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Influence of Nucleoshuttling of the ATM Protein in the Healthy Tissues Response to Radiation Therapy: Toward a Molecular Classification of Human Radiosensitivity.
Journal article

Influence of Nucleoshuttling of the ATM Protein in the Healthy Tissues Response to Radiation Therapy: Toward a Molecular Classification of Human Radiosensitivity.

  • Granzotto A INSERM UMRS 1018, Institut Gustave-Roussy, Villejuif, France.
  • Benadjaoud MA INSERM, UMR1052, Cancer Research Centre of Lyon, Lyon, France; Institut de Cancérologie de Lorraine, Vandoeuvre-les-Nancy, France.
  • Vogin G INSERM, UMR1052, Cancer Research Centre of Lyon, Lyon, France.
  • Devic C INSERM, UMR1052, Cancer Research Centre of Lyon, Lyon, France.
  • Ferlazzo ML INSERM, UMR1052, Cancer Research Centre of Lyon, Lyon, France; Université Saint-Joseph, Beirut, Lebanon.
  • Bodgi L INSERM, UMR1052, Cancer Research Centre of Lyon, Lyon, France.
  • Pereira S INSERM, UMR1052, Cancer Research Centre of Lyon, Lyon, France.
  • Sonzogni L Institut de Recherche Biomédicale des Armées, Brétigny-sur-Orge, France.
  • Forcheron F INSERM, UMR1052, Cancer Research Centre of Lyon, Lyon, France.
  • Viau M INSERM, UMR1052, Cancer Research Centre of Lyon, Lyon, France.
  • Etaix A INSERM, UMR1052, Cancer Research Centre of Lyon, Lyon, France.
  • Malek K INSERM, UMR1052, Cancer Research Centre of Lyon, Lyon, France.
  • Mengue-Bindjeme L Centre de Biotechnologie Cellulaire et Biothèque, Groupement Hospitalier Est, Hospices Civils de Lyon, Bron, France.
  • Escoffier C Centre de Biotechnologie Cellulaire et Biothèque, Groupement Hospitalier Est, Hospices Civils de Lyon, Bron, France.
  • Rouvet I Centre de Biotechnologie Cellulaire et Biothèque, Groupement Hospitalier Est, Hospices Civils de Lyon, Bron, France.
  • Zabot MT Institut de Radioprotection et de Sûreté Nucléaire, Fontenay-aux-Roses, France.
  • Joubert A INSERM, UMR1052, Cancer Research Centre of Lyon, Lyon, France.
  • Vincent A INSERM, UMR1052, Cancer Research Centre of Lyon, Lyon, France.
  • Dalla Venezia N Institut de Radioprotection et de Sûreté Nucléaire, Fontenay-aux-Roses, France.
  • Bourguignon M Clinique Jean-Mermoz, Lyon, France.
  • Canat EP Groupement Hospitalier Sud, Hospices Civils de Lyon, Pierre-Bénite, France.
  • d'Hombres A Centre Hospitalier Universitaire, Nantes, France.
  • Thébaud E Institut Curie, Paris, France.
  • Orbach D Institut Curie, Paris, France.
  • Stoppa-Lyonnet D Centre Joliot-Curie, Rouen, France.
  • Radji A Centre Hospitalier Universitaire, Clermont-Ferrand, France.
  • Doré E Centre Hospitalier Régional Universitaire Bretonneau, Tours, France.
  • Pointreau Y Institut du Val d'Aurelle, Montpellier, France.
  • Bourgier C Centre Oscar-Lambret, Lille, France.
  • Leblond P Centre Oscar-Lambret, Lille, France.
  • Defachelles AS Centre Oscar-Lambret, Lille, France.
  • Lervat C Hôpital La Pitié-Salpétrière, Assistance Publique des Hôpitaux de Paris, Paris, France.
  • Guey S Hôpital La Pitié-Salpétrière, Assistance Publique des Hôpitaux de Paris, Paris, France.
  • Feuvret L Hôpital Saint Joseph, Charleroi, Belgique.
  • Gilsoul F Centre Hospitalier Universitaire, Saint-Etienne, France.
  • Berger C Centre Hospitalier Universitaire, Saint-Etienne, France.
  • Moncharmont C Centre Hospitalier Universitaire, Saint-Etienne, France.
  • de Laroche G Institut de Cancérologie de Lorraine, Vandoeuvre-les-Nancy, France.
  • Moreau-Claeys MV Institut Gustave-Roussy, Villejuif, France.
  • Chavaudra N Centre Léon-Bérard, Lyon, France.
  • Combemale P Centre Léon-Bérard, Lyon, France.
  • Biston MC Centre Léon-Bérard, Lyon, France.
  • Malet C Centre Léon-Bérard, Lyon, France.
  • Martel-Lafay I Centre Léon-Bérard, Lyon, France.
  • Laude C Centre Léon-Bérard, Lyon, France; Centre Hospitalier Métropôle-Savoie, Chambéry, France.
  • Hau-Desbat NH Centre Léon-Bérard, Lyon, France.
  • Ziouéche A Centre Léon-Bérard, Lyon, France.
  • Tanguy R Centre Léon-Bérard, Lyon, France.
  • Sunyach MP Centre Léon-Bérard, Lyon, France.
  • Racadot S Centre Léon-Bérard, Lyon, France.
  • Pommier P Centre Léon-Bérard, Lyon, France.
  • Claude L Institut d'Hématologie et d'Oncologie Pédiatrique, Hospices Civils de Lyon, Lyon, France.
  • Baleydier F Centre Marie Curie, Valence, France.
  • Fleury B Centre Eugène-Marquis, Rennes, France.
  • de Crevoisier R Hôpital La Pitié-Salpétrière, Assistance Publique des Hôpitaux de Paris, Paris, France.
  • Simon JM Institut Curie, Paris, France; Centre Jean-Perrin, Clermont-Ferrand, France.
  • Verrelle P Institut de Cancérologie de Lorraine, Vandoeuvre-les-Nancy, France.
  • Peiffert D Hôpital Henri-Mondor, Assistance Publique des Hôpitaux de Paris, Créteil, France.
  • Belkacemi Y Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
  • Bourhis J Centre Oscar-Lambret, Lille, France.
  • Lartigau E Centre Léon-Bérard, Lyon, France.
  • Carrie C Institut de Cancérologie de Lorraine, Vandoeuvre-les-Nancy, France.
  • De Vathaire F Institut Gustave-Roussy, Villejuif, France.
  • Eschwege F INSERM, UMR1052, Cancer Research Centre of Lyon, Lyon, France.
  • Puisieux A Hôpital Henri-Mondor, Assistance Publique des Hôpitaux de Paris, Créteil, France.
  • Lagrange JL Centre Hospitalier Universitaire, Grenoble, France.
  • Balosso J INSERM, UMR1052, Cancer Research Centre of Lyon, Lyon, France. Electronic address: Nicolas.foray@inserm.fr.
  • Foray N
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  • 2016-02-13
Published in:
  • International journal of radiation oncology, biology, physics. - 2016
Analysis of Variance
Ataxia Telangiectasia Mutated Proteins
Biopsy
Cell Line
Cell Nucleus
DNA Breaks, Double-Stranded
DNA Repair
Fibroblasts
Histones
Humans
Micronucleus Tests
Phosphorylation
Radiation Injuries
Radiation Tolerance
Skin
Time Factors
English 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).
Language
  • English
Open access status
closed
Identifiers
Persistent URL
https://sonar.ch/global/documents/25259
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