Enhancement of IUdR Radiosensitization by Low-Energy Photons Results from Increased and Persistent DNA Damage.

Détails

Ressource 1Télécharger: journal.pone.0168395.pdf (1344.08 [Ko])
Etat: Public
Version: Final published version
ID Serval
serval:BIB_CE2E9E7C7B50
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Enhancement of IUdR Radiosensitization by Low-Energy Photons Results from Increased and Persistent DNA Damage.
Périodique
PloS one
Auteur(s)
Bayart E., Pouzoulet F., Calmels L., Dadoun J., Allot F., Plagnard J., Ravanat J.L., Bridier A., Denozière M., Bourhis J., Deutsch E.
ISSN
1932-6203 (Electronic)
ISSN-L
1932-6203
Statut éditorial
Publié
Date de publication
2017
Peer-reviewed
Oui
Volume
12
Numéro
1
Pages
e0168395
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: epublish
Résumé
Low-energy X-rays induce Auger cascades by photoelectric absorption in iodine present in the DNA of cells labeled with 5-iodo-2'-deoxyuridine (IUdR). This photoactivation therapy results in enhanced cellular sensitivity to radiation which reaches its maximum with 50 keV photons. Synchrotron core facilities are the only way to generate such monochromatic beams. However, these structures are not adapted for the routine treatment of patients. In this study, we generated two beams emitting photon energy means of 42 and 50 keV respectively, from a conventional 225 kV X-ray source. Viability assays performed after pre-exposure to 10 μM of IUdR for 48h suggest that complex lethal damage is generated after low energy photons irradiation compared to 137Cs irradiation (662KeV). To further decipher the molecular mechanisms leading to IUdR-mediated radiosensitization, we analyzed the content of DNA damage-induced foci in two glioblastoma cell lines and showed that the decrease in survival under these conditions was correlated with an increase in the content of DNA damage-induced foci in cell lines. Moreover, the follow-up of repair kinetics of the induced double-strand breaks showed the maximum delay in cells labeled with IUdR and exposed to X-ray irradiation. Thus, there appears to be a direct relationship between the reduction of radiation survival parameters and the production of DNA damage with impaired repair of these breaks. These results further support the clinical potential use of a halogenated pyrimidine analog combined with low-energy X-ray therapy.

Mots-clé
Animals, Cell Line, Tumor, Cell Survival/drug effects, Cesium Radioisotopes, DNA Damage/drug effects, Dose-Response Relationship, Radiation, Humans, Idoxuridine/pharmacology, Kinetics, Photons, Radiation Tolerance/drug effects, Radiation-Sensitizing Agents/pharmacology, Rats, Synchrotrons, Tumor Suppressor p53-Binding Protein 1/metabolism, X-Rays
Pubmed
Web of science
Open Access
Oui
Création de la notice
10/01/2017 17:58
Dernière modification de la notice
20/08/2019 15:48
Données d'usage