Rejoining of DNA double-strand breaks in X-irradiated CHO cells studied by constant- and graded-field gel electrophoresis

Dahm-Daphi, Jochen; Dikomey, Ekkehard

doi:10.1080/095530096145625

Cited by 41 publications

(12 citation statements)

References 27 publications

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“…In the latter, a tendency toward a quadratic increase is observed. Similar results have been obtained also with the use of gel electrophoresis techniques by different groups [52,53]. Of particular interest in this context is the data set presented by Cucinotta et al, where the dose dependence of V79 cells is investigated by measuring with filter elution techniques the rejoining up to 3 hours after irradiation [54].…”

Section: Discussionsupporting

confidence: 58%

Induction and Processing of the Radiation-Induced Gamma-H2AX Signal and Its Link to the Underlying Pattern of DSB: A Combined Experimental and Modelling Study

et al. 2015

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We present here an analysis of DSB induction and processing after irradiation with X-rays in an extended dose range based on the use of the γH2AX assay. The study was performed by quantitative flow cytometry measurements, since the use of foci counting would result in reasonable accuracy only in a limited dose range of a few Gy. The experimental data are complemented by a theoretical analysis based on the GLOBLE model. In fact, original aim of the study was to test GLOBLE predictions against new experimental data, in order to contribute to the validation of the model. Specifically, the γH2AX signal kinetics has been investigated up to 24 h after exposure to increasing photon doses between 2 and 500 Gy. The prolonged persistence of the signal at high doses strongly suggests dose dependence in DSB processing after low LET irradiation. Importantly, in the framework of our modelling analysis, this is related to a gradually increased fraction of DSB clustering at the micrometre scale. The parallel study of γH2AX dose response curves shows the onset of a pronounced saturation in two cell lines at a dose of about 20 Gy. This dose is much lower than expected according to model predictions based on the values usually adopted for the DSB induction yield (≈ 30 DSB/Gy) and for the γH2AX foci extension of approximately 2 Mbp around the DSB. We show and discuss how theoretical predictions and experimental findings can be in principle reconciled by combining an increased DSB induction yield with the assumption of a larger genomic extension for the single phosphorylated regions. As an alternative approach, we also considered in our model the possibility of a 3D spreading-mechanism of the H2AX phosphorylation around the induced DSB, and applied it to the analysis of both the aspects considered. Our results are found to be supportive for the basic assumptions on which GLOBLE is built. Apart from giving new insights into the H2AX phosphorylation process, experiments performed at high doses are of relevance in the context of radiation therapy, where hypo-fractionated schemes become increasingly popular.

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Section: Discussionsupporting

confidence: 58%

Induction and Processing of the Radiation-Induced Gamma-H2AX Signal and Its Link to the Underlying Pattern of DSB: A Combined Experimental and Modelling Study

et al. 2015

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“…These include techniques such as alkaline or neutral filter elution [103,104], alkaline unwinding [105,106], sucrose gradient centrifugation [107][108][109] or pulsed field gel electrophoresis [110][111][112][113]. However the utility of such techniques for molecular epidemiological studies investigating low doses effects is limited as none can be used to investigate DNA damage after exposures to doses under 2 Gy and at the single cell level.…”

Section: Dna Single/double Strand Breaksmentioning

confidence: 99%

Ionizing radiation biomarkers for potential use in epidemiological studies

Pernot

Hall

Baatout

et al. 2012

Mutation Research/Reviews in Mutation Research

195

153

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Ionizing radiation is a known human carcinogen that can induce a variety of biological effects depending on the physical nature, duration, doses and dose-rates of exposure. However, the magnitude of health risks at low doses and dose-rates (below 100mSv and/or 0.1mSvmin(-1)) remains controversial due to a lack of direct human evidence. It is anticipated that significant insights will emerge from the integration of epidemiological and biological research, made possible by molecular epidemiology studies incorporating biomarkers and bioassays. A number of these have been used to investigate exposure, effects and susceptibility to ionizing radiation, albeit often at higher doses and dose rates, with each reflecting time-limited cellular or physiological alterations. This review summarises the multidisciplinary work undertaken in the framework of the European project DoReMi (Low Dose Research towards Multidisciplinary Integration) to identify the most appropriate biomarkers for use in population studies. In addition to logistical and ethical considerations for conducting large-scale epidemiological studies, we discuss the relevance of their use for assessing the effects of low dose ionizing radiation exposure at the cellular and physiological level. We also propose a temporal classification of biomarkers that may be relevant for molecular epidemiology studies which need to take into account the time elapsed since exposure. Finally, the integration of biology with epidemiology requires careful planning and enhanced discussions between the epidemiology, biology and dosimetry communities in order to determine the most important questions to be addressed in light of pragmatic considerations including the appropriate population to be investigated (occupationally, environmentally or medically exposed), and study design. The consideration of the logistics of biological sample collection, processing and storing and the choice of biomarker or bioassay, as well as awareness of potential confounding factors, are also essential.

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“…Repair may reach a plateau of residual, unrepaired and potentially also misrepaired, DSBs Dahm-Daphi and Dikomey 1996). Longer half-lives and more residual breaks have been observed in cells exposed to densely ionising particles.…”

Section: Pathways For Repairing Dna Double-strand Breaksmentioning

confidence: 99%

DNA Repair

Borgmann¹,

Köcher²,

Kriegs³

et al. 2016

Molecular Radio-Oncology

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Cellular chromosomal DNA is the principal target through which ionising radiation exerts it diverse biological effects. This chapter summarises the relevant DNA damage signalling and repair pathways used by normal and tumour cells in response to irradiation. Strategies for tumour radiosensitisation are reviewed which exploit tumour-specific DNA repair deficiencies or signalling pathway addictions, with a special focus on growth factor signalling, PARP, cancer stem cells, cell cycle checkpoints and DNA replication. This chapter concludes with a discussion of DNA repair-related candidate biomarkers of tumour response which are of crucial importance for implementing precision medicine in radiation oncology.

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Rejoining of DNA double-strand breaks in X-irradiated CHO cells studied by constant- and graded-field gel electrophoresis

Cited by 41 publications

References 27 publications

Induction and Processing of the Radiation-Induced Gamma-H2AX Signal and Its Link to the Underlying Pattern of DSB: A Combined Experimental and Modelling Study

Induction and Processing of the Radiation-Induced Gamma-H2AX Signal and Its Link to the Underlying Pattern of DSB: A Combined Experimental and Modelling Study

Ionizing radiation biomarkers for potential use in epidemiological studies

DNA Repair

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