50 results on '"Devic C"'
Search Results
2. CO10.1 - PAPY THEO - Aide à la récupération de données pour les essais cliniques
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Devic, C., primary, Schiappa, R., additional, Ferrari, V., additional, Chateau, Y., additional, and Chamorey, E., additional
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- 2023
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3. Le phénomène d’hypersensibilité aux faibles doses : une énigme de la radiobiologie enfin résolue ?
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Devic, C., Bodgi, L., Granzotto, A., Ferlazzo, M., Sonzogni, L., Bourguignon, M., and Foray, N.
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- 2016
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4. Biologie des radiations : avancées majeures et perspectives pour la radiothérapie
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Joubert, A., Vogin, G., Devic, C., Granzotto, A., Viau, M., Maalouf, M., Thomas, C., Colin, C., and Foray, N.
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- 2011
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5. Multicentric comparative study of dose indexes using an “in vivo” optical fiber detection system
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Popotte, C., primary, Devic, C., additional, Munier, M., additional, Moreno, R., additional, Rousseau, H., additional, Perlongo, S., additional, Pilleul, F., additional, and Paul, D., additional
- Published
- 2021
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6. Nano-Se° and selenite ions impact on DNA double-strand breaks induction, repair and signaling
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Charlet, L, primary, Bochot, C, additional, Bardelli, F, additional, Foray, N, additional, Faycal, C, additional, Ferlazzo, M, additional, Devic, C, additional, Granzotto, A, additional, and Bodgi, L, additional
- Published
- 2013
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7. OD155 - Multicentric comparative study of dose indexes using an “in vivo” optical fiber detection system
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Popotte, C., Devic, C., Munier, M., Moreno, R., Rousseau, H., Perlongo, S., Pilleul, F., and Paul, D.
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- 2021
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8. Projet RACKHAM : étude de la radiosensibilité des patients atteints de neurofibromatose de type 1 (NF1), résultats finaux
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Combemale, P., primary, Devic, C., additional, Ferlazzo, M., additional, Sonzogni, L., additional, Granzoto, A., additional, Pinson, S., additional, and Foray, N., additional
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- 2017
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9. Étude la radiosensibilité des patients atteints de neurofibromatose de type 1 : projet Rackham
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Combemale, P., primary, Devic, C., additional, Ferlazzo, M., additional, Sonzogni, L., additional, Granzotto, A., additional, Pinson, S., additional, and Foray, N., additional
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- 2016
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10. Effets de répétitions de doses d’irradiation et réparation de l’ADN : importance du facteur individuel et de l’intervalle de temps entre les doses
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Viau, M., primary, Perez, A.-F., additional, Bodgi, L., additional, Devic, C., additional, Granzotto, A., additional, Ferlazzo, M.L., additional, Bourguignon, M., additional, Puisieux, A., additional, Lacornerie, T., additional, Lartigau, É., additional, Lagrange, J.-L., additional, and Foray, N., additional
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- 2016
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11. Prise en charge des atteintes craniofaciales de la neurofibromatose de type 1
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Bachelet, J.T., primary, Combemale, P., additional, Devic, C., additional, Foray, N., additional, Jouanneau, E., additional, and Breton, P., additional
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- 2015
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12. Characterization of residual stresses in a composite curved sandwich beam
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Casari, Pascal, Devic, C., Gornet, Laurent, Institut de Recherche en Génie Civil et Mécanique (GeM), Université de Nantes - UFR des Sciences et des Techniques (UN UFR ST), and Université de Nantes (UN)-Université de Nantes (UN)-École Centrale de Nantes (ECN)-Centre National de la Recherche Scientifique (CNRS)
- Subjects
[SPI.MECA]Engineering Sciences [physics]/Mechanics [physics.med-ph] ,[SPI.MAT]Engineering Sciences [physics]/Materials - Abstract
Residual stresses are of great importance in ensuring geometrical stability of sandwich structures. Indeed, creep phenomena occur after manufacturing and can lead to unexpected deformations in sandwich shells. In order to assess these, a first experiment has been performed on the shell to provide an order of magnitude indication of the residual stresses by means of cutting to release the stresses. This approach is then extended to a sandwich beam extracted from the shell. This is completed by the thermo-mechanical characterisation of the skins in order to provide the properties required for modelling. Finally, a three-dimensional finite element model is presented, which includes both thermal and mechanical behaviour. Comparisons are made between the model and a heating experiment on the sandwich beam. The thermomechanical response of the beam is found to be particularly sensitive to the thermal properties of the constituents.
- Published
- 2003
13. MRE11 and H2AX biomarkers in the response to low-dose exposure: balance between individual susceptibility to radiosensitivity and to genomic instability
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Colin, C., primary, Granzotto, A., additional, Devic, C., additional, Massart, C., additional, Viau, M., additional, Vogin, G., additional, Maalouf, M., additional, Joubert, A., additional, and Foray, N., additional
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- 2011
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14. GENSTYLE: exploration and analysis of DNA sequences with genomic signature
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Fertil, B., primary, Massin, M., additional, Lespinats, S., additional, Devic, C., additional, Dumee, P., additional, and Giron, A., additional
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- 2005
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15. OCARI: Optimization of communication for Ad hoc reliable industrial networks.
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Tuan Dang and Devic, C.
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- 2008
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16. Industrial Wireless Technologies: applications for the electrical utilities.
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Carcelle, X., Tuan Dang, and Devic, C.
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- 2006
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17. Organisation fonctionnelle du tissu producteur de l'Hevea brasiliensis
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Hébant, C., Devic, C., and De Fay, Elisabeth
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Cambium ,Biosynthèse ,laticifère ,F50 - Anatomie et morphologie des plantes ,Hevea brasiliensis ,Bois ,Anatomie végétale ,Écorce ,Phloème ,Faisceau vasculaire - Abstract
Dans l'écorce de l'Hevea brasiliensis, la zone de phloème conducteur, qui est la voie de transport sur de longues distances des assimilats est réduite à une étroite bande de 0, 2 à 1mm de large, contiguë au cambium. La majorité des manchons de laticifères sont localisés dans des parties plus externes de l'écorce et par conséquent en dehors de cette bande. Un transport horizontal au travers des rayons libériens apparait essentiel pour l'approvisionnement des laticifères en métabolites nécessaires à la biosynthèse du caoutchouc. Les réserves notamment l'amidon, des cellules parenchymateuses du bois paraissent également susceptibles de contribuer à l'alimentation des laticifères, par l'intermédiaire des rayons vasculaires qui traversent le cambium
- Published
- 1981
18. Nano-Se° and selenite ions impact on DNA double-strand breaks induction, repair and signaling: Structural, chemical and biological features
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Charlet, L., Bochot, C., Bardelli, F., Nicolas Foray, Abou Faycal, C., Ferlazzo, M., Devic, C., Granzotto, A., and Bodgi, L.
19. COVID-19 and vaccination impact on radiology departments provided by Dose Archiving and Communication System.
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Meyrignac O, Devic C, Munier M, Rius E, Crézé M, and Moreno R
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- Humans, Radiation Dosage, Retrospective Studies, Pandemics prevention & control, Communication, COVID-19 epidemiology, COVID-19 prevention & control, Radiology
- Abstract
Objectives: To study the impact of COVID-19 on chest CT practice during the different waves using Dose Archiving and Communication System (DACS)., Methods: Retrospective study including data from 86,136 chest CT acquisitions from 27 radiology centers (15 private; 12 public) between January 1, 2020, and October 13, 2021, using a centralized DACS. Daily chest CT activity and dosimetry information such as dose length product (DLP), computed tomography dose index (CTDI), and acquisition parameters were collected. Pandemic indicators (daily tests performed, incidence, and hospital admissions) and vaccination rates were collected from a governmental open-data platform. Descriptive statistics and correlation analysis were performed., Results: For the first two waves, strong positive and significant correlations were found between all pandemic indicators and total chest CT activity, as high as R = 0.7984 between daily chest CT activity and hospital admissions during the second wave (p < 0.0001). We found differences between public hospitals and private imaging centers during the first wave, with private centers demonstrating a negative correlation between daily chest CT activity and hospital admissions (-0.2819, p = 0.0019). Throughout the third wave, simultaneously with the rise of vaccination rates, total chest CT activity decreased with significant negative correlations with pandemic indicators, such as R = -0.7939 between daily chest CTs and daily incidence (p < 0.0001). Finally, less than 5% of all analyzed chest CTs could be considered as low dose., Conclusions: During the first waves, COVID-19 had a strong impact on chest CT practice which was lost with the arrival of vaccination. Low-dose protocols remained marginal., Key Points: • There was a significant correlation between the number of daily chest CTs and pandemic indicators throughout the first two waves. It was lost during the third wave due to vaccination arrival. • Differences were observed between public and private centers, especially during the first wave, less during the second, and were lost during the third. • During the first three waves of COVID-19 pandemic, few CT helical acquisitions could be considered as low dose with only 3.8% of the acquisitions according to CTDIvol and 4.3% according to DLP., (© 2023. The Author(s), under exclusive licence to European Society of Radiology.)
- Published
- 2023
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20. Toward an Early Diagnosis for Alzheimer's Disease Based on the Perinuclear Localization of the ATM Protein.
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Berthel E, Pujo-Menjouet L, Le Reun E, Sonzogni L, Al-Choboq J, Chekroun A, Granzotto A, Devic C, Ferlazzo ML, Pereira S, Bourguignon M, and Foray N
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- Humans, Ataxia Telangiectasia Mutated Proteins metabolism, DNA Breaks, Double-Stranded, Cell Nucleus metabolism, DNA Repair, Alzheimer Disease diagnosis, Alzheimer Disease metabolism
- Abstract
Alzheimer's disease (AD) is the most common neurodegenerative dementia, for which the molecular origins, genetic predisposition and therapeutic approach are still debated. In the 1980s, cells from AD patients were reported to be sensitive to ionizing radiation. In order to examine the molecular basis of this radiosensitivity, the ATM-dependent DNA double-strand breaks (DSB) signaling and repair were investigated by applying an approach based on the radiation-induced ataxia telangiectasia-mutated (ATM) protein nucleoshuttling (RIANS) model. Early after irradiation, all ten AD fibroblast cell lines tested showed impaired DSB recognition and delayed RIANS. AD fibroblasts specifically showed spontaneous perinuclear localization of phosphorylated ATM (pATM) forms. To our knowledge, such observation has never been reported before, and by considering the role of the ATM kinase in the stress response, it may introduce a novel interpretation of accelerated aging. Our data and a mathematical approach through a brand-new model suggest that, in response to a progressive and cumulative stress, cytoplasmic ATM monomers phosphorylate the APOE protein (pAPOE) close to the nuclear membrane and aggregate around the nucleus, preventing their entry in the nucleus and thus the recognition and repair of spontaneous DSB, which contributes to the aging process. Our findings suggest that pATM and/or pAPOE may serve as biomarkers for an early reliable diagnosis of AD on any fibroblast sample.
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- 2023
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21. Quantitative Correlations between Radiosensitivity Biomarkers Show That the ATM Protein Kinase Is Strongly Involved in the Radiotoxicities Observed after Radiotherapy.
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Le Reun E, Bodgi L, Granzotto A, Sonzogni L, Ferlazzo ML, Al-Choboq J, El-Nachef L, Restier-Verlet J, Berthel E, Devic C, Bouchet A, Bourguignon M, and Foray N
- Subjects
- Ataxia Telangiectasia Mutated Proteins metabolism, Biomarkers metabolism, Cell Survival radiation effects, DNA Repair, Fibroblasts metabolism, Humans, Protein Kinases metabolism, Radiation Tolerance radiation effects
- Abstract
Tissue overreactions (OR), whether called adverse effects, radiotoxicity, or radiosensitivity reactions, may occur during or after anti-cancer radiotherapy (RT). They represent a medical, economic, and societal issue and raise the question of individual response to radiation. To predict and prevent them are among the major tasks of radiobiologists. To this aim, radiobiologists have developed a number of predictive assays involving different cellular models and endpoints. To date, while no consensus has been reached to consider one assay as the best predictor of the OR occurrence and severity, radiation oncologists have proposed consensual scales to quantify OR in six different grades of severity, whatever the organ/tissue concerned and their early/late features. This is notably the case with the Common Terminology Criteria for Adverse Events (CTCAE). Few radiobiological studies have used the CTCAE scale as a clinical endpoint to evaluate the statistical robustness of the molecular and cellular predictive assays in the largest range of human radiosensitivity. Here, by using 200 untransformed skin fibroblast cell lines derived from RT-treated cancer patients eliciting OR in the six CTCAE grades range, correlations between CTCAE grades and the major molecular and cellular endpoints proposed to predict OR (namely, cell survival at 2 Gy (SF2), yields of micronuclei, recognized and unrepaired DSBs assessed by immunofluorescence with γH2AX and pATM markers) were examined. To our knowledge, this was the first time that the major radiosensitivity endpoints were compared together with the same cohort and irradiation conditions. Both SF2 and the maximal number of pATM foci reached after 2 Gy appear to be the best predictors of the OR, whatever the CTCAE grades range. All these major radiosensitivity endpoints are mathematically linked in a single mechanistic model of individual response to radiation in which the ATM kinase plays a major role.
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- 2022
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22. Influence of cellular models and individual factor in the biological response to head CT scan exams.
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Devic C, Bodgi L, Sonzogni L, Pilleul F, Ribot H, De Charry C, Le Moigne F, Paul D, Carbillet F, Munier M, and Foray N
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- Ataxia Telangiectasia Mutated Proteins genetics, Ataxia Telangiectasia Mutated Proteins metabolism, Fibroblasts metabolism, Humans, Tomography, X-Ray Computed, DNA Breaks, Double-Stranded, DNA Repair
- Abstract
Background: While computed tomography (CT) exams are the major cause of medical exposure to ionising radiation, the radiation-induced risks must be documented. We investigated the impact of the cellular models and individual factor on the deoxyribonucleic acid double-strand breaks (DSB) recognition and repair in human skin fibroblasts and brain astrocytes exposed to current head CT scan conditions., Method: Nine human primary fibroblasts and four human astrocyte cell lines with different levels of radiosensitivity/susceptibility were exposed to a standard head CT scan exam using adapted phantoms. Cells were exposed to a single-helical (37.4 mGy) and double-helical (37.4 mGy + 5 min + 37.4 mGy) examination. DSB signalling and repair was assessed through anti-γH2AX and anti-pATM immunofluorescence., Results: Head CT scan induced a significant number of γH2AX and pATM foci. The kinetics of both biomarkers were found strongly dependent on the individual factor. Particularly, in cells from radiosensitive/susceptible patients, DSB may be significantly less recognised and/or repaired, whatever the CT scan exposure conditions. Similar conclusions were reached with astrocytes., Conclusions: Our results highlight the importance of both individual and tissue factors in the recognition and repair of DSB after current head CT scan exams. Further investigations are needed to better define the radiosensitivity/susceptibility of individual humans., (© 2022. The Author(s) under exclusive licence to European Society of Radiology.)
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- 2022
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23. Influence of cellular models and individual factor in the biological response to chest CT scan exams.
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Devic C, Bodgi L, Sonzogni L, Pilleul F, Ribot H, Charry C, Le Moigne F, Paul D, Carbillet F, Munier M, and Foray N
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- Ataxia Telangiectasia Mutated Proteins genetics, Ataxia Telangiectasia Mutated Proteins metabolism, DNA Repair, Humans, Tomography, X-Ray Computed, DNA Breaks, Double-Stranded, Histones metabolism, Histones radiation effects
- Abstract
Background: While computed tomography (CT) exams are the major cause of medical exposure to ionising radiation, there is increasing evidence that the potential radiation-induced risks must be documented. We investigated the impact of cellular models and individual factor on the deoxyribonucleic acid double-strand breaks (DSB) recognition and repair in human fibroblasts and mammary epithelial cells exposed to current chest CT scan conditions., Method: Twelve human primary fibroblasts and four primary human mammary epithelial cell lines with different levels of radiosensitivity/susceptibility were exposed to a standard chest CT scan exam using adapted phantoms. Cells were exposed to a single helical irradiation (14.4 mGy) or to a topogram followed, after 1 min, by one single helical examination (1.1 mGy + 14.4 mGy). DSB signalling and repair was assessed through anti-γH2AX and anti-pATM immunofluorescence., Results: Chest CT scan induced a significant number of γH2AX and pATM foci. The kinetics of both biomarkers were found strongly dependent on the individual factor. The topogram may also influence the biological response of radiosensitive/susceptible fibroblasts to irradiation. Altogether, our findings show that a chest CT scan exam may result in 2 to 3 times more unrepaired DSB in cells from radiosensitive/susceptible patients., Conclusions: Both individual and tissue factors in the recognition and repair of DSB after current CT scan exams are important. Further investigations are needed to better define the radiosensitivity/susceptibility of individual humans., (© 2022. The Author(s) under exclusive licence to European Society of Radiology.)
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- 2022
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24. Individual Response to Radiation of Individuals with Neurofibromatosis Type I: Role of the ATM Protein and Influence of Statins and Bisphosphonates.
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Combemale P, Sonzogni L, Devic C, Bencokova Z, Ferlazzo ML, Granzotto A, Burlet SF, Pinson S, Amini-Adle M, Al-Choboq J, Bodgi L, Bourguignon M, Balosso J, Bachelet JT, and Foray N
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- Cell Line, Cell Survival drug effects, DNA Breaks, Double-Stranded drug effects, DNA Breaks, Double-Stranded radiation effects, DNA Repair drug effects, Fibroblasts drug effects, Fibroblasts metabolism, Humans, Neurofibromatosis 1 metabolism, Ataxia Telangiectasia Mutated Proteins metabolism, Cell Survival radiation effects, DNA Repair radiation effects, Diphosphonates pharmacology, Fibroblasts radiation effects, Hydroxymethylglutaryl-CoA Reductase Inhibitors pharmacology, Neurofibromatosis 1 radiotherapy, Radiation, Ionizing
- Abstract
Neurofibromatosis type 1 (NF1) is a disease characterized by high occurrence of benign and malignant brain tumours and caused by mutations of the neurofibromin protein. While there is an increasing evidence that NF1 is associated with radiosensitivity and radiosusceptibility, few studies have dealt with the molecular and cellular radiation response of cells from individuals with NF1. Here, we examined the ATM-dependent signalling and repair pathways of the DNA double-strand breaks (DSB), the key-damage induced by ionizing radiation, in skin fibroblast cell lines from 43 individuals with NF1. Ten minutes after X-rays irradiation, quiescent NF1 fibroblasts showed abnormally low rate of recognized DSB reflected by a low yield of nuclear foci formed by phosphorylated H2AX histones. Irradiated NF1 fibroblasts also presented a delayed radiation-induced nucleoshuttling of the ATM kinase (RIANS), potentially due to a specific binding of ATM to the mutated neurofibromin in cytoplasm. Lastly, NF1 fibroblasts showed abnormally high MRE11 nuclease activity suggesting a high genomic instability after irradiation. A combination of bisphosphonates and statins complemented these impairments by accelerating the RIANS, increasing the yield of recognized DSB and reducing genomic instability. Data from NF1 fibroblasts exposed to radiation in radiotherapy and CT scan conditions confirmed that NF1 belongs to the group of syndromes associated with radiosensitivity and radiosusceptibility., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
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- 2022
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25. Characterization of an Innovative Detector Based on Scintillating Fiber for Personalized Computed Tomography Dosimetry.
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Devic C, Plagnard J, and Munier M
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- Plastics, Radiometry, Tomography, X-Ray Computed
- Abstract
For technical and radioprotection reasons, it has become essential to develop new dosimetric tools adapted to the specificities of computed tomography (CT) to ensure precise and efficient dosimetry since the current standards are not suitable for clinical use and for new CT technological evolution. Thanks to its many advantages, plastic scintillating fibers (PSF) is a good candidate for more accurate and personalized real-time dosimetry in computed tomography, and the company Fibermetrix has developed a new device named IVISCAN
® based on this technology. In this study, we evaluated performances of IVISCAN® and associated uncertainties in terms of dose-rate dependence, angular dependence, stability with cumulative dose, repeatability, energy dependence, length dependence, and special uniformity in reference and clinical computed tomography beam qualities. For repeatability, the standard deviation is less than 0.039%, and the absolute uncertainty of repeatability lies between 0.017% and 0.025%. The deviation between IVISCAN® and the reference regarding energy dependence is less than 1.88% in clinical use. Dose rate dependence results show a maximum deviation under ±2%. Angular dependence standard deviation σ is 0.8%, and the absolute uncertainty was 1.6%. We observed 1% of variation every 50 Gy steps up to a cumulative dose of 500 Gy. Probe response was found to be independent of the PSF length with a maximum deviation ΔDsize < 2.7% between the IVISCAN® probe and the 1 cm PSF probe. The presented results demonstrated that IVISCAN® performances are in accordance with metrology references and the international standard IEC61674 relative to dosemeters used in X-ray diagnostic imaging and then make it an ideal candidate for real-time dosimetry in CT applications.- Published
- 2021
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26. DNA Double-Strand Breaks Induced in Human Cells by Twelve Metallic Species: Quantitative Inter-Comparisons and Influence of the ATM Protein.
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Viau M, Sonzogni L, Ferlazzo ML, Berthel E, Pereira S, Bodgi L, Granzotto A, Devic C, Fervers B, Charlet L, and Foray N
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- Aluminum pharmacology, Ataxia Telangiectasia Mutated Proteins drug effects, Ataxia Telangiectasia Mutated Proteins radiation effects, Cadmium pharmacology, Chromium pharmacology, Copper pharmacology, DNA Repair radiation effects, Humans, Iron pharmacology, Lead pharmacology, Metals pharmacology, Metals toxicity, Nickel pharmacology, Palladium pharmacology, Zinc pharmacology, Ataxia Telangiectasia Mutated Proteins chemistry, DNA Breaks, Double-Stranded drug effects, DNA Repair drug effects, Metals chemistry
- Abstract
Despite a considerable amount of data, the molecular and cellular bases of the toxicity due to metal exposure remain unknown. Recent mechanistic models from radiobiology have emerged, pointing out that the radiation-induced nucleo-shuttling of the ATM protein (RIANS) initiates the recognition and the repair of DNA double-strand breaks (DSB) and the final response to genotoxic stress. In order to document the role of ATM-dependent DSB repair and signalling after metal exposure, we applied twelve different metal species representing nine elements (Al, Cu, Zn Ni, Pd, Cd, Pb, Cr, and Fe) to human skin, mammary, and brain cells. Our findings suggest that metals may directly or indirectly induce DSB at a rate that depends on the metal properties and concentration, and tissue type. At specific metal concentration ranges, the nucleo-shuttling of ATM can be delayed which impairs DSB recognition and repair and contributes to toxicity and carcinogenicity. Interestingly, as observed after low doses of ionizing radiation, some phenomena equivalent to the biological response observed at high metal concentrations may occur at lower concentrations. A general mechanistic model of the biological response to metal exposure based on the nucleo-shuttling of ATM is proposed to describe the metal-induced stress response and to define quantitative endpoints for toxicity and carcinogenicity.
- Published
- 2021
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27. Fibroblasts from Retinoblastoma Patients Show Radiosensitivity Linked to Abnormal Localization of the ATM Protein.
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Moulay Lakhdar I, Ferlazzo ML, Al Choboq J, Berthel E, Sonzogni L, Devic C, Granzotto A, Thariat J, and Foray N
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- Anticholesteremic Agents therapeutic use, Bone Density Conservation Agents therapeutic use, Cell Line, DNA Breaks, Double-Stranded, DNA Repair, Drug Combinations, Fibroblasts drug effects, Fibroblasts metabolism, Humans, Pravastatin therapeutic use, Radiation Dosage, Retinoblastoma Binding Proteins metabolism, Skin drug effects, Skin metabolism, Ubiquitin-Protein Ligases metabolism, X-Rays, Zoledronic Acid therapeutic use, Ataxia Telangiectasia Mutated Proteins metabolism, Fibroblasts radiation effects, Radiation Tolerance physiology, Retinal Neoplasms pathology, Retinoblastoma pathology, Skin radiation effects
- Abstract
Purpose/aim of the Study: Retinoblastoma (Rb) is a rare form of pediatric cancer that develops from retina cells. Bilateral and some unilateral forms of Rb are associated with heterozygous germline mutations of the (retinoblastoma 1) RB1 gene. RB1 mutations are also associated with a significant risk of secondary malignancy like head and neck tumors. Hence, to date, even if Rb patients are less subjected to radiotherapy to treat their primary ocular tumors, their healthy tissues may be exposed to significant doses of ionizing radiation during the treatment against their secondary malignancies with a significant risk of adverse tissue reactions (radiosensitivity) and/or radiation-induced cancer (radiosusceptibility). However, the biological role of the Rb protein in response to radiation remains misunderstood. Since the ataxia telangiectasia mutated (ATM) protein is a key protein of radiation response and since untransformed skin fibroblasts are a current model to quantify cellular radiosensitivity, we investigated here for the first time the functionality of the ATM-dependent signaling and repair pathway of the radiation-induced DNA double-strand breaks (DSB) in irradiated skin fibroblasts derived from Rb patients., Materials and Methods: The major biomarkers of the DSB repair and signaling, namely clonogenic cell survival, micronuclei, nuclear foci of the phosphorylated forms of the X variant of the H2A histone (γH2AX), the phosphorylated forms of the ATM protein (pATM) and the meiotic recombination 11 nuclease (MRE11) were assessed in untransformed skin fibroblasts derived from three Rb patients., Results: Skin fibroblasts from Rb patients showed significant cellular radiosensitivity, incomplete DSB recognition, delay in the ATM nucleo-shuttling and exacerbated MRE11 nuclease activity. Treatment with statin and bisphosphonates led to significant complementation of these impairments., Conclusions: Our findings strongly suggest the involvement of the ATM kinase in the radiosensitivity/radiosusceptibility phenotype observed in Rb cases.
- Published
- 2021
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28. First radiobiological characterization of the McCune-Albright syndrome: influence of the ATM protein and effect of statins + bisphosphonates treatment.
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Bachelet JT, Granzotto A, Ferlazzo M, Sonzogni L, Berthel E, Devic C, and Foray N
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- Adult, Cell Line, DNA Repair, Female, Fibroblasts radiation effects, Fibrous Dysplasia, Polyostotic genetics, Humans, MRE11 Homologue Protein analysis, Male, Osteoblasts radiation effects, Ataxia Telangiectasia Mutated Proteins physiology, Diphosphonates administration & dosage, Fibrous Dysplasia, Polyostotic drug therapy, Hydroxymethylglutaryl-CoA Reductase Inhibitors administration & dosage, Radiation Tolerance
- Abstract
Purpose: MacCune-Albright syndrome (MAS) is a rare autosomal dominant osteo-hormonal disorder. MAS is characterized by a severe form of polyostotic fibrous dysplasia, 'café-au-lait' pigmentation of the skin and multiple endocrinopathies. MAS was shown to be caused by mosaic missense somatic mutations in the GNAS gene coding for the alpha-subunit of the stimulatory G-protein. MAS is also associated with radiation-induced malignant tumors, like osteosarcoma, fibrosarcoma and chondrosarcoma but their origin remains misunderstood. In parallel, bisphosphonates treatment was shown to improve the MAS patients' outcome, notably by increasing bone density but, again, the molecular mechanisms supporting these observations remain misunderstood., Materials and Methods: Here, by using fibroblast and osteoblast cell lines derived from 2 MAS patients, the major radiobiological features of MAS were investigated. Notably, the clonogenic cell survival, the micronuclei and the γH2AX, pATM and MRE11 immunofluorescence assays were applied to MAS cells., Results: It appears that cells from the 2 MAS patients are associated with a moderate but significant radiosensitivity, a delayed radiation-induced nucleoshuttling of the ATM kinase likely caused by its sequestration in cytoplasm, suggesting impaired DNA double-strand breaks (DSB) repair and signaling in both fibroblasts and osteoblasts. Such delay may be partially corrected by using bisphosphonates combined with statins, which renders cells more radioresistant., Conclusions: Our findings represent the first radiobiological characterization of fibroblasts and osteoblasts providing from MAS patients. Although the number of studied cases is reduced, our findings suggest that the MAS cells tested belong to the group of syndromes associated with moderate but significant radiosensitivity. Further investigations are however required to secure the clinical transfer of the combination of bisphosphonates and statins, to reduce the disease progression and to better evaluate the potential risks linked to radiation exposure.
- Published
- 2021
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29. Influence of Individual Radiosensitivity on the Hormesis Phenomenon: Toward a Mechanistic Explanation Based on the Nucleoshuttling of ATM Protein.
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Devic C, Ferlazzo ML, Berthel E, and Foray N
- Abstract
Hormesis is a low-dose phenomenon that has been reported to occur, to different extents, in animals, plants, and microorganisms. However, a review of the literature shows that only a few reports describe it in humans. Also, the diversity of experimental protocols and cellular models used makes deciphering the mechanisms of hormesis difficult. In humans, hormesis mostly appears in the 20 to 75 mGy dose range and in nontransformed, radioresistant cells. In a previous paper by Devic et al, a biological interpretation of the adaptive response (AR) phenomenon was proposed using our model that is based on the radiation-induced nucleoshuttling of the ATM protein (the RIANS model). Here, we showed that the 20 to 75 mGy dose range corresponds to a maximum amount of ATM monomers diffusing into the nucleus, while no DNA double-strand breaks is produced by radiation. These ATM monomers are suggested to help in recognizing and repairing spontaneous DNA breaks accumulated in cells and contribute to reductions in genomic instability and aging. The RIANS model also permitted the biological interpretation of hypersensitivity to low doses (HRS)-another low-dose phenomenon. Hence, for the first time to our knowledge, hormesis, AR, and HRS can be explained using the same unified molecular model., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2020.)
- Published
- 2020
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30. Some mutations in the xeroderma pigmentosum D gene may lead to moderate but significant radiosensitivity associated with a delayed radiation-induced ATM nuclear localization.
- Author
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Ferlazzo M, Berthel E, Granzotto A, Devic C, Sonzogni L, Bachelet JT, Pereira S, Bourguignon M, Sarasin A, Mezzina M, and Foray N
- Subjects
- Cell Line, Cell Survival, Chromatin metabolism, DNA Breaks, Double-Stranded, Fibroblasts drug effects, Fibroblasts metabolism, Humans, MRE11 Homologue Protein metabolism, Micronucleus Tests, Radiation Tolerance, Radiation, Ionizing, Ultraviolet Rays, X-Rays, Active Transport, Cell Nucleus, Ataxia Telangiectasia Mutated Proteins metabolism, Mutation, Xeroderma Pigmentosum genetics, Xeroderma Pigmentosum Group D Protein genetics
- Abstract
Purpose: Xeroderma Pigmentosum (XP) is a rare, recessive genetic disease associated with photosensitivity, skin cancer proneness, neurological abnormalities and impaired nucleotide excision repair of the UV-induced DNA damage. Less frequently, XP can be associated with sensitivity to ionizing radiation (IR). Here, a complete radiobiological characterization was performed on a panel of fibroblasts derived from XP-group D patients (XPD). Materials and methods: Cellular radiosensitivity and the functionality of the recognition and repair of chromosome breaks and DNA double-strand breaks (DSB) was evaluated by different techniques including clonogenic cell survival, micronuclei, premature chromosome condensation, pulsed-field gel electrophoresis, chromatin decondensation and immunofluorescence assays. Quantitative correlations between each endpoint were analyzed systematically. Results: Among the seven fibroblast cell lines tested, those derived from three non-relative patients holding the p.[Arg683Trp];[Arg616Pro] XPD mutations showed significant cellular radiosensitivity, high yield of residual micronuclei, incomplete DSB recognition, DSB and chromosome repair defects, impaired ATM, MRE11 relocalization, significant chromatin decondensation. Interestingly, XPD transduction and treatment with statins and bisphosphonates known to accelerate the radiation-induced ATM nucleoshuttling led to significant complementation of these impairments. Conclusions: Our findings suggest that some subsets of XPD patients may be at risk of radiosensitivity reactions and treatment with statins and bisphosphonates may be an interesting approach of radioprotection countermeasure. Different mechanistic models were discussed to better understand the potential specificity of the p.[Arg683Trp];[Arg616Pro] XPD mutations.
- Published
- 2020
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31. What Does the History of Research on the Repair of DNA Double-Strand Breaks Tell Us?-A Comprehensive Review of Human Radiosensitivity.
- Author
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Berthel E, Ferlazzo ML, Devic C, Bourguignon M, and Foray N
- Subjects
- Animals, Ataxia Telangiectasia Mutated Proteins genetics, Ataxia Telangiectasia Mutated Proteins metabolism, Biomarkers metabolism, Cytogenetics history, DNA End-Joining Repair, Histones metabolism, History, 20th Century, History, 21st Century, Humans, Radiation, Ionizing, Research history, DNA Breaks, Double-Stranded, DNA Repair genetics, Radiation Tolerance genetics
- Abstract
Our understanding of the molecular and cellular response to ionizing radiation (IR) has progressed considerably. This is notably the case for the repair and signaling of DNA double-strand breaks (DSB) that, if unrepaired, can result in cell lethality, or if misrepaired, can cause cancer. However, through the different protocols, techniques, and cellular models used during the last four decades, the DSB repair kinetics and the relationship between cellular radiosensitivity and unrepaired DSB has varied drastically, moving from all-or-none phenomena to very complex mechanistic models. To date, personalized medicine has required a reliable evaluation of the IR-induced risks that have become a medical, scientific, and societal issue. However, the molecular bases of the individual response to IR are still unclear: there is a gap between the moderate radiosensitivity frequently observed in clinic but poorly investigated in the publications and the hyper-radiosensitivity of rare but well-characterized genetic diseases frequently cited in the mechanistic models. This paper makes a comprehensive review of semantic issues, correlations between cellular radiosensitivity and unrepaired DSB, shapes of DSB repair curves, and DSB repair biomarkers in order to propose a new vision of the individual response to IR that would be more coherent with clinical reality.
- Published
- 2019
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32. Influence of Linear Energy Transfer on the Nucleo-shuttling of the ATM Protein: A Novel Biological Interpretation Relevant for Particles and Radiation.
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Maalouf M, Granzotto A, Devic C, Bodgi L, Ferlazzo M, Peaucelle C, Bajard M, Giraud JY, Balosso J, Hérault J, Biston MC, Malet C, and Foray N
- Subjects
- Ataxia Telangiectasia Mutated Proteins genetics, Carbon chemistry, Cell Line, Cell Line, Tumor, Cell Nucleus metabolism, Cell Survival, DNA Damage, Fibroblasts radiation effects, Gamma Rays, Histones metabolism, Humans, Ions, Kinetics, Microscopy, Fluorescence, Permeability, Protons, Radiometry, Ataxia Telangiectasia Mutated Proteins metabolism, DNA Breaks, Double-Stranded, DNA Repair, Linear Energy Transfer, Radiation Tolerance
- Abstract
Purpose: Linear energy transfer (LET) plays an important role in radiation response. Recently, the radiation-induced nucleo-shuttling of ATM from cytoplasm to the nucleus was shown to be a major event of the radiation response that permits a normal DNA double-strand break (DSB) recognition and repair. Here, we aimed to verify the relevance of the ATM nucleo-shuttling model for high-LET particles and various radiation types., Methods and Materials: ATM- and H2AX-immunofluorescence was used to assess the number of recognized and unrepaired DSB in quiescent fibroblast cell lines exposed to x-rays, γ-rays, 9- and 12-MeV electrons, 3- and 65-MeV protons and 75-MeV/u carbon ions., Results: The rate of radiation-induced ATM nucleo-shuttling was found to be specific to each radiation type tested. By increasing the permeability of the nuclear membrane with statin and bisphosphonates, 2 fibroblast cell lines exposed to high-LET particles were shown to be protected by an accelerated ATM nucleo-shuttling., Conclusions: Our findings are in agreement with the conclusion that LET and the radiation/particle type influence the formation of ATM monomers in cytoplasm that are required for DSB recognition. A striking analogy was established between the DSB repair kinetics of radioresistant cells exposed to high-LET particles and that of several radiosensitive cells exposed to low-LET radiation. Our data show that the nucleo-shuttling of ATM provides crucial elements to predict radiation response in human quiescent cells, whatever the LET value and their radiosensitivity., (Copyright © 2018 Elsevier Inc. All rights reserved.)
- Published
- 2019
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33. DNA breaks induced by iodine-containing contrast medium in radiodiagnostics: a problem of tungsten?
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Ferlazzo ML, Devic C, Granzotto A, Charvet AM, Pilleul F, Colin C, Biston MC, Joubert A, Bourguignon M, and Foray N
- Abstract
Iodine-containing contrast media (ICM) are extensively used to improve image quality and information content in x-ray-based examinations, particularly in computed tomography (CT). In parallel, there is increasing evidence that the use of ICM during CT sessions is associated with deoxyribonucleic acid (DNA) breaks that may influence the estimation of the risks linked to x-ray exposure. Why has iodine been preferred to any other heavy elements to enhance contrast in radiodiagnostics? How to understand such DNA breaks effect? We searched for the answers in the early times of x-ray medical use. It appeared that the maximal ratio between the relative iodine and water mass energy absorption coefficients is reached in the range of 40-60 keV, which defines the energy range in which the dose is preferentially absorbed by ICM. This range does not correspond to the K-edge of iodine but to that of tungsten, the major component of the x-ray tube anode of CT scanners. At such energy, radiolysis of the ICM produces sodium or potassium iodide that prevents a normal DNA breaks repair and influences the individual response to x-ray low-dose. Both contrast enhancement and DNA breaks effect may therefore be caused by tungsten of the anodes of x-ray tubes., Competing Interests: Not applicableNot applicableThe PhD thesis of CD was supported by Fibermetrix (Strasbourg, France) and Neolys Diagnostics (Lyon, France). The remaining authors declare no competing interests.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
- Published
- 2018
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34. Influence of Individual Radiosensitivity on the Adaptive Response Phenomenon: Toward a Mechanistic Explanation Based on the Nucleo-Shuttling of ATM Protein.
- Author
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Devic C, Ferlazzo ML, and Foray N
- Abstract
The adaptive response (AR) phenomenon generally describes a protective effect caused by a "priming" low dose ( d
AR ) delivered after a period of time (Δ tAR ) before a higher "challenging" dose ( DAR ). The AR is currently observed in human cells if dAR , Δ tAR , and DAR belong to (0.001-0.5 Gy), (2-24 hours), (0.1-5 Gy), respectively. In order to investigate the molecular mechanisms specific to AR in human cells, we have systematically reviewed the experimental AR protocols, the cellular models, and the biological endpoints used from the 1980s. The AR appears to be preferentially observed in radiosensitive cells and is strongly dependent on individual radiosensitivity. To date, the model of the nucleo-shuttling of the ATM protein provides a relevant mechanistic explanation of the AR molecular and cellular events. Indeed, the priming dose dAR may result in the diffusion of a significant amount of active ATM monomers in the nucleus. These ATM monomers, added to those induced directly by the challenging dose DAR , may increase the efficiency of the response to DAR by a better ATM-dependent DNA damage recognition. Such mechanistic model would also explain why AR is not observed in radioresistant or hyperradiosensitive cells. Further investigations at low dose are needed to consolidate our hypotheses., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.- Published
- 2018
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35. Radiobiological Characterization of Tuberous Sclerosis: a Delay in the Nucleo-Shuttling of ATM May Be Responsible for Radiosensitivity.
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Ferlazzo ML, Bach-Tobdji MKE, Djerad A, Sonzogni L, Devic C, Granzotto A, Bodgi L, Bachelet JT, Djefal-Kerrar A, Hennequin C, and Foray N
- Subjects
- Cell Line, Cell Nucleus radiation effects, Cell Survival radiation effects, DNA Breaks, Double-Stranded, Fibroblasts metabolism, Fibroblasts radiation effects, Humans, Protein Transport, Radiation Tolerance, Tuberous Sclerosis Complex 1 Protein metabolism, Tuberous Sclerosis Complex 2 Protein metabolism, Ataxia Telangiectasia Mutated Proteins metabolism, Cell Nucleus metabolism, Cell Survival physiology, Tuberous Sclerosis metabolism
- Abstract
The tuberous sclerosis complex (TSC) syndrome is associated with numerous cutaneous pathologies (notably on the face), epilepsy, intellectual disability and developmental retardation and, overall, high occurrence of benign tumors in several organs, like angiofibromas, giant cell astrocytomas, renal angiomyolipomas, and pulmonary lymphangioleiomyomatosis. TSC is caused by mutations of either of the hamartin or tuberin proteins that are mainly cytoplasmic. Some studies published in the 1980s reported that TSC is associated with radiosensitivity. However, its molecular basis in TSC cells is not documented enough. Here, we examined the functionality of the repair and signaling of radiation-induced DNA double-strand breaks (DSB) in fibroblasts derived from TSC patients. Quiescent TSC fibroblast cells elicited abnormally low rate of recognized DSB reflected by a low yield of nuclear foci formed by phosphorylated H2AX histones. Irradiated TSC cells also presented a delay in the nucleo-shuttling of the ATM kinase, potentially due to a specific binding of ATM to mutated TSC protein in cytoplasm. Lastly, TSC fibroblasts showed abnormally high MRE11 nuclease activity suggesting genomic instability. A combination of biphosphonates and statins complemented these impairments by facilitating the nucleoshuttling of ATM and increasing the yield of recognized DSB. Our results showed that TSC belongs to the group of syndromes associated with low but significant defect of DSB signaling and delay in the ATM nucleo-shuttling associated with radiosensitivity.
- Published
- 2018
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36. In Reply to Azria et al.
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Pereira S, Bodgi L, Duclos M, Canet A, Ferlazzo ML, Devic C, Granzotto A, Deneuve S, Vogin G, and Foray N
- Published
- 2018
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37. Fast and Binary Assay for Predicting Radiosensitivity Based on the Theory of ATM Nucleo-Shuttling: Development, Validation, and Performance.
- Author
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Pereira S, Bodgi L, Duclos M, Canet A, Ferlazzo ML, Devic C, Granzotto A, Deneuve S, Vogin G, and Foray N
- Subjects
- Cell Line, Enzyme-Linked Immunosorbent Assay, Fibroblasts radiation effects, Humans, Phosphorylation, Ataxia Telangiectasia Mutated Proteins metabolism, Radiation Tolerance
- Abstract
Purpose: To examine the possibility of predicting clinical radiosensitivity by quantifying the nuclear forms of autophosphorylated ATM protein (pATM) via a specific enzyme-linked immunosorbent assay (ELISA)., Methods and Materials: This study was performed on 30 skin fibroblasts from 9 radioresistant patients and 21 patients with adverse tissue reaction events. Patients were divided into 2 groups: radioresistant (toxicity grade <2) and radiosensitive (toxicity grade ≥2). The quantity of nuclear pATM molecules was assessed by the ELISA method at 10 minutes and 1 hour after 2 Gy and compared with pATM immunofluorescence data., Results: The pATM ELISA data were in quantitative agreement with the immunofluorescence data. A receiver operating characteristic analysis was applied first to 2 data sets (a training set [n=14] and a validating [n=16] set) and thereafter to all the data with a 2-fold cross-validation method. The assay showed an area under the curve value higher than 0.8, a sensitivity of 0.8, and a specificity ranging from 0.75 to 1, which strongly documents the predictive power of the pATM ELISA., Conclusion: This study showed that the assessment of nuclear pATM quantity after 2 Gy via an ELISA technique can be the basis of a predictive assay with the highest statistical performance among the available predictive approaches., (Copyright © 2017 Elsevier Inc. All rights reserved.)
- Published
- 2018
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38. [Repeated radiation dose effect and DNA repair: Importance of the individual factor and the time interval between the doses].
- Author
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Viau M, Perez AF, Bodgi L, Devic C, Granzotto A, Ferlazzo ML, Bourguignon M, Puisieux A, Lacornerie T, Lartigau É, Lagrange JL, and Foray N
- Subjects
- Radiation Dosage, Time Factors, DNA Repair radiation effects, Dose Fractionation, Radiation
- Abstract
The dose fractionation effect is a recurrent question of radiation biology research that remains unsolved since no model predicts the clinical effect only with the cumulated dose and the radiobiology of irradiated tissues. Such an important question is differentially answered in radioprotection, radiotherapy, radiology or epidemiology. A better understanding of the molecular response to radiation makes possible today a novel approach to identify the parameters that condition the fractionation effect. Particularly, the time between doses appears to be a key factor since it will permit, or not, the repair of certain radiation-induced DNA damages whose repair rates are of the order of seconds, minutes or hours: the fractionation effect will therefore vary according to the functionality of the different repair pathways, whatever for tumor or normal tissues., (Copyright © 2016 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.)
- Published
- 2016
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39. Influence of Nucleoshuttling of the ATM Protein in the Healthy Tissues Response to Radiation Therapy: Toward a Molecular Classification of Human Radiosensitivity.
- Author
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Granzotto A, Benadjaoud MA, Vogin G, Devic C, Ferlazzo ML, Bodgi L, Pereira S, Sonzogni L, Forcheron F, Viau M, Etaix A, Malek K, Mengue-Bindjeme L, Escoffier C, Rouvet I, Zabot MT, Joubert A, Vincent A, Dalla Venezia N, Bourguignon M, Canat EP, d'Hombres A, Thébaud E, Orbach D, Stoppa-Lyonnet D, Radji A, Doré E, Pointreau Y, Bourgier C, Leblond P, Defachelles AS, Lervat C, Guey S, Feuvret L, Gilsoul F, Berger C, Moncharmont C, de Laroche G, Moreau-Claeys MV, Chavaudra N, Combemale P, Biston MC, Malet C, Martel-Lafay I, Laude C, Hau-Desbat NH, Ziouéche A, Tanguy R, Sunyach MP, Racadot S, Pommier P, Claude L, Baleydier F, Fleury B, de Crevoisier R, Simon JM, Verrelle P, Peiffert D, Belkacemi Y, Bourhis J, Lartigau E, Carrie C, De Vathaire F, Eschwege F, Puisieux A, Lagrange JL, Balosso J, and Foray N
- Subjects
- Analysis of Variance, Ataxia Telangiectasia Mutated Proteins genetics, Biopsy, Cell Line, DNA Repair, Fibroblasts radiation effects, Humans, Micronucleus Tests methods, Phosphorylation, Radiation Injuries metabolism, Radiation Injuries pathology, Radiation Tolerance genetics, Skin pathology, Time Factors, Ataxia Telangiectasia Mutated Proteins metabolism, Cell Nucleus metabolism, DNA Breaks, Double-Stranded, Histones metabolism, Radiation Injuries classification, Radiation Tolerance physiology, Skin radiation effects
- Abstract
Purpose: Whereas post-radiation therapy overreactions (OR) represent a clinical and societal issue, there is still no consensual radiobiological endpoint to predict clinical radiosensitivity. Since 2003, skin biopsy specimens have been collected from patients treated by radiation therapy against different tumor localizations and showing a wide range of OR. Here, we aimed to establish quantitative links between radiobiological factors and OR severity grades that would be relevant to radioresistant and genetic hyperradiosensitive cases., Methods and Materials: Immunofluorescence experiments were performed on a collection of skin fibroblasts from 12 radioresistant, 5 hyperradiosensitive, and 100 OR patients irradiated at 2 Gy. The numbers of micronuclei, γH2AX, and pATM foci that reflect different steps of DNA double-strand breaks (DSB) recognition and repair were assessed from 10 minutes to 24 hours after irradiation and plotted against the severity grades established by the Common Terminology Criteria for Adverse Events and the Radiation Therapy Oncology Group., Results: OR patients did not necessarily show a gross DSB repair defect but a systematic delay in the nucleoshuttling of the ATM protein required for complete DSB recognition. Among the radiobiological factors, the maximal number of pATM foci provided the best discrimination among OR patients and a significant correlation with each OR severity grade, independently of tumor localization and of the early or late nature of reactions., Conclusions: Our results are consistent with a general classification of human radiosensitivity based on 3 groups: radioresistance (group I); moderate radiosensitivity caused by delay of nucleoshuttling of ATM, which includes OR patients (group II); and hyperradiosensitivity caused by a gross DSB repair defect, which includes fatal cases (group III)., (Copyright © 2016 Elsevier Inc. All rights reserved.)
- Published
- 2016
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40. [Management of craniofacial type 1 neurofibromatosis].
- Author
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Bachelet JT, Combemale P, Devic C, Foray N, Jouanneau E, and Breton P
- Subjects
- Facial Neoplasms diagnosis, Facial Neoplasms therapy, Head and Neck Neoplasms diagnosis, Humans, Neurofibroma, Plexiform diagnosis, Neurofibroma, Plexiform therapy, Neurofibromatosis 1 diagnosis, Orbital Neoplasms pathology, Orbital Neoplasms therapy, Plastic Surgery Procedures methods, Skull Neoplasms diagnosis, Skull Neoplasms therapy, Head and Neck Neoplasms therapy, Neurofibromatosis 1 therapy
- Abstract
Type I neurofibromatosis (NF) is the most common autosomal dominant disease. It concerns one in 3000 births, the penetrance is close to 100% and 50% of new cases are de novo mutations (17q11.2 chromosome 17 location). Cranio-maxillofacial region is concerned in 10% of the cases, in different forms: molluscum neurofibroma, plexiform neurofibroma, cranio-orbital neurofibroma, parotido-jugal neurofibroma, cervical neurofibroma. These lesions have different prognosis depending on the craniofacial localization: ocular functional risk, upper airway compressive risk, nerve compression risk, aesthetic and social impact. The maxillofacial surgeon in charge of patients with type I NF should follow the patient from the diagnosis and organize the different surgical times in order to take care about the different issues: vital, functional and aesthetic. We describe the treatment of facial localizations of type 1 NF as it is done at the University Hospital of Lyon and at the Rhône-Alpes-Auvergne neurofibromatosis reference center., (Copyright © 2015 Elsevier Masson SAS. All rights reserved.)
- Published
- 2015
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41. [The low doses of radiation: Towards a new reading of the risk assessment].
- Author
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Perez AF, Devic C, Colin C, and Foray N
- Subjects
- Adaptation, Physiological, Astronauts, Dose-Response Relationship, Radiation, Environmental Exposure, Health Personnel, Hormesis physiology, Humans, Models, Animal, Occupational Diseases etiology, Occupational Exposure adverse effects, Radioactive Fallout adverse effects, Radioactive Hazard Release, Radioactivity, Radiotherapy Dosage, Risk Assessment, Neoplasms, Radiation-Induced etiology, Radiation Dosage, Radiation Tolerance
- Abstract
From Hiroshima bomb explosion data, the risk of radiation-induced cancer is significant from 100 mSv for a population considered as uniform and radioresistant. However, the recent radiobiological data bring some new elements that highlight some features that were not taken into account: the individual factor, the dose rate and the repeated dose effect. The objective evaluation of the cancer risk due to doses lower than 100 mSv is conditioned by high levels of measurability and statistical significance. However, it appears that methodological rigor is not systematically applied in all the papers. Furthermore, unclear communication in press often leads to some announcement effects, which does not improve the readability of the issue. This papers aims to better understand the complexity of the low-dose-specific phenomena as a whole, by confronting the recent biological data with epidemiological data., (Copyright © 2015 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)
- Published
- 2015
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42. Mutations of the Huntington's disease protein impact on the ATM-dependent signaling and repair pathways of the radiation-induced DNA double-strand breaks: corrective effect of statins and bisphosphonates.
- Author
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Ferlazzo ML, Sonzogni L, Granzotto A, Bodgi L, Lartin O, Devic C, Vogin G, Pereira S, and Foray N
- Subjects
- Ataxia Telangiectasia Mutated Proteins metabolism, Cells, Cultured, DNA Breaks, Double-Stranded drug effects, DNA Repair drug effects, DNA Repair genetics, Female, Fibroblasts drug effects, Fibroblasts physiology, Humans, Huntingtin Protein, Huntington Disease metabolism, Male, Mutation drug effects, Mutation genetics, Ataxia Telangiectasia Mutated Proteins genetics, DNA Breaks, Double-Stranded radiation effects, Diphosphonates pharmacology, Huntington Disease genetics, Hydroxymethylglutaryl-CoA Reductase Inhibitors pharmacology, Nerve Tissue Proteins genetics
- Abstract
Huntington's disease (HD) is a neurodegenerative syndrome caused by mutations of the IT15 gene encoding for the huntingtin protein. Some research groups have previously shown that HD is associated with cellular radiosensitivity in quiescent cells. However, there is still no mechanistic model explaining such specific clinical feature. Here, we examined the ATM-dependent signaling and repair pathways of the DNA double-strand breaks (DSB), the key damage induced by ionizing radiation, in human HD skin fibroblasts. Early after irradiation, quiescent HD fibroblasts showed an abnormally low rate of recognized DSB managed by non-homologous end-joining reflected by a low yield of nuclear foci formed by phosphorylated H2AX histones and by 53BP1 protein. Furthermore, HD cells elicited a significant but moderate yield of unrepaired DSB 24 h after irradiation. Irradiated HD cells also presented a delayed nucleo-shuttling of phosphorylated forms of the ATM kinase, potentially due to a specific binding of ATM to mutated huntingtin in the cytoplasm. Our results suggest that HD belongs to the group of syndromes associated with a low but significant defect of DSB signaling and repair defect associated with radiosensitivity. A combination of biphosphonates and statins complements these impairments by facilitating the nucleo-shuttling of ATM, increasing the yield of recognized and repaired DSB.
- Published
- 2014
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43. Impact of dose-rate on the low-dose hyper-radiosensitivity and induced radioresistance (HRS/IRR) response.
- Author
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Thomas C, Martin J, Devic C, Bräuer-Krisch E, Diserbo M, Thariat J, and Foray N
- Subjects
- Animals, Cell Line, Tumor, Cobalt Radioisotopes, Colon metabolism, Colon pathology, Colon radiation effects, DNA Breaks, Double-Stranded radiation effects, DNA Repair radiation effects, Gamma Rays therapeutic use, Humans, Rats, X-Rays, Radiation Dosage, Radiation Tolerance radiation effects
- Abstract
Purpose: To ask whether dose-rate influences low-dose hyper- radiosensitivity and induced radioresistance (HRS/IRR) response in rat colon progressive (PRO) and regressive (REG) cells., Methods: Clonogenic survival was applied to tumorigenic PRO and non-tumorigenic REG cells irradiated with (60)Co γ-rays at 0.0025-500 mGy.min(-1). Both clonogenic survival and non-homologous end-joining (NHEJ) pathway involved in DNA double-strand breaks (DSB) repair assays were applied to PRO cells irradiated at 25 mGy.min(-1) with 75 kV X-rays only., Results: Irrespective of dose-rates, marked HRS/IRR responses were observed in PRO but not in REG cells. For PRO cells, the doses at which HRS and IRR responses are maximal were dependent on dose-rate; conversely exposure times during which HRS and IRR responses are maximal (t(HRSmax) and t(IRRmax)) were independent of dose-rate. The t(HRSmax) and t(IRRmax) values were 23 ± 5 s and 66 ± 7 s (mean ± standard error of the mean [SEM], n = 7), in agreement with literature data. Repair data show that t(HRSmax) may correspond to exposure time during which NHEJ is deficient while t(IRRmax) may correspond to exposure time during which NHEJ is complete., Conclusion: HRS response may be maximal if exposure times are shorter than t(HRSmax) irrespective of dose, dose-rate and cellular model. Potential application of HRS response in radiotherapy is discussed.
- Published
- 2013
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44. A single formula to describe radiation-induced protein relocalization: towards a mathematical definition of individual radiosensitivity.
- Author
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Bodgi L, Granzotto A, Devic C, Vogin G, Lesne A, Bottollier-Depois JF, Victor JM, Maalouf M, Fares G, and Foray N
- Subjects
- Antibodies, Antinuclear chemistry, Fibroblasts pathology, Humans, Kinetics, Protein Transport radiation effects, Radiotherapy adverse effects, X-Rays adverse effects, DNA Damage, DNA Repair, Fibroblasts metabolism, Gamma Rays adverse effects, Models, Biological, Radiation Tolerance radiation effects
- Abstract
Immunofluorescence with antibodies against DNA damage repair and signaling protein is revolutionarising the estimation of the genotoxic risk. Indeed, a number of stress response proteins relocalize in nucleus as identifiable foci whose number, pattern and appearance/disappearance rate depend on several parameters such as the stress nature, dose, time and individual factor. Few authors proposed biomathematical tools to describe them in a unified formula that would be relevant for all the relocalizable proteins. Based on our two previous reports in this Journal (Foray et al., 2005; Gastaldo et al., 2008), we considered that foci response to stress is composed of a recognition and a repair phase, both described by an inverse power function provided from a Euler's Gamma distribution. The resulting unified formula called "Bodgi's function" is able to describe appearance/disappearance kinetics of nuclear foci after any condition of genotoxic stress. By applying the Bodgi's formula to DNA damage repair data from 45 patients treated with radiotherapy, we deduced a classification of human radiosensitivity based on objective molecular criteria, notably like the number of unrepaired DNA double-strand breaks and the radiation-induced nucleo-shuttling of the ATM kinase., (Copyright © 2013 Elsevier Ltd. All rights reserved.)
- Published
- 2013
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45. Updated relevance of mammographic screening modalities in women previously treated with chest irradiation for Hodgkin disease.
- Author
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Colin C, de Vathaire F, Noël A, Charlot M, Devic C, Foray N, and Valette PJ
- Subjects
- Adult, Age Factors, Breast Neoplasms diagnostic imaging, Breast Neoplasms epidemiology, DNA Damage, Female, Humans, Neoplasms, Second Primary diagnostic imaging, Neoplasms, Second Primary epidemiology, Radiation Dosage, Radiotherapy Dosage, Risk Factors, Breast Neoplasms prevention & control, Hodgkin Disease radiotherapy, Mammography, Neoplasms, Second Primary prevention & control
- Published
- 2012
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46. DNA double-strand breaks induced by mammographic screening procedures in human mammary epithelial cells.
- Author
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Colin C, Devic C, Noël A, Rabilloud M, Zabot MT, Pinet-Isaac S, Giraud S, Riche B, Valette PJ, Rodriguez-Lafrasse C, and Foray N
- Subjects
- Adult, Age Factors, Aged, Epithelial Cells radiation effects, Female, Histones analysis, Humans, Micronuclei, Chromosome-Defective, Middle Aged, Breast radiation effects, DNA Breaks, Double-Stranded, Mammography adverse effects
- Abstract
Purpose: To assess in vitro mammographic radiation-induced DNA damage in mammary epithelial cells from 30 patients with low (LR) or high (HR) family risk of breast cancer., Materials and Methods: Spontaneous and radiation-induced DNA double-strand breaks (DSB) were quantified by using immunofluorescence of the phosphorylated H2AX histone (γH2AX) in different conditions of mammography irradiation (2, 4, 2 + 2 mGy)., Results: HR patients showed significantly more spontaneous γH2AX foci than LR patients (p = 0.014). A significant dose-effect was observed, with an exacerbation in HR patients (p = 0.01). The dose repetition (2 + 2 mGy) provided more induced and more unrepaired DSB than 2 mGy and 4 mGy, and was exacerbated in HR (p = 0.006)., Conclusions: This study highlights the existence of DSB induced by mammography and revealed by γH2AX assay with two major radiobiological effects occurring: A low-dose effect, and a LOw and Repeated Dose (LORD) effect. All these effects were exacerbated in HR patients. These findings may lead us to re-evaluate the number of views performed in screening using a single view (oblique) in women whose mammographic benefit has not properly been proved such as HR patients.
- Published
- 2011
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47. [Radiation biology: major advances and perspectives for radiotherapy].
- Author
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Joubert A, Vogin G, Devic C, Granzotto A, Viau M, Maalouf M, Thomas C, Colin C, and Foray N
- Subjects
- DNA radiation effects, DNA Breaks, Double-Stranded, DNA Repair, Forecasting, Health Physics, Humans, Neoplasms radiotherapy, Neoplasms, Radiation-Induced etiology, Neoplastic Syndromes, Hereditary genetics, Polymorphism, Single Nucleotide, Radiation Oncology trends, Radiation Tolerance genetics, Radiation-Sensitizing Agents therapeutic use, Radiosurgery, Radiotherapy methods, Signal Transduction drug effects, Technology, Radiologic, Therapies, Investigational, Translational Research, Biomedical, Radiobiology trends, Radiotherapy trends
- Abstract
At the beginning of the 21st century, radiation biology is at a major turning point in its history. It must meet the expectations of the radiation oncologists, radiologists and the general public, but its purpose remains the same: to understand the molecular, cellular and tissue levels of lethal and carcinogenic effects of ionizing radiation in order to better protect healthy tissues and to develop treatments more effective against tumours. Four major aspects of radiobiology that marked this decade will be discussed: technological developments, the importance of signalling and repair of radiation-induced deoxyribonucleic acid (DNA) damage, the impact of individual factor in the response to radiation and the contribution of radiobiology to better choose innovative therapies such as protontherapy or stereotactic body radiation therapy (SBRT). A translational radiobiology should emerge with the help of radiotherapists and radiation physicists and by facilitating access to the new radio and/or chemotherapy modalities., (Copyright © 2011. Published by Elsevier SAS.)
- Published
- 2011
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48. Individual susceptibility to radiosensitivity and to genomic instability: its impact on low-dose phenomena.
- Author
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Granzotto A, Devic C, Viau M, Maalouf M, Joubert A, Massart C, Thomas C, and Foray N
- Subjects
- Animals, DNA Repair, Humans, Mammals, Models, Theoretical, Rodentia, Cells radiation effects, DNA Damage radiation effects, Dose-Response Relationship, Radiation, Genomic Instability radiation effects, Radiation, Ionizing
- Published
- 2011
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- View/download PDF
49. [Individual response to ionising radiation: What predictive assay(s) to choose?].
- Author
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Granzotto A, Joubert A, Viau M, Devic C, Maalouf M, Thomas C, Vogin G, Malek K, Colin C, Balosso J, and Foray N
- Subjects
- Animals, Cell Death radiation effects, Cell Hypoxia, Chromosomes, Human radiation effects, Clone Cells radiation effects, Colony-Forming Units Assay, DNA radiation effects, DNA Repair genetics, Dose-Response Relationship, Radiation, Genetic Association Studies, Genetic Predisposition to Disease, Humans, Mice, Neoplasms genetics, Neoplasms radiotherapy, Radiation Injuries genetics, Radiation Injuries prevention & control, Radiation Tolerance physiology, Radiometry, Radiotherapy adverse effects, Treatment Outcome, Genetic Variation, Radiation Tolerance genetics, Radiation, Ionizing
- Abstract
Individual response to ionizing radiation is an important information required to apply an efficient radiotherapy treatment against tumour and to avoid any adverse effects in normal tissues. In 1981, Fertil and Malaise have demonstrated that the post-irradiation local tumor control determined in vivo is correlated with clonogenic cell survival assessed in vitro. Furthermore, these authors have reminded the relevance of the concept of intrinsic radiosensitivity that is specific to each individual organ (Fertil and Malaise, 1981) [1]. To date, since clonogenicity assays are too time-consuming and do not provide any other molecular information, a plethora of research groups have attempted to determine the molecular bases of intrinsic radiosensitivity in order to propose reliable and faster predictive assays. To this aim, several approaches have been developed. Notably, the recent revolution in genomic and proteomic technologies is providing a considerable number of data but their link with radiosensitivity still remains to be elucidated. On another hand, the systematic screening of some candidate genes potentially involved in the radiation response is highlighting the complexity of the molecular and cellular mechanisms of DNA damage sensoring and signalling and shows that an abnormal radiation response is not necessarily due to the impairment of one single protein. Finally, more modest approaches consisting in focusing some specific functions of DNA repair seem to provide more reliable clues to predict over-acute reactions caused by radiotherapy. In this review, we endeavoured to analyse the contributions of these major approaches to predict human radiosensitivity., (Copyright © 2011 Académie des sciences. Published by Elsevier SAS. All rights reserved.)
- Published
- 2011
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50. Molecular and cellular response of the most extensively used rodent glioma models to radiation and/or cisplatin.
- Author
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Bencokova Z, Pauron L, Devic C, Joubert A, Gastaldo J, Massart C, Balosso J, and Foray N
- Subjects
- Animals, BRCA1 Protein genetics, BRCA1 Protein metabolism, Cell Line, Tumor, Cell Survival drug effects, Cell Survival radiation effects, DNA Breaks, Double-Stranded drug effects, DNA Breaks, Double-Stranded radiation effects, Disease Models, Animal, Dose-Response Relationship, Radiation, Flow Cytometry, Rats, Signal Transduction drug effects, Signal Transduction radiation effects, Antineoplastic Agents therapeutic use, Cisplatin therapeutic use, Glioma therapy, Radiotherapy methods
- Abstract
Purpose Anti-glioma strategies are generally based on trials involving rodent models whose choice remains based on proliferative capacity and availability. Recently, our group obtained the most protracted survival of rats bearing F98 gliomas by combining synchrotron X-rays and intracerebral cisplatin injection (Biston et al., Cancer Res, 64:2317-2323, 2004). The response to such treatment was suggested to be dependent on BRCA1, a tumour suppressor known to be involved in the response to radiation and cisplatin. In order to verify the impact of BRCA1 functionality upon success of anti-glioma trials, radiobiological features and BRCA1-dependent stress signalling were investigated in the most extensively used rodent glioma models. Methods Cell death pathways, cell cycle arrests, DNA repair and stress signalling were evaluated in response to radiation and cisplatin in C6, 9L and F98 models. Results Rodent glioma models showed a large spectrum of cellular radiation response. Surprisingly, BRCA1 was found to be functionally impaired in C6 and F98 favouring genomic instability, tumour heterogeneity and tolerance of unrepaired DNA damage. Significance Our findings strengthened the importance of the choice of the glioma model on genetic and radiobiological bases, inasmuch as all these rat glioma models are induced by nitrosourea-mediated mutagenesis that may favour specific gene mutations. Particularly, BRCA1 status may condition the response to anti-glioma treatments. Furthermore, since BRCA1 acts as a tumour suppressor in a number of malignancies, our findings raise also the question of the implication of BRCA1 in brain tumours formation.
- Published
- 2008
- Full Text
- View/download PDF
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