Philippe Voisin - Academia.edu (original) (raw)

Papers by Philippe Voisin

Radioprotection, 2006

De nombreuses études suggèrent que les cellules souches adultes et plus particulièrement les cell... more De nombreuses études suggèrent que les cellules souches adultes et plus particulièrement les cellules souches Mésenchymateuses humaines (CSMh) pourraient être utilisées pour réparer de nombreux organes. Nous avons étudié la capacité des CSMh à réduire les lésions cutanées radio induite. Pour induire des lésions sévères de la peau, des souris NOD/SCID ont été irradiées au niveau de la patte droite postérieure (30 Gy, débit 2,7 Gy/mn) en utilisant une source gamma au 60 Co. Les CSMh ont été injectées 24 heures après irradiation par voie intraveineuse. La présence de cellules humaines, la sévérité des lésions et les processus de cicatrisation ont été étudiés sur les échantillons de peau prélevés de 3 à 8 semaines après irradiation. Nous avons pu observer que chez les souris greffées avec des CSMh, le niveau d'atteinte cutanée radio induite est significativement plus faible. Les scores cliniques utilisés pour l'étude de l'évolution des lésions cutanées de la peau sont significativement améliorés et une cicatrisation plus rapide est observée en comparaison des souris non injectées. La présence de cellules humaines a pu être détectée par PCR quantitative dans les zones cutanées en cours de cicatrisation. Ces résultats suggèrent premièrement que les CSMh sont capables de coloniser la peau altérée par les rayonnements ionisants et deuxièmement qu'elles accélèrent le processus de réparation de ce tissu limitant ainsi les complications tissulaires radio induites. La greffe de CSMh pourrait être un traitement thérapeutique efficace des phases précoces du syndrome cutané radio induit ABSTRACT Mesenchymal stem cells favour healing of the cutaneous radiation syndrome.

Journal of Radiation Research, 2001

Because of the large number of cells to be analyzed in cases of overexposure to ionizing radiatio... more Because of the large number of cells to be analyzed in cases of overexposure to ionizing radiation, an automated imaging system is desirable for scoring both translocations and dicentrics. This system should include three essential steps: automatic metaphase finding, automatic image capture at high magnification, and, finally, optimized data analysis for aberration interpretation. We evaluated a new image analysis system (CYTOGEN, IMSTAR, France) and found that its metaphase finder saved time, as much as quadrupling the speed of scoring chromosomal aberrations. Automatic metaphase selection did not appear to induce bias. We confirmed the equivalence of observing aberrations on a screen after automatic image capture and direct observation under a microscope. This work validated all of the steps necessary for obtaining images for automatic chromosomal aberration detection. The protocols for the detection of translocations may now be applied for biological dosimetry. This step will be validated in a future study.

Radioprotection, 2010

En cas d'accident radiologique impactant un grand nombre d'individus, il est primordial de différ... more En cas d'accident radiologique impactant un grand nombre d'individus, il est primordial de différencier rapidement les individus exposés des individus non exposés. Le laboratoire de dosimétrie biologique de l'IRSN développe des méthodes pour répondre à ce type de situation. La méthode de référence est basée sur une estimation rapide de la dose après comptage des dicentriques et des anneaux dans 50 métaphases. À l'issue de cette étape de tri de la population exposée, une estimation plus précise de la dose reçue peut être nécessaire. Cette étape est longue car elle nécessite l'observation des aberrations chromosomiques dans au moins 500 métaphases. Pour améliorer cette méthodologie en deux étapes, nous avons étudié l'utilisation d'un logiciel de détection automatique des dicentriques dans un cas réel d'accident radiologique impliquant 63 victimes. Cette méthode a été comparée aux méthodes manuelles de références. La comparaison des doses obtenues montre que la méthode automatique peut remplacer les deux étapes du comptage manuel (50 et 500 métaphases), car elle cumule les avantages de chacune d'elles : rapidité et précision. ABSTRACT Biological dosimetry in the case of large-scale accidental overexposure to ionising radiation: contribution of the automatic detection of dicentrics. Following large-scale accidental overexposure to ionising radiation, a rapid triage of the exposed population can be performed by scoring dicentrics and ring chromosomes in 50 metaphases. This is rapid but not accurate. Following this triage step, the dose can be estimated by scoring 500 metaphases. This is lengthy but very accurate. To improve the methodology, we propose using software for automatic dicentric scoring, which was tested on 63 victims of a radiological accident. The method using automatic dicentric scoring was compared with the standard methods of manual scoring. The comparison of the doses obtained shows that the automatic method could replace the two steps of the manual scoring (50 and 500 metaphases). In fact, the automatic scoring method is more accurate than the manual scoring of 50 metaphases and can therefore be used for triage.

The worldwide use of sources of ionizing radiation for medical, industrial, research and other pu... more The worldwide use of sources of ionizing radiation for medical, industrial, research and other purposes is inextricably associated with the risk of accidental human exposure. In addition, a constant threat of a nuclear explosion or radiation release, whether during military or terrorist events or as a result of accidents in nuclear power plants keeps raising a possibility of overexposure of the military personnel, workers, and general public to ionizing radiation. As indicated by the recent events at the Fukushima power plant, ongoing terrorist activities, and intelligence information, there is a strong sentiment that it is not a Discussion of if, but when, a radiological or nuclear event materializes. The high potential for the occurrence of such events calls for action plans, guidance, and pre-positioned resources and expertise provided by the defence forces in order to assess, triage and medically manage the exposed individuals and inform commanders’ options for operating in cont...

The worldwide use of sources of ionizing radiation for medical, industrial, research and other pu... more The worldwide use of sources of ionizing radiation for medical, industrial, research and other purposes is inextricably associated with the risk of accidental human exposure. In addition, a constant threat of a nuclear explosion or radiation release, whether during military or terrorist events or as a result of accidents in nuclear power plants keeps raising a possibility of overexposure of the military personnel, workers, and general public to ionizing radiation. As indicated by the recent events at the Fukushima power plant, ongoing terrorist activities, and intelligence information, there is a strong sentiment that it is not a Discussion of if, but when, a radiological or nuclear event materializes. The high potential for the occurrence of such events calls for action plans, guidance, and pre-positioned resources and expertise provided by the defence forces in order to assess, triage and medically manage the exposed individuals and inform commanders’ options for operating in cont...

Genes

Dicentric chromosomes are a relevant marker of chromosomal instability. Their appearance is assoc... more Dicentric chromosomes are a relevant marker of chromosomal instability. Their appearance is associated with telomere dysfunction, leading to cancer progression and a poor clinical outcome. Here, we present Telomere and Centromere staining followed by M-FISH (TC+M-FISH) for improved detection of telomere dysfunction and the identification of dicentric chromosomes in cancer patients and various genetic syndromes. Significant telomere length shortening and significantly higher frequencies of telomere loss and deletion were found in the peripheral lymphocytes of patients with cancer and genetic syndromes relative to similar age-matched healthy donors. We assessed our technique against conventional cytogenetics for the detection of dicentric chromosomes by subjecting metaphase preparations to both approaches. We identified dicentric chromosomes in 28/50 cancer patients and 21/44 genetic syndrome patients using our approach, but only 7/50 and 12/44, respectively, using standard cytogeneti...

International Journal of Radiation Biology, 2016

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

International Journal of Radiation Biology, 2016

Purpose: The European Network of Biological and Physical Retrospective Dosimetry 'RENEB' has cont... more Purpose: The European Network of Biological and Physical Retrospective Dosimetry 'RENEB' has contributed to European radiation emergency preparedness. To give homogeneous dose estimation results, RENEB partners must harmonize their processes. Materials and methods: A first inter-comparison focused on biological and physical dosimetry was used to detect the outliers in terms of dose estimation. Subsequently, trainings were organized to improve both tools dose estimation. A second inter-comparison was performed to validate training efficiency. Simultaneously, based on ISO standards, a QA&QM manual on all dosimetry assays was produced which states a common basis and harmonized procedures for each assay. The evaluation of the agreement of RENEB partners to follow the QA&QM manual was performed through a questionnaire. The integration of new members into the network was carried out in the same way, whatever the assays. Results: The training courses on biological and physical dosimetry were judged to be successful because most of the RENEB members' dose estimates improved in the second inter-comparison. The QA&QM manual describes the consensus for the minimum requirements and the performance criteria for both dosimetry assays. The questionnaire revealed that the whole network capacity currently can manage between 15 and 3800 samples once. Conclusion: The methodology used to harmonize all dosimetry practice within the network RENEB was highly successful. The network is operational to manage a mass casualty radiation accident for immediate dose assessment.

International journal of radiation biology, Jan 10, 2016

Radiation Research, Aug 1, 2005

Previous in vivo studies showed the combination pentoxifylline (PTX) and alpha-tocopherol was hig... more Previous in vivo studies showed the combination pentoxifylline (PTX) and alpha-tocopherol was highly efficient in reducing late radiation-induced skin damage. The present work aimed at investigating the molecular and cellular mechanisms involved in the effects of this combination. Primary cultures of confluent dermal fibroblasts were gamma-irradiated in the presence of PTX and trolox (Tx), the water-soluble analogue of alpha-tocopherol. Drugs were added either before or after radiation exposure and were maintained over time. Their antioxidant capacity and their effect on radiation-induced ROS production was assessed together with cell viability and clonogenicity. DNA damage formation was assessed by the alkaline comet assay and by the micronucleus (MN) test. Cell cycle distribution was also determined. The combination of PTX/ Tx was shown to reduce both immediate and late ROS formation observed in cells after irradiation. Surprisingly, decrease in DNA strand breaks measured by the comet assay was observed any time drugs were added. In addition, the micronucleus test revealed that for cells irradiated with 10 Gy, a late significant increase in MN formation occurred. The combination of PTX/Tx was shown to be antioxidant and to decrease radiation-induced ROS production. The observed effects on DNA damage at any time the drugs were added suggest that PTX/Tx could interfere with the DNA repair process.

CellProfiler pipeline for LR PCC (changes made from original for 2.1.1 version of CellProfiler)

The worldwide use of sources of ionizing radiation for medical, industrial, research and other pu... more The worldwide use of sources of ionizing radiation for medical, industrial, research and other purposes is inextricably associated with the risk of accidental human exposure. In addition, a constant threat of a nuclear explosion or radiation release, whether during military or terrorist events or as a result of accidents in nuclear power plants keeps raising a possibility of overexposure of the military personnel, workers, and general public to ionizing radiation. As indicated by the recent events at the Fukushima power plant, ongoing terrorist activities, and intelligence information, there is a strong sentiment that it is not a Discussion of if, but when, a radiological or nuclear event materializes. The high potential for the occurrence of such events calls for action plans, guidance, and pre-positioned resources and expertise provided by the defence forces in order to assess, triage and medically manage the exposed individuals and inform commanders’ options for operating in cont...

Mutation Research/Genetic Toxicology and Environmental Mutagenesis, 2015

Every year, many countries perform a significant number of investigations based on biological rad... more Every year, many countries perform a significant number of investigations based on biological radiation dose assessment to check suspected or true overexposure by irradiation of radiation workers and individuals of the general population. The scoring of dicentrics in peripheral blood lymphocytes has gradually become the "gold standard" for the biodosimetry-based assessment of accidental situations. Nevertheless, other "classical" biodosimetric methods such as micronuclei, prematurely condensed chromosomes (PCC) and FISH translocations are relevant in some exposure situations, also for surveillance of groups of populations at risk. Historical international intercomparison studies have shown discrepancies among dose-effect curves used to estimate doses from blood samples irradiated between 0 and 4Gy. Recent experimental work performed by the biological dosimetry laboratory of the French Institute for Radiation Protection and Nuclear Safety (IRSN) has shown the impact of some blood harvesting parameters on the mitotic index, and consequently on the quality of dose assessment. Therefore, it was relevant to define the best Quality Assurance (QA) and Quality Control (QC) criteria to harmonize protocols among biodosimetry laboratories. Complementary with several editions of an IAEA technical manual, ISO standards were written with the view of considering the most used chromosome aberrations assays: dicentrics and micronuclei. An important feature of these standards is to address the organization of population triage and laboratories networking that would be required in case of a large nuclear event or malicious act involving radioactive material. These ISO standards are relevant and helpful to implement a coordinated response of several biodosimetry networks in Europe, Japan, Canada, and to support European programs such as MULTIBIODOSE and RENEB. A new important ISO standard on the use of FISH translocations in retrospective dosimetry is now being drafted.

Radioprotection, 2009

Le 36 e congrès annuel de la société européenne de recherche sur les rayonnements (ERRS), l'ERR 2... more Le 36 e congrès annuel de la société européenne de recherche sur les rayonnements (ERRS), l'ERR 2008, a été organisé par une équipe française de l'Institut de radioprotection et de sûreté nucléaire (IRSN), du 1 er au 4 septembre 2008, à Tours (France). Ce congrès a rassemblé plus de 150 chercheurs et médecins venus du monde entier. Au-delà de ces chiffres, ce congrès a mis en avant plusieurs thèmes de recherche majeurs à l'heure actuelle et notamment la dosimétrie biologique, l'instabilité génétique et les effets de voisinage, et les dommages aux tissus sains. L'épidémiologie était également pour la première fois présente dans un congrès de l'ERRS. L'objectif de cet article est de faire un tour d'horizon rapide des résultats marquants présentés durant ce congrès. ABSTRACT The 36th annual meeting of the European radiation research society (ERRS): an overview of radiation biology. The 36th annual meeting of the European Radiation Research Society (ERRS), the ERR 2008 meeting, was organized by a team from the French Radiation protection and nuclear safety institute (IRSN) in Tours (France), from September 1st to 4th, 2008. More than 150 researchers and physicians, coming from all over the world participated in this meeting. Beyond these data, this meeting highlighted several major fields of research, among which biological dosimetry, genetic instability and bystander effects, and normal tissue damages. Epidemiological studies were also represented for the first time in an ERRS meeting. The goal of this paper is to present an overview of major results presented during this meeting.

Military medicine, 2002

The capability to make diagnostic assessments of radiation exposure is needed to support triage o... more The capability to make diagnostic assessments of radiation exposure is needed to support triage of radiation casualties and medical treatment decisions in military operations. At the International Conference on Low-Level Radiation Injury and Medical Countermeasures session on biodosimetry in the military, participants reviewed the field of biomarkers, covering a wide range of biological endpoints. Participants evaluated early changes associated with exposure to ionizing radiation, including chromosomal and DNA damage, gene expression and associated proteins, and DNA mutations. The use and development of advanced monitoring and diagnostic technologies compatible with military operations was emphasized. Conventional radiation bioassays require a substantial amount of time between when the sample is taken and when the data can be provided for decision making. These "reach back" bioassays are evaluated in laboratories that are not in the field; these laboratories routinely mea...

Current Topics in Ionizing Radiation Research, 2012

Current Topics in Ionizing Radiation Research, 2012

Nevertheless, these bioindicators have many limitations. Currently, a lot of research is performe... more Nevertheless, these bioindicators have many limitations. Currently, a lot of research is performed to find new indicators of exposure (such as H2AX and gene expression) (Figure 1). It is important to note that there are several essential requirements for biological parameters as meaningful dosimeters: low background level, clear dose-effect relationship for different radiation qualities and dose rates, specificity to ionizing radiation, noninvasive, fast availability of dose estimate, good reproducibility and comparability of in vitro and in vivo results (Romm, 2009). Gene expression profil γH2AX foci yield Dicentric Centric Ring Acentric fragment Micronucleus Centromere-positive Centromere-negative Micronucleus Micronucleus Unstable chromosome aberrations =Recent exposure Early variations Very early signalization Damage signalization modulation of gene expression Misrepair Stable chromosome aberrations =Old exposure Two-way One-way Insertion Translocation Translocation Gene expression profil γH2AX foci yield Dicentric Centric Ring Acentric fragment Micronucleus Centromere-positive Centromere-negative Micronucleus Micronucleus

Cytometry, 1998

Fluorescence in situ hybridization (FISH) has become a powerful tool in chromosome analysis. This... more Fluorescence in situ hybridization (FISH) has become a powerful tool in chromosome analysis. This report describes the systematic optimization of the Fast-FISH technique for centromere labeling of human metaphase chromosomes for radiobiological dosimetry purposes. For the present study, the hybridization conditions and the efficiency of two commercially available alpha-satellite DNA probes were compared ("human chromosome 1 specific", Oncor, Gaithersburg, MD, vs. "all-human chromosomes specific", Boehringer-Mannheim, Germany). These probes were hybridized to human lymphocyte metaphase plates by using a hybridization buffer without formamide and without any other equivalent denaturing chemical agents. The results indicate the suitability of the method for automated image analysis on the basis of thresholding. The optimal conditions concerning hybridization time and temperature were determined by a systematic quantitative evaluation of the fluorescent labeling sites after the hybridization procedures. Under defined "low stringency" conditions, we found that the "human chromosome 1 specific" DNA probe labeled not only the centromere of the human chromosome 1 but also the other human centromeres in the same way as the "all-human chromosome specific" DNA probe. The optimized conditions to complete all centromere labeling were applied to the detection of dicentric chromosomes on irradiated human lymphocyte samples (gamma-rays of 60Co source, 0.5 Gy/min, for doses of 1, 3, and 4 Gy). The yield of dicentrics was determined after Fast-FISH and compared with results obtained after Giemsa staining. These results are very compatible and indicate that, because of its simplicity, this optimized Fast-FISH procedure would be useful for fast screening purposes in biological dosimetry after accidental overexposure.

Radioprotection, 2006

De nombreuses études suggèrent que les cellules souches adultes et plus particulièrement les cell... more De nombreuses études suggèrent que les cellules souches adultes et plus particulièrement les cellules souches Mésenchymateuses humaines (CSMh) pourraient être utilisées pour réparer de nombreux organes. Nous avons étudié la capacité des CSMh à réduire les lésions cutanées radio induite. Pour induire des lésions sévères de la peau, des souris NOD/SCID ont été irradiées au niveau de la patte droite postérieure (30 Gy, débit 2,7 Gy/mn) en utilisant une source gamma au 60 Co. Les CSMh ont été injectées 24 heures après irradiation par voie intraveineuse. La présence de cellules humaines, la sévérité des lésions et les processus de cicatrisation ont été étudiés sur les échantillons de peau prélevés de 3 à 8 semaines après irradiation. Nous avons pu observer que chez les souris greffées avec des CSMh, le niveau d'atteinte cutanée radio induite est significativement plus faible. Les scores cliniques utilisés pour l'étude de l'évolution des lésions cutanées de la peau sont significativement améliorés et une cicatrisation plus rapide est observée en comparaison des souris non injectées. La présence de cellules humaines a pu être détectée par PCR quantitative dans les zones cutanées en cours de cicatrisation. Ces résultats suggèrent premièrement que les CSMh sont capables de coloniser la peau altérée par les rayonnements ionisants et deuxièmement qu'elles accélèrent le processus de réparation de ce tissu limitant ainsi les complications tissulaires radio induites. La greffe de CSMh pourrait être un traitement thérapeutique efficace des phases précoces du syndrome cutané radio induit ABSTRACT Mesenchymal stem cells favour healing of the cutaneous radiation syndrome.

Journal of Radiation Research, 2001

Because of the large number of cells to be analyzed in cases of overexposure to ionizing radiatio... more Because of the large number of cells to be analyzed in cases of overexposure to ionizing radiation, an automated imaging system is desirable for scoring both translocations and dicentrics. This system should include three essential steps: automatic metaphase finding, automatic image capture at high magnification, and, finally, optimized data analysis for aberration interpretation. We evaluated a new image analysis system (CYTOGEN, IMSTAR, France) and found that its metaphase finder saved time, as much as quadrupling the speed of scoring chromosomal aberrations. Automatic metaphase selection did not appear to induce bias. We confirmed the equivalence of observing aberrations on a screen after automatic image capture and direct observation under a microscope. This work validated all of the steps necessary for obtaining images for automatic chromosomal aberration detection. The protocols for the detection of translocations may now be applied for biological dosimetry. This step will be validated in a future study.

Radioprotection, 2010

En cas d'accident radiologique impactant un grand nombre d'individus, il est primordial de différ... more En cas d'accident radiologique impactant un grand nombre d'individus, il est primordial de différencier rapidement les individus exposés des individus non exposés. Le laboratoire de dosimétrie biologique de l'IRSN développe des méthodes pour répondre à ce type de situation. La méthode de référence est basée sur une estimation rapide de la dose après comptage des dicentriques et des anneaux dans 50 métaphases. À l'issue de cette étape de tri de la population exposée, une estimation plus précise de la dose reçue peut être nécessaire. Cette étape est longue car elle nécessite l'observation des aberrations chromosomiques dans au moins 500 métaphases. Pour améliorer cette méthodologie en deux étapes, nous avons étudié l'utilisation d'un logiciel de détection automatique des dicentriques dans un cas réel d'accident radiologique impliquant 63 victimes. Cette méthode a été comparée aux méthodes manuelles de références. La comparaison des doses obtenues montre que la méthode automatique peut remplacer les deux étapes du comptage manuel (50 et 500 métaphases), car elle cumule les avantages de chacune d'elles : rapidité et précision. ABSTRACT Biological dosimetry in the case of large-scale accidental overexposure to ionising radiation: contribution of the automatic detection of dicentrics. Following large-scale accidental overexposure to ionising radiation, a rapid triage of the exposed population can be performed by scoring dicentrics and ring chromosomes in 50 metaphases. This is rapid but not accurate. Following this triage step, the dose can be estimated by scoring 500 metaphases. This is lengthy but very accurate. To improve the methodology, we propose using software for automatic dicentric scoring, which was tested on 63 victims of a radiological accident. The method using automatic dicentric scoring was compared with the standard methods of manual scoring. The comparison of the doses obtained shows that the automatic method could replace the two steps of the manual scoring (50 and 500 metaphases). In fact, the automatic scoring method is more accurate than the manual scoring of 50 metaphases and can therefore be used for triage.

The worldwide use of sources of ionizing radiation for medical, industrial, research and other pu... more The worldwide use of sources of ionizing radiation for medical, industrial, research and other purposes is inextricably associated with the risk of accidental human exposure. In addition, a constant threat of a nuclear explosion or radiation release, whether during military or terrorist events or as a result of accidents in nuclear power plants keeps raising a possibility of overexposure of the military personnel, workers, and general public to ionizing radiation. As indicated by the recent events at the Fukushima power plant, ongoing terrorist activities, and intelligence information, there is a strong sentiment that it is not a Discussion of if, but when, a radiological or nuclear event materializes. The high potential for the occurrence of such events calls for action plans, guidance, and pre-positioned resources and expertise provided by the defence forces in order to assess, triage and medically manage the exposed individuals and inform commanders’ options for operating in cont...

The worldwide use of sources of ionizing radiation for medical, industrial, research and other pu... more The worldwide use of sources of ionizing radiation for medical, industrial, research and other purposes is inextricably associated with the risk of accidental human exposure. In addition, a constant threat of a nuclear explosion or radiation release, whether during military or terrorist events or as a result of accidents in nuclear power plants keeps raising a possibility of overexposure of the military personnel, workers, and general public to ionizing radiation. As indicated by the recent events at the Fukushima power plant, ongoing terrorist activities, and intelligence information, there is a strong sentiment that it is not a Discussion of if, but when, a radiological or nuclear event materializes. The high potential for the occurrence of such events calls for action plans, guidance, and pre-positioned resources and expertise provided by the defence forces in order to assess, triage and medically manage the exposed individuals and inform commanders’ options for operating in cont...

Genes

Dicentric chromosomes are a relevant marker of chromosomal instability. Their appearance is assoc... more Dicentric chromosomes are a relevant marker of chromosomal instability. Their appearance is associated with telomere dysfunction, leading to cancer progression and a poor clinical outcome. Here, we present Telomere and Centromere staining followed by M-FISH (TC+M-FISH) for improved detection of telomere dysfunction and the identification of dicentric chromosomes in cancer patients and various genetic syndromes. Significant telomere length shortening and significantly higher frequencies of telomere loss and deletion were found in the peripheral lymphocytes of patients with cancer and genetic syndromes relative to similar age-matched healthy donors. We assessed our technique against conventional cytogenetics for the detection of dicentric chromosomes by subjecting metaphase preparations to both approaches. We identified dicentric chromosomes in 28/50 cancer patients and 21/44 genetic syndrome patients using our approach, but only 7/50 and 12/44, respectively, using standard cytogeneti...

International Journal of Radiation Biology, 2016

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

International Journal of Radiation Biology, 2016

Purpose: The European Network of Biological and Physical Retrospective Dosimetry 'RENEB' has cont... more Purpose: The European Network of Biological and Physical Retrospective Dosimetry 'RENEB' has contributed to European radiation emergency preparedness. To give homogeneous dose estimation results, RENEB partners must harmonize their processes. Materials and methods: A first inter-comparison focused on biological and physical dosimetry was used to detect the outliers in terms of dose estimation. Subsequently, trainings were organized to improve both tools dose estimation. A second inter-comparison was performed to validate training efficiency. Simultaneously, based on ISO standards, a QA&QM manual on all dosimetry assays was produced which states a common basis and harmonized procedures for each assay. The evaluation of the agreement of RENEB partners to follow the QA&QM manual was performed through a questionnaire. The integration of new members into the network was carried out in the same way, whatever the assays. Results: The training courses on biological and physical dosimetry were judged to be successful because most of the RENEB members' dose estimates improved in the second inter-comparison. The QA&QM manual describes the consensus for the minimum requirements and the performance criteria for both dosimetry assays. The questionnaire revealed that the whole network capacity currently can manage between 15 and 3800 samples once. Conclusion: The methodology used to harmonize all dosimetry practice within the network RENEB was highly successful. The network is operational to manage a mass casualty radiation accident for immediate dose assessment.

International journal of radiation biology, Jan 10, 2016

Radiation Research, Aug 1, 2005

Previous in vivo studies showed the combination pentoxifylline (PTX) and alpha-tocopherol was hig... more Previous in vivo studies showed the combination pentoxifylline (PTX) and alpha-tocopherol was highly efficient in reducing late radiation-induced skin damage. The present work aimed at investigating the molecular and cellular mechanisms involved in the effects of this combination. Primary cultures of confluent dermal fibroblasts were gamma-irradiated in the presence of PTX and trolox (Tx), the water-soluble analogue of alpha-tocopherol. Drugs were added either before or after radiation exposure and were maintained over time. Their antioxidant capacity and their effect on radiation-induced ROS production was assessed together with cell viability and clonogenicity. DNA damage formation was assessed by the alkaline comet assay and by the micronucleus (MN) test. Cell cycle distribution was also determined. The combination of PTX/ Tx was shown to reduce both immediate and late ROS formation observed in cells after irradiation. Surprisingly, decrease in DNA strand breaks measured by the comet assay was observed any time drugs were added. In addition, the micronucleus test revealed that for cells irradiated with 10 Gy, a late significant increase in MN formation occurred. The combination of PTX/Tx was shown to be antioxidant and to decrease radiation-induced ROS production. The observed effects on DNA damage at any time the drugs were added suggest that PTX/Tx could interfere with the DNA repair process.

CellProfiler pipeline for LR PCC (changes made from original for 2.1.1 version of CellProfiler)

The worldwide use of sources of ionizing radiation for medical, industrial, research and other pu... more The worldwide use of sources of ionizing radiation for medical, industrial, research and other purposes is inextricably associated with the risk of accidental human exposure. In addition, a constant threat of a nuclear explosion or radiation release, whether during military or terrorist events or as a result of accidents in nuclear power plants keeps raising a possibility of overexposure of the military personnel, workers, and general public to ionizing radiation. As indicated by the recent events at the Fukushima power plant, ongoing terrorist activities, and intelligence information, there is a strong sentiment that it is not a Discussion of if, but when, a radiological or nuclear event materializes. The high potential for the occurrence of such events calls for action plans, guidance, and pre-positioned resources and expertise provided by the defence forces in order to assess, triage and medically manage the exposed individuals and inform commanders’ options for operating in cont...

Mutation Research/Genetic Toxicology and Environmental Mutagenesis, 2015

Every year, many countries perform a significant number of investigations based on biological rad... more Every year, many countries perform a significant number of investigations based on biological radiation dose assessment to check suspected or true overexposure by irradiation of radiation workers and individuals of the general population. The scoring of dicentrics in peripheral blood lymphocytes has gradually become the "gold standard" for the biodosimetry-based assessment of accidental situations. Nevertheless, other "classical" biodosimetric methods such as micronuclei, prematurely condensed chromosomes (PCC) and FISH translocations are relevant in some exposure situations, also for surveillance of groups of populations at risk. Historical international intercomparison studies have shown discrepancies among dose-effect curves used to estimate doses from blood samples irradiated between 0 and 4Gy. Recent experimental work performed by the biological dosimetry laboratory of the French Institute for Radiation Protection and Nuclear Safety (IRSN) has shown the impact of some blood harvesting parameters on the mitotic index, and consequently on the quality of dose assessment. Therefore, it was relevant to define the best Quality Assurance (QA) and Quality Control (QC) criteria to harmonize protocols among biodosimetry laboratories. Complementary with several editions of an IAEA technical manual, ISO standards were written with the view of considering the most used chromosome aberrations assays: dicentrics and micronuclei. An important feature of these standards is to address the organization of population triage and laboratories networking that would be required in case of a large nuclear event or malicious act involving radioactive material. These ISO standards are relevant and helpful to implement a coordinated response of several biodosimetry networks in Europe, Japan, Canada, and to support European programs such as MULTIBIODOSE and RENEB. A new important ISO standard on the use of FISH translocations in retrospective dosimetry is now being drafted.

Radioprotection, 2009

Le 36 e congrès annuel de la société européenne de recherche sur les rayonnements (ERRS), l'ERR 2... more Le 36 e congrès annuel de la société européenne de recherche sur les rayonnements (ERRS), l'ERR 2008, a été organisé par une équipe française de l'Institut de radioprotection et de sûreté nucléaire (IRSN), du 1 er au 4 septembre 2008, à Tours (France). Ce congrès a rassemblé plus de 150 chercheurs et médecins venus du monde entier. Au-delà de ces chiffres, ce congrès a mis en avant plusieurs thèmes de recherche majeurs à l'heure actuelle et notamment la dosimétrie biologique, l'instabilité génétique et les effets de voisinage, et les dommages aux tissus sains. L'épidémiologie était également pour la première fois présente dans un congrès de l'ERRS. L'objectif de cet article est de faire un tour d'horizon rapide des résultats marquants présentés durant ce congrès. ABSTRACT The 36th annual meeting of the European radiation research society (ERRS): an overview of radiation biology. The 36th annual meeting of the European Radiation Research Society (ERRS), the ERR 2008 meeting, was organized by a team from the French Radiation protection and nuclear safety institute (IRSN) in Tours (France), from September 1st to 4th, 2008. More than 150 researchers and physicians, coming from all over the world participated in this meeting. Beyond these data, this meeting highlighted several major fields of research, among which biological dosimetry, genetic instability and bystander effects, and normal tissue damages. Epidemiological studies were also represented for the first time in an ERRS meeting. The goal of this paper is to present an overview of major results presented during this meeting.

Military medicine, 2002

The capability to make diagnostic assessments of radiation exposure is needed to support triage o... more The capability to make diagnostic assessments of radiation exposure is needed to support triage of radiation casualties and medical treatment decisions in military operations. At the International Conference on Low-Level Radiation Injury and Medical Countermeasures session on biodosimetry in the military, participants reviewed the field of biomarkers, covering a wide range of biological endpoints. Participants evaluated early changes associated with exposure to ionizing radiation, including chromosomal and DNA damage, gene expression and associated proteins, and DNA mutations. The use and development of advanced monitoring and diagnostic technologies compatible with military operations was emphasized. Conventional radiation bioassays require a substantial amount of time between when the sample is taken and when the data can be provided for decision making. These "reach back" bioassays are evaluated in laboratories that are not in the field; these laboratories routinely mea...

Current Topics in Ionizing Radiation Research, 2012

Current Topics in Ionizing Radiation Research, 2012

Nevertheless, these bioindicators have many limitations. Currently, a lot of research is performe... more Nevertheless, these bioindicators have many limitations. Currently, a lot of research is performed to find new indicators of exposure (such as H2AX and gene expression) (Figure 1). It is important to note that there are several essential requirements for biological parameters as meaningful dosimeters: low background level, clear dose-effect relationship for different radiation qualities and dose rates, specificity to ionizing radiation, noninvasive, fast availability of dose estimate, good reproducibility and comparability of in vitro and in vivo results (Romm, 2009). Gene expression profil γH2AX foci yield Dicentric Centric Ring Acentric fragment Micronucleus Centromere-positive Centromere-negative Micronucleus Micronucleus Unstable chromosome aberrations =Recent exposure Early variations Very early signalization Damage signalization modulation of gene expression Misrepair Stable chromosome aberrations =Old exposure Two-way One-way Insertion Translocation Translocation Gene expression profil γH2AX foci yield Dicentric Centric Ring Acentric fragment Micronucleus Centromere-positive Centromere-negative Micronucleus Micronucleus

Cytometry, 1998

Fluorescence in situ hybridization (FISH) has become a powerful tool in chromosome analysis. This... more Fluorescence in situ hybridization (FISH) has become a powerful tool in chromosome analysis. This report describes the systematic optimization of the Fast-FISH technique for centromere labeling of human metaphase chromosomes for radiobiological dosimetry purposes. For the present study, the hybridization conditions and the efficiency of two commercially available alpha-satellite DNA probes were compared ("human chromosome 1 specific", Oncor, Gaithersburg, MD, vs. "all-human chromosomes specific", Boehringer-Mannheim, Germany). These probes were hybridized to human lymphocyte metaphase plates by using a hybridization buffer without formamide and without any other equivalent denaturing chemical agents. The results indicate the suitability of the method for automated image analysis on the basis of thresholding. The optimal conditions concerning hybridization time and temperature were determined by a systematic quantitative evaluation of the fluorescent labeling sites after the hybridization procedures. Under defined "low stringency" conditions, we found that the "human chromosome 1 specific" DNA probe labeled not only the centromere of the human chromosome 1 but also the other human centromeres in the same way as the "all-human chromosome specific" DNA probe. The optimized conditions to complete all centromere labeling were applied to the detection of dicentric chromosomes on irradiated human lymphocyte samples (gamma-rays of 60Co source, 0.5 Gy/min, for doses of 1, 3, and 4 Gy). The yield of dicentrics was determined after Fast-FISH and compared with results obtained after Giemsa staining. These results are very compatible and indicate that, because of its simplicity, this optimized Fast-FISH procedure would be useful for fast screening purposes in biological dosimetry after accidental overexposure.