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

Détails

ID Serval
serval:BIB_275D608E4036
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Influence of Nucleoshuttling of the ATM Protein in the Healthy Tissues Response to Radiation Therapy: Toward a Molecular Classification of Human Radiosensitivity.
Périodique
International Journal of Radiation Oncology, Biology, Physics
Auteur(s)
Granzotto A., Granzotto A., Benadjaoud M.A., Vogin G., Devic C., Ferlazzo M.L., Bodgi L., Pereira S., Sonzogni L., Forcheron F., Viau M., Etaix A., Malek K., Mengue-Bindjeme L., Escoffier C., Rouvet I., Zabot M.T., Joubert A., Vincent A., Dalla Venezia N., Bourguignon M., Canat E.P., d'Hombres A., Thébaud E., Orbach D., Stoppa-Lyonnet D., Radji A., Doré E., Pointreau Y., Bourgier C., Leblond P., Defachelles A.S., Lervat C., Guey S., Feuvret L., Gilsoul F., Berger C., Moncharmont C., de Laroche G., Moreau-Claeys M.V., Chavaudra N., Combemale P., Biston M.C., Malet C., Martel-Lafay I., Laude C., Hau-Desbat N.H., Ziouéche A., Tanguy R., Sunyach M.P., Racadot S., Pommier P., Claude L., Baleydier F., Fleury B., de Crevoisier R., Simon J.M., Verrelle P., Peiffert D., Belkacemi Y., Bourhis J., Lartigau E., Carrie C., De Vathaire F., Eschwege F., Puisieux A., Lagrange J.L., Balosso J., Foray N.
Collaborateur(s)
COPERNIC project investigators
ISSN
1879-355X (Electronic)
ISSN-L
0360-3016
Statut éditorial
Publié
Date de publication
2016
Peer-reviewed
Oui
Volume
94
Numéro
3
Pages
450-460
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: ppublish
Résumé
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).
Mots-clé
Analysis of Variance, Ataxia Telangiectasia Mutated Proteins/genetics, Ataxia Telangiectasia Mutated Proteins/metabolism, Biopsy, Cell Line, Cell Nucleus/metabolism, DNA Breaks, Double-Stranded, DNA Repair, Fibroblasts/radiation effects, Histones/metabolism, Humans, Micronucleus Tests/methods, Phosphorylation, Radiation Injuries/classification, Radiation Injuries/metabolism, Radiation Tolerance/genetics, Radiation Tolerance/physiology, Skin/pathology, Skin/radiation effects, Time Factors
Pubmed
Web of science
Création de la notice
20/02/2016 17:06
Dernière modification de la notice
20/08/2019 13:06
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