed PMID: 30867444; PubMed Central PMCID: PMC6416312.
  3. Zyla J, Kabacik S, O'Brien G, Wakil S, Al-Harbi N, Kaprio J, Badie C, Polanska J, Alsbeih G. Combining CDKN1A gene expression and genome-wide SNPs in a twin cohort to gain insight into the heritability of individual radiosensitivity. Funct Integr Genomics. 2019 Jan 31. doi: 10.1007/s10142-019-00658-3. [Epub ahead of print] PubMed PMID: 30706161.
  4. Gault N, Verbiest T, Badie C, Romeo PH, Bouffler S. Hematopoietic stem and progenitor cell responses to low radiation doses - implications for leukemia risk. Int J Radiat Biol. 2019 Jan 17:1-8. doi: 10.1080/09553002.2019.1569777. [Epub ahead of print] PubMed PMID: 30652952.
  5. Verbiest T, Bouffler S, Badie C. No equal opportunity for leukemia initiating cells. Oncotarget. 2018 Dec 14;9(98):37078-37079. doi: 10.18632/oncotarget.26454. eCollection 2018 Dec 14. PubMed PMID: 30647845; PubMed Central PMCID: PMC6324679.
  6. Moquet J, Higueras M, Donovan E, Boyle S, Barnard S, Bricknell C, Sun M, Gothard L, O'Brien G, Cruz-Garcia L, Badie C, Ainsbury E, Somaiah N. Dicentric Dose Estimates for Patients Undergoing Radiotherapy in the RTGene Study to Assess Blood Dosimetric Models and the New Bayesian Method for Gradient Exposure. Radiat Res. 2018 Sep 20. doi: 10.1667/RR15116.1. [Epub ahead of print] PubMed PMID: 30234457; PubMed Central PMCID: PMC6426678.
  7. Cuceu C, Colicchio B, Jeandidier E, Junker S, Plassa F, Shim G, Mika J, Frenzel M, Al Jawhari M, Hempel WM, O'Brien G, Lenain A, Morat L, Girinsky T, Dieterlen A, Polanska J, Badie C, Carde P, M'Kacher R. Independent Mechanisms Lead to Genomic Instability in Hodgkin Lymphoma: Microsatellite or Chromosomal Instability. Cancers (Basel). 2018 Jul 13;10(7). pii: E233. doi:10.3390/cancers10070233. Erratum in: Cancers (Basel). 2019 May 30;11(6):. PubMed PMID: 30011886; PubMed Central PMCID: PMC6071189.
  8. Karabulutoglu M, Finnon R, Imaoka T, Friedl AA, Badie C. Influence of diet and metabolism on hematopoietic stem cells and leukemia development following ionizing radiation exposure. Int J Radiat Biol. 2019 Apr;95(4):452-479. doi:10.1080/09553002.2018.1490042. Epub 2018 Sep 24. PubMed PMID: 29932783.
  9. Cruz-Garcia L, O'Brien G, Donovan E, Gothard L, Boyle S, Laval A, Testard I, Ponge L, Woźniak G, Miszczyk L, Candéias SM, Ainsbury E, Widlak P, Somaiah N, Badie C. Influence of Confounding Factors on Radiation Dose Estimation Using In Vivo Validated Transcriptional Biomarkers. Health Phys. 2018 Jul;115(1):90-101. doi: 10.1097/HP.0000000000000844. PubMed PMID: 29787434; PubMed Central PMCID:PMC5967635.
  10. Verbiest T, Finnon R, Brown N, Cruz-Garcia L, Finnon P, O'Brien G, Ross E, Bouffler S, Scudamore CL, Badie C. Tracking preleukemic cells in vivo to reveal the sequence of molecular events in radiation leukemogenesis. Leukemia. 2018 Jun;32(6):1435-1444. doi: 10.1038/s41375-018-0085-1. Epub 2018 Mar 3. PubMed PMID: 29556020; PubMed Central PMCID: PMC5990525.
  11. Hall J, Jeggo PA, West C, Gomolka M, Quintens R, Badie C, Laurent O, Aerts A, Anastasov N, Azimzadeh O, Azizova T, Baatout S, Baselet B, Benotmane MA, Blanchardon E, Guéguen Y, Haghdoost S, Harms-Ringhdahl M, Hess J, Kreuzer M, Laurier D, Macaeva E, Manning G, Pernot E, Ravanat JL, Sabatier L, Tack K, Tapio S, Zitzelsberger H, Cardis E. Ionizing radiation biomarkers in epidemiological studies - An update. Mutat Res. 2017 Jan - Mar;771:59-84. doi:10.1016/j.mrrev.2017.01.001. Epub 2017 Jan 16. Review. PubMed PMID: 28342453.
  12. Manning G, Tichý A, Sirák I, Badie C. Radiotherapy-Associated Long-term Modification of Expression of the Inflammatory Biomarker Genes ARG1, BCL2L1, and MYC. Front Immunol. 2017 Apr 10;8:412. doi: 10.3389/fimmu.2017.00412. eCollection 2017. PubMed PMID: 28443095; PubMed Central PMCID: PMC5385838.
  13. Candéias SM, Mika J, Finnon P, Verbiest T, Finnon R, Brown N, Bouffler S, Polanska J, Badie C. Low-dose radiation accelerates aging of the T-cell receptor repertoire in CBA/Ca mice. Cell Mol Life Sci. 2017 Dec;74(23):4339-4351. doi:10.1007/s00018-017-2581-2. Epub 2017 Jun 30. PubMed PMID: 28667356.
  14. Port M, Majewski M, Herodin F, Valente M, Drouet M, Forcheron F, Tichy A, Sirak I, Zavrelova A, Malkova A, Becker BV, Veit DA, Waldeck S, Badie C, O'Brien G, Christiansen H, Wichmann J, Eder M, Beutel G, Vachelova J, Doucha-Senf S, Abend M. Validating Baboon Ex Vivo and In Vivo Radiation-Related Gene Expression with Corresponding Human Data. Radiat Res. 2018 Apr;189(4):389-398. doi:10.1667/RR14958.1. Epub 2018 Jan 26. PubMed PMID: 29373091.
  15. O'Brien G, Cruz-Garcia L, Majewski M, Grepl J, Abend M, Port M, Tichý A, Sirak I, Malkova A, Donovan E, Gothard L, Boyle S, Somaiah N, Ainsbury E, Ponge L, Slosarek K, Miszczyk L, Widlak P, Green E, Patel N, Kudari M, Gleeson F, Vinnikov V, Starenkiy V, Artiukh S, Vasyliev L, Zaman A, Badie C. FDXR is a biomarker of radiation exposure in vivo. Sci Rep. 2018 Jan 12;8(1):684. doi:10.1038/s41598-017-19043-w. PubMed PMID: 29330481; PubMed Central PMCID:PMC5766591.
  16. Tichý A, Kabacik S, O'Brien G, Pejchal J, Sinkorova Z, Kmochova A, Sirak I, Malkova A, Beltran CG, Gonzalez JR, Grepl J, Majewski M, Ainsbury E, Zarybnicka L, Vachelova J, Zavrelova A, Davidkova M, Markova Stastna M, Abend M, Pernot E, Cardis E, Badie C. The first in vivo multiparametric comparison of different radiation exposure biomarkers in human blood. PLoS One. 2018 Feb 23;13(2):e0193412. doi: 10.1371/journal.pone.0193412. eCollection 2018. PubMed PMID: 29474504; PubMed Central PMCID: PMC5825084.
  17. Candéias SM, Kabacik S, Olsen AK, Eide DM, Brede DA, Bouffler S, Badie C. Ionizing radiation does not impair the mechanisms controlling genetic stability during T cell receptor gene rearrangement in mice. Int J Radiat Biol. 2018 Apr;94(4):357-365. doi: 10.1080/09553002.2018.1439195. Epub 2018 Feb 27. PubMed PMID: 29431562.
  18. Tom Verbiest, Rosemary Finnon, Natalie Brown, Lourdes Cruz-Garcia, Paul Finnon, Grainne O''Brien, Eleanor Ross, Simon Bouffler, Cheryl L. Scudamore, Christophe Badie Tracking preleukemic cells in vivo to reveal the sequence of molecular events in radiation leukemogenesis Leukemia accepted
  19. Tichy A, Kabacik S, O'Brien G, Pejchal J, Sinkorova Z, Kmochova A, Sirak I, Malkova A, Beltran CG, Gonzalez JR, Grepl J, Majewski M, Ainsbury E, Zarybnicka L, Vachelova J, Zavrelova A, Davidkova M, Markova Stastna M, Abend M, Pernot E, Cardis E, Badie C. The first in vivo multiparametric comparison of different radiation exposure biomarkers in human blood. PLoS One. 2018 Feb 23;13(2):e0193412. doi: 10.1371/journal.pone.0193412. eCollection 2018. PubMed PMID: 29474504.
  20. Port M, Majewski M, Herodin F, Valente M, Drouet M, Forcheron F, Tichy A, Sirak I, Zavrelova A, Malkova A, Becker BV, Veit DA, Waldeck S, Badie C, O'Brien G, Christiansen H, Wichmann J, Eder M, Beutel G, Vachelova J, Doucha-Senf S, Abend M. Validating Baboon Ex Vivo and In Vivo Radiation-Related Gene Expression with Corresponding Human Data. Radiat Res. 2018 Jan 26. doi: 10.1667/RR14958.1. [Epub ahead of print] PubMed PMID: 29373091.
  21. Candéias SM, Kabacik S, Olsen AK, Eide DM, Brede DA, Bouffler S, Badie C. Ionizing radiation does not impair the mechanisms controlling genetic stability during T cell receptor gene rearrangement in mice. Int J Radiat Biol. 2018 Feb 27:1-9. doi: 10.1080/09553002.2018.1439195. [Epub ahead of print] PubMed PMID: 29431562.
  22. O'Brien G, Cruz-Garcia L, Majewski M, Grepl J, Abend M, Port M, Tichý A, Sirak I, Malkova A, Donovan E, Gothard L, Boyle S, Somaiah N, Ainsbury E, Ponge L, Slosarek K, Miszczyk L, Widlak P, Green E, Patel N, Kudari M, Gleeson F, Vinnikov V, Starenkiy V, Artiukh S, Vasyliev L, Zaman A, Badie C. FDXR is a biomarker of radiation exposure in vivo. Sci Rep. 2018 Jan 12;8(1):684. doi: 10.1038/s41598-017-19043-w. PubMed PMID: 29330481; PubMed Central PMCID: PMC5766591.
  23. Candéias SM, Mika J, Finnon P, Verbiest T, Finnon R, Brown N, Bouffler S, Polanska J, Badie C. Low-dose radiation accelerates aging of the T-cell receptor repertoire in CBA/Ca mice. Cell Mol Life Sci. 2017 Dec;74(23):4339-4351. doi: 10.1007/s00018-017-2581-2. Epub 2017 Jun 30. PubMed PMID: 28667356.
  24. Manning G, Tichý A, Sirák I, Badie C. Radiotherapy-Associated Long-term Modification of Expression of the Inflammatory Biomarker Genes ARG1, BCL2L1, and MYC. Front Immunol. 2017 Apr 10;8:412. doi: 10.3389/fimmu.2017.00412. eCollection 2017. PubMed PMID: 28443095; PubMed Central PMCID: PMC5385838.
  25. Hall J, Jeggo PA, West C, Gomolka M, Quintens R, Badie C, Laurent O, Aerts A, Anastasov N, Azimzadeh O, Azizova T, Baatout S, Baselet B, Benotmane MA, Blanchardon E, Guéguen Y, Haghdoost S, Harms-Ringhdahl M, Hess J, Kreuzer M, Laurier D, Macaeva E, Manning G, Pernot E, Ravanat JL, Sabatier L, Tack K, Tapio S, Zitzelsberger H, Cardis E. Ionizing radiation biomarkers in epidemiological studies - An update. Mutat Res. 2017 Jan - Mar;771:59-84. doi: 10.1016/j.mrrev.2017.01.001. Epub 2017 Jan 16. Review. PubMed PMID: 28342453.
  26. Guéguen Y, Roy L, Hornhardt S, Badie C, Hall J, Baatout S, Pernot E, Tomasek L, Laurent O, Ebrahimian T, Ibanez C, Grison S, Kabacik S, Laurier D, Gomolka M. Biomarkers for Uranium Risk Assessment for the Development of the CURE (Concerted Uranium Research in Europe) Molecular Epidemiological Protocol. Radiat Res. 2017 Jan;187(1):107-127. doi: 10.1667/RR14505.1. Epub 2016 Dec 30. Review. PubMed PMID: 28036235.
  27. Patel A, Anderson J, Kraft D, Finnon R, Finnon P, Scudamore CL, Manning G, Bulman R, Brown N, Bouffler S, O'Neill P, Badie C. The Influence of the CTIP Polymorphism, Q418P, on Homologous Recombination and Predisposition to Radiation-Induced Tumorigenesis (mainly rAML) in Mice. Radiat Res. 2016 Dec;186(6):638-649. doi: 10.1667/RR14495.1. Epub 2016 Nov 21. PubMed PMID: 27869555.
  28. Verbiest T, Finnon R, Brown N, Finnon P, Bouffler S, Badie C. NOD Scid Gamma Mice Are Permissive to Allogeneic HSC Transplantation without Prior Conditioning. Int J Mol Sci. 2016 Nov 7;17(11). pii: E1850. PubMed PMID: 27827995; PubMed Central PMCID: PMC5133850.
  29. Badie C, Blachowicz A, Barjaktarovic Z, Finnon R, Michaux A, Sarioglu H, Brown N, Manning G, Benotmane MA, Tapio S, Polanska J, Bouffler SD. Transcriptomic and proteomic analysis of mouse radiation-induced acute myeloid leukaemia (AML). Oncotarget. 2016 Jun 28;7(26):40461-40480. doi: 10.18632/oncotarget.9626. PubMed PMID: 27250028; PubMed Central PMCID: PMC5130020.
  30. Kulka U, Abend M, Ainsbury E, Badie C, Barquinero JF, Barrios L, Beinke C, Bortolin E, Cucu A, De Amicis A, Domínguez I, Fattibene P, Frøvig AM, Gregoire E, Guogyte K, Hadjidekova V, Jaworska A, Kriehuber R, Lindholm C, Lloyd D, Lumniczky K, Lyng F, Meschini R, Mörtl S, Della Monaca S, Monteiro Gil O, Montoro A, Moquet J, Moreno M, Oestreicher U, Palitti F, Pantelias G, Patrono C, Piqueret-Stephan L, Port M, Prieto MJ, Quintens R, Ricoul M, Romm H, Roy L, Sáfrány G, Sabatier L, Sebastià N, Sommer S, Terzoudi G, Testa A, Thierens H, Turai I, Trompier F, Valente M, Vaz P, Voisin P, Vral A, Woda C, Zafiropoulos D, Wojcik A. RENEB - Running the European Network of biological dosimetry and physical retrospective dosimetry. Int J Radiat Biol. 2017 Jan;93(1):2-14. doi: 10.1080/09553002.2016.1230239. Epub 2016 Oct 6. PubMed PMID: 27707245.
  31. Manning G, Macaeva E, Majewski M, Kriehuber R, Brzóska K, Abend M, Doucha-Senf S, Oskamp D, Strunz S, Quintens R, Port M, Badie C. Comparable dose estimates of blinded whole blood samples are obtained independently of culture conditions and analytical approaches. Second RENEB gene expression study. Int J Radiat Biol. 2017 Jan;93(1):87-98. doi: 10.1080/09553002.2016.1227105. Epub 2016 Sep 14. PubMed PMID: 27626709.
  32. Behjati S, Gundem G, Wedge DC, Roberts ND, Tarpey PS, Cooke SL, Van Loo P, Alexandrov LB, Ramakrishna M, Davies H, Nik-Zainal S, Hardy C, Latimer C, Raine KM, Stebbings L, Menzies A, Jones D, Shepherd R, Butler AP, Teague JW, Jorgensen M, Khatri B, Pillay N, Shlien A, Futreal PA, Badie C; ICGC Prostate Group, McDermott U, Bova GS, Richardson AL, Flanagan AM, Stratton MR, Campbell PJ. Mutational signatures of ionizing radiation in second malignancies. Nat Commun. 2016 Sep 12;7:12605. doi: 10.1038/ncomms12605. PubMed PMID: 27615322; PubMed Central PMCID: PMC5027243.
  33. Ainsbury E, Badie C, Barnard S, Manning G, Moquet J, Abend M, Antunes AC, Barrios L, Bassinet C, Beinke C, Bortolin E, Bossin L, Bricknell C, Brzoska K, Buraczewska I, Castaño CH, Čemusová Z, Christiansson M, Cordero SM, Cosler G, Monaca SD, Desangles F, Discher M, Dominguez I, Doucha-Senf S, Eakins J, Fattibene P, Filippi S, Frenzel M, Georgieva D, Gregoire E, Guogyte K, Hadjidekova V, Hadjiiska L, Hristova R, Karakosta M, Kis E, Kriehuber R, Lee J, Lloyd D, Lumniczky K, Lyng F, Macaeva E, Majewski M, Vanda Martins S, McKeever SW, Meade A, Medipally D, Meschini R, M'kacher R, Gil OM, Montero A, Moreno M, Noditi M, Oestreicher U, Oskamp D, Palitti F, Palma V, Pantelias G, Pateux J, Patrono C, Pepe G, Port M, Prieto MJ, Quattrini MC, Quintens R, Ricoul M, Roy L, Sabatier L, Sebastià N, Sholom S, Sommer S, Staynova A, Strunz S, Terzoudi G, Testa A, Trompier F, Valente M, Hoey OV, Veronese I, Wojcik A, Woda C. Integration of new biological and physical retrospective dosimetry methods into EU emergency response plans - joint RENEB and EURADOS inter-laboratory comparisons. Int J Radiat Biol. 2017 Jan;93(1):99-109. doi: 10.1080/09553002.2016.1206233. Epub 2016 Jul 20. Erratum in: Int J Radiat Biol. 2017 Jan;93(1):x. PubMed PMID: 27437830.
  34. Laurent O, Gomolka M, Haylock R, Blanchardon E, Giussani A, Atkinson W, Baatout S, Bingham D, Cardis E, Hall J, Tomasek L, Ancelet S, Badie C, Bethel G, Bertho JM, Bouet S, Bull R, Challeton-de Vathaire C, Cockerill R, Davesne E, Ebrahimian T, Engels H, Gillies M, Grellier J, Grison S, Gueguen Y, Hornhardt S, Ibanez C, Kabacik S, Kotik L, Kreuzer M, Lebacq AL, Marsh J, Nosske D, O'Hagan J, Pernot E, Puncher M, Rage E, Riddell T, Roy L, Samson E, Souidi M, Turner MC, Zhivin S, Laurier D. Concerted Uranium Research in Europe (CURE): toward a