γ-H2AX Foci as a Biomarker for Patient X-Ray Exposure in Pediatric Cardiac Catheterization

Beels, Laurence; Bacher, Klaus; Wolf, Daniël De; Werbrouck, Joke; Thierens, Hubert

doi:10.1161/circulationaha.109.880385

Cited by 160 publications

(119 citation statements)

References 40 publications

(51 reference statements)

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“…An increase in DSB was likewise shown after cardiac catheterization in children; the induced γ-H2AX foci in the low-dose range up to 5 mGy, however, correlated non-linearly with the blood dose determined using Monte Carlo simulation. In this instance the authors, similarly to the CT studies above, presume hypersensitivity in the low-dose range [24]. Two other studies demonstrated that the repair kinetics of DSB should be taken into account, especially due to fractionated radiation exposure during intervention, otherwise a repair-related underestimate of the actual radiation damage will result.…”

Section: Dsb After Angiographymentioning

confidence: 88%

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Radiation Induced DNA Double-Strand Breaks in Radiology

Kuefner

Brand

Engert

et al. 2015

Fortschr Röntgenstr

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Background !Shortly after the discovery of X-ray radiation, its detrimental effect on biological tissue was observed. The increasing number of X-raybased examinations in recent decades has reAbstract ! Shortly after the discovery of X-rays, their damaging effect on biological tissues was observed. The determination of radiation exposure in diagnostic and interventional radiology is usually based on physical measurements or mathematical algorithms with standardized dose simulations. γ-H2AX immunofluorescence microscopy is a reliable and sensitive method for the quantification of radiation induced DNA double-strand breaks (DSB) in blood lymphocytes. The detectable amount of these DNA damages correlates well with the dose received. However, the biological radiation damage depends not only on dose but also on other individual factors like radiation sensitivity and DNA repair capacity. Iodinated contrast agents can enhance the x-ray induced DNA damage level. After their induction DSB are quickly repaired. A protective effect of antioxidants has been postulated in experimental studies. This review explains the prinicple of the γ-H2AX technique and provides an overview on studies evaluating DSB in radiologic examinations. Key Points:▶ Radiologic examinations including CT and angiography induce DNA double-strand breaks. Even after mammography a slight but significant increase is detectable in peripheral blood lymphocytes.▶ The number of radiation induced doublestrand breaks correlates well with the radiation dose.▶ Individual factors including radiation sensitivity, DNA repair capacity and the application of iodinated contrast media has an influence on the DNA damage level. This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.sulted in the heightened importance of radiation dosage and protection as clinical topics [1, 2]. Determination of dose exposure in diagnostic and interventional radiology is carried out primarily using physical methods based on standardized phantoms or relying on mathematical dosage simulations. Such estimates can determine the exposure quite well, but supply no information regarding the interaction of radiation in the patient's body. Nowadays there are indications that biological radiation damage is not solely dependent on the applied dosage, but is also related to additional individual factors that cannot be sufficiently determined using established dosimetric methods. Earlier approaches to biological dosimetry were not sensitive enough for the dosage range used in radiology [3]. Double-stand breaks (DSB) are considered the most relevant radiation-induced damage to deoxyribonucleic acid (DNA) [4]. Although such breakage is quickly repaired, defective repairs can result in mutations, causing carcinogenesis [5, 6]. An immunofluorescence microscopic approach, which is much more sensitive than previous biological processes, allows the determination of individual DNA DSB in peripheral blood lymphocytes, thus allowing an accurate estimation of the biolog...

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Section: Dsb After Angiographymentioning

confidence: 88%

“…This quantity of radiation-induced foci demonstrate a dependence on the dose, which in most in-vitro and in-vivo studies was linear [7, 9,13,23,33]. Individual studies described non-linear relationships [14,15,24]. However, it should be noted that in this working group, the baseline values were higher by a factor of 10 ( • " Table 1).…”

mentioning

confidence: 86%

Radiation Induced DNA Double-Strand Breaks in Radiology

Kuefner

Brand

Engert

et al. 2015

Fortschr Röntgenstr

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“…For example, gH2AX focus quantification has been used to assess the risk of exposure to ionizing radiation during clinical computed tomographic scans (59)(60)(61)(62) and to estimate the dose during radiotherapy (63)(64)(65) or in case of radiation accidents (66). Infrastructures for high-throughput biodensitometry screening after a radiologic event have been developed based on the gH2AX assay (67), and the European Biodosimetry Network is conducting large studies to evaluate the use of gH2AX focus quantification as a risk assessment tool in such cases (68).…”

Section: Reevaluation Of the Most Commonly Used Dsb Markermentioning

confidence: 99%

Superresolution light microscopy shows nanostructure of carbon ion radiation‐induced DNA double‐strand break repair foci

et al. 2016

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Carbon ion radiation is a promising new form of radiotherapy for cancer, but the central question about the biologic effects of charged particle radiation is yet incompletely understood. Key to this question is the understanding of the interaction of ions with DNA in the cell's nucleus. Induction and repair of DNA lesions including double-strand breaks (DSBs) are decisive for the cell. Several DSB repair markers have been used to investigate these processes microscopically, but the limited resolution of conventional microscopy is insufficient to provide structural insights. We have applied superresolution microscopy to overcome these limitations and analyze the fine structure of DSB repair foci. We found that the conventionally detected foci of the widely used DSB marker gH2AX (Ø 700-1000 nm) were composed of elongated subfoci with a size of ∼100 nm consisting of even smaller subfocus elements (Ø 40-60 nm). The structural organization of the subfoci suggests that they could represent the local chromatin structure of elementary DSB repair units at the DSB damage sites. Subfocus clusters may indicate induction of densely spaced DSBs, which are thought to be associated with the high biologic effectiveness of carbon ions. Superresolution microscopy might emerge as a powerful tool to improve our knowledge of interactions of ionizing radiation with

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“…Gamma-H2AX foci analysis was used as a biomarker for individual radiation damage in pediatric patients undergoing cardiac catherization showing that previous estimates according to linear-no-treshold hypothesis have been underestimating radiation damage. Therefore, gamma-H2AX foci analysis could be used as a tool for estimations of DNA-damage effects after cardiac catherization (Beels, Bacher et al 2009). Another study showed that the amount of gamma-H2AX foci in lymphocytes after coronary CT angiography correlates to dose-length product (DLP) which is a physical parameter used to calculate delivered dose after CT.…”

Section: Wwwintechopencommentioning

confidence: 99%