Use of the γ-H2AX Assay to Investigate DNA Repair Dynamics Following Multiple Radiation Exposures

Radiation therapy is one of the most common and effective strategies used to treat cancer. The irradiation is usually performed with a fractionated scheme, where the dose required to kill tumour cells is given in several sessions, spaced by specific time intervals, to allow healthy tissue recovery....

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Published in:PloS one Vol. 8; no. 11; p. e79541
Main Authors: Mariotti, Luca G., Pirovano, Giacomo, Savage, Kienan I., Ghita, Mihaela, Ottolenghi, Andrea, Prise, Kevin M., Schettino, Giuseppe
Format: Journal Article
Language:English
Published: United States Public Library of Science 29.11.2013
Public Library of Science (PLoS)
Subjects:
Apoptosis
Biology
Cancer
Cell cycle
Cell Line
Cell survival
Cell Survival - radiation effects
Chromatin
Chromatin - radiation effects
Deoxyribonucleic acid
DNA
DNA Damage
DNA repair
DNA Repair - radiation effects
Dose-Response Relationship, Radiation
Dynamic tests
Exposure
Fibroblasts
Fibroblasts - metabolism
Fibroblasts - radiation effects
Histones - metabolism
Humans
Irradiation
Kinases
Medical research
Oncology
Order parameters
Phosphatase
Phosphorylation
Proteins
Radiation
Radiation Dosage
Radiation effects
Radiation therapy
Radiotherapy - adverse effects
Recovery
Repair
Tumors
X-Rays - adverse effects
United Kingdom > UK
Italy
ISSN:1932-6203, 1932-6203
Online Access:Get full text
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Summary:Radiation therapy is one of the most common and effective strategies used to treat cancer. The irradiation is usually performed with a fractionated scheme, where the dose required to kill tumour cells is given in several sessions, spaced by specific time intervals, to allow healthy tissue recovery. In this work, we examined the DNA repair dynamics of cells exposed to radiation delivered in fractions, by assessing the response of histone-2AX (H2AX) phosphorylation (γ-H2AX), a marker of DNA double strand breaks. γ-H2AX foci induction and disappearance were monitored following split dose irradiation experiments in which time interval between exposure and dose were varied. Experimental data have been coupled to an analytical theoretical model, in order to quantify key parameters involved in the foci induction process. Induction of γ-H2AX foci was found to be affected by the initial radiation exposure with a smaller number of foci induced by subsequent exposures. This was compared to chromatin relaxation and cell survival. The time needed for full recovery of γ-H2AX foci induction was quantified (12 hours) and the 1:1 relationship between radiation induced DNA double strand breaks and foci numbers was critically assessed in the multiple irradiation scenarios.
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Current address: Department of Oncology, Gray Institute for Radiation Oncology and Biology, University of Oxford Oxford, United Kingdom
Competing Interests: The authors have declared that no competing interests exist.
Conceived and designed the experiments: LGM GS GP. Performed the experiments: GP MG KIS. Analyzed the data: LGM GS AO. Contributed reagents/materials/analysis tools: KMP. Wrote the manuscript: LGM GP GS.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0079541