EPI-CT: in vitro assessment of the applicability of the γ-H2AX-foci assay as cellular biomarker for exposure in a multicentre study of children in diagnostic radiology

Vandevoorde, Charlot; Gomolka, Maria; Roessler, Ute; Samaga, Daniel; Lindholm, Carita; Fernet, Marie; Hall, Janet; Pernot, Eileen; El‐Saghire, Houssein; Baatout, Sarah; Kesminiene, Ausrele; Thierens, Hubert

doi:10.3109/09553002.2015.1047987

Cited by 29 publications

(25 citation statements)

References 44 publications

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“…One of the main events in the DSB repair is phosphorylation of H2AX, the variant of histone family 2A, that serves as a chromatin scaffold within a 2-Mb DNA domain recruiting the proteins involved in DSB repair [2]. The γH2AX protein has become a well-established biomarker for IRIF in low-dose research [3], diagnostic radiology [4][5][6], cancer research and therapy [7,8], and biological dosimetry [9][10][11]. Along with discrete foci, immunostaining with antibodies against γH2AX reveals so-called γH2AX pan-staining, which represents a visual manifestation of cells in early apoptosis [12].…”

Section: Introductionmentioning

confidence: 99%

“…While the γH2AX and 53BP1 are commonly accepted molecular markers for biological dosimetry and enumeration of DSB, they do not always co-localize with DSB due to different kinetics of γH2AX dephosphorylation and relocalization of 53BP1 from the location of the DSB [18,19]. Although co-localization of γH2AX/53BP1 is currently considered as the most reliable marker of the DSB, more research is needed to define limitations of γH2AX and 53BP1 assays for the DSB quantification [6]. In this study, we provide further evidence that both γH2AX and 53BP1 foci persist in cells a longer time than needed for the DSB repair.…”

Section: Introductionmentioning

confidence: 99%

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Biodosimetry of Low Dose Ionizing Radiation Using DNA Repair Foci in Human Lymphocytes

Jakl

Markovà

Kolariková

et al. 2020

Genes

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Purpose: Ionizing radiation induced foci (IRIF) known also as DNA repair foci represent most sensitive endpoint for assessing DNA double strand breaks (DSB). IRIF are usually visualized and enumerated with the aid of fluorescence microscopy using antibodies to γH2AX and 53BP1. This study analyzed effect of low dose ionizing radiation on residual IRIF in human lymphocytes to the aim of potential biodosimetry and possible extrapolation of high-dose γH2AX/53BP1 effects to low doses and compared kinetics of DSB and IRIF. We also analyzed whether DNaseI, which is used for reducing of clumps, affects the IRIF level. Materials and Methods: The cryopreserved human lymphocytes from umbilical cord blood (UCB) were thawed with/without DNaseI, γ-irradiated at doses of 0, 5, 10, and 50 cGy and γH2AX/53BP1 foci were analyzed 30 min, 2 h, and 22 h post-irradiation using appropriate antibodies. We also analyzed kinetics of DSB using PFGE. Results: No significant difference was observed between data obtained by γH2AX foci evaluation in cells that were irradiated by low doses and data obtained by extrapolation from higher doses. Residual 53BP1 foci induced by low doses significantly outreached the data extrapolated from irradiation by higher doses. 53BP1 foci induced by low dose-radiation remain longer at DSB loci than foci induced by higher doses. There was no significant effect of DNaseI on DNA repair foci. Conclusions: Primary γH2AX, 53BP1 foci and their co-localization represent valuable markers for biodosimetry of low doses, but their usefulness is limited by short time window. Residual γH2AX and 53BP1 foci are more useful markers for biodosimetry in vitro. Effects of low doses can be extrapolated from high dose using γH2AX residual foci while γH2AX/53BP1 foci are valuable markers for evaluation of initial DSB induced by ionizing radiation. Residual IRIF induced by low doses persist longer time than those induced by higher doses.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Biodosimetry of Low Dose Ionizing Radiation Using DNA Repair Foci in Human Lymphocytes

Jakl

Markovà

Kolariková

et al. 2020

Genes

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“…The formation and persistence of γH2AX with time after radiation exposure has the potential to be a sensitive biomarker of exposure. Indeed foci can be detected after radiation exposure to low doses (10 mGy) such as those received after a CT scan [52,87,88]. However, detailed evaluation of γH2AX as a biomarker of low dose exposure has revealed substantial difficulties, which are discussed below.…”

Section: γH2ax and Dna Repair Focimentioning

confidence: 99%

“…The choice of tissues will also depend on the purpose of the study and what is feasible and ethical to collect from the study population. The method of blood collection and treatment of samples, as well as the factors discussed above relating to technique and protocols, impact on γH2AX quantification and can explain part of the variation seen between laboratories in γH2AX measurements [88,90,91]…”

Section: Assay Design and Validationmentioning

confidence: 99%

“…For example the induction of γ-H2AX at 0.5 h after ex vivo blood irradiation, and peak formation at 2 h were independent of age, gender and ethnicity but varied with race and alcohol use, which delayed the peak to 4 h [94]. [34,96,97] and one in the low dose range [88] have been performed using blood samples irradiated ex vivo to assess this endpoint for biodosimetry purposes. Compared to other endpoints (dicentrics, micronuclei, gene expression), the γH2AX assay was the most rapid, providing results within 24 h. However, it showed considerable variability at both high and low doses (0.1 to -6.4 Gy),…”

Section: Intra-and Inter-individual Variation In Responsementioning

confidence: 99%

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Ionizing radiation biomarkers in epidemiological studies – An update

Hall

Jeggo

West

et al. 2017

Mutation Research/Reviews in Mutation Research

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105

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Recent epidemiology studies highlighted the detrimental health effects of exposure to low dose and low dose rate ionizing radiation (IR): nuclear industry workers studies have shown increased leukaemia and solid tumour risks following cumulative doses of <100mSv and dose rates of <10mGy per year; paediatric patients studies have reported increased leukaemia and brain tumours risks after doses of 30-60mGy from computed tomography scans. Questions arise, however, about the impact of even lower doses and dose rates where classical epidemiological studies have limited power but where subsets within the large cohorts are expected to have an increased risk. Further progress requires integration of biomarkers or bioassays of individual exposure, effects and susceptibility to IR. The European DoReMi (Low Dose Research towards Multidisciplinary Integration) consortium previously reviewed biomarkers for potential use in IR epidemiological studies. Given the increased mechanistic understanding of responses to low dose radiation the current review provides an update covering technical advances and recent studies. A key issue identified is deciding which biomarkers to progress. A roadmap is provided for biomarker development from discovery to implementation and used to summarise the current status of proposed biomarkers for epidemiological studies. Most potential biomarkers remain at the discovery stage and for some there is sufficient evidence that further development is not warranted. One biomarker identified in the final stages of development and as a priority for further research is radiation specific mRNA transcript profiles.

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Biomarkers of mitochondrial stress and DNA damage during pediatric catheter-directed neuroangiography – a prospective single-center study

Hogarth,

Shkumat,

Goman

et al. 2024

Pediatr Radiol

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EPI-CT: in vitro assessment of the applicability of the γ-H2AX-foci assay as cellular biomarker for exposure in a multicentre study of children in diagnostic radiology

Abstract: The results demonstrate that it is feasible to apply the γ-H2AX foci assay as a cellular biomarker of exposure in a multicentre prospective study in paediatric CT imaging after validating it in an in vivo international pilot study on paediatric patients.

Cited by 29 publications

References 44 publications

Biodosimetry of Low Dose Ionizing Radiation Using DNA Repair Foci in Human Lymphocytes

Biodosimetry of Low Dose Ionizing Radiation Using DNA Repair Foci in Human Lymphocytes

Ionizing radiation biomarkers in epidemiological studies – An update

Biomarkers of mitochondrial stress and DNA damage during pediatric catheter-directed neuroangiography – a prospective single-center study

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