Clustered DNA damage on subcellular level: effect of scavengers

Brabcová, Kateřina Pachnerová; Sihver, Lembit; Yasuda, N.; Matuo, Youichirou; Štěpán, Václav; Davídková, Marie

doi:10.1007/s00411-014-0557-2

Cited by 13 publications

(5 citation statements)

References 32 publications

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“…When the LET of the particle increases, clusters contain an increasing number of modifications (Tsao et al, 2007 ; Pachnerova Brabcova et al, 2014 ). We exemplify this phenomenon in Figure 4 .…”

Section: Formation Of Dna Damages: Mechanistic Aspectsmentioning

confidence: 99%

Stress-induced DNA damage biomarkers: applications and limitations

et al. 2015

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A variety of environmental stresses like chemicals, UV and ionizing radiation and organism's endogenous processes such as replication stress and metabolism can lead to the generation of reactive oxygen and nitrogen species (ROS/RNS) that can attack cellular vital components like DNA, proteins and lipid membranes. Among them, much attention has been focused on DNA since DNA damage plays a role in several biological disorders and aging processes. Thus, DNA damage can be used as a biomarker in a reliable and accurate way to quantify for example radiation exposure and can indicate its possible long term effects and cancer risk. Based on the type of DNA lesions detected one can hypothesize on the most probable mechanisms involved in the formation of these lesions for example in the case of UV and ionizing radiation (e.g., X- or α-, γ-rays, energetic ions, neutrons). In this review we describe the most accepted chemical pathways for DNA damage induction and the different types of DNA lesions, i.e., single, complex DNA lesions etc. that can be used as DNA damage biomarkers. We critically compare DNA damage detection methods and their limitations. In addition, we suggest the use of DNA repair gene products as biomarkes for identification of different types of stresses i.e., radiation, oxidative, or replication stress, based on bioinformatic approaches and meta-analysis of literature data.

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Section: Formation Of Dna Damages: Mechanistic Aspectsmentioning

confidence: 99%

Stress-induced DNA damage biomarkers: applications and limitations

et al. 2015

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“…Clustered DNA damage involves multiple types of lesions in a small space, and the lesion ends of adjacent damage sites can recombine, increasing the potential for DNA mutations and chromosomal mutations and even induce severe cell apoptosis (Asaithamby et al, ; Gray et al, ; Hada & Georgakilas, ; Pachnerova Brabcova et al, ). Studies of the response to this complex damage are useful for developing methods to increase tumor cell apoptosis to improve the effect of heavy ion therapy.…”

Section: Introductionmentioning

confidence: 99%

Dynamic recognition and repair of DNA complex damage

Yan

Xie

Zhang

et al. 2018

Journal Cellular Physiology

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Irradiation (IR) can be used to treat cancer by inducing complex and irreparable DNA damage in the cancer cells, which may lead to their apoptotic death. However, little is known about the molecular mechanism of this DNA damage. Here, the non‐small‐cell lung cancer cell line A549 was treated with either X‐ray or carbon ion combined with bleomycin (BLM). The cell survival rate, frequency of double‐strand breaks (DSBs), dynamic changes in γH2AX, and p53 binding protein 1 (53BP1), and protein expression of Ku70, Rad51, and XRCC1 were determined by the clone formation assay, agarose gel electrophoresis, immunofluorescence, and western blot analysis. The results showed that the most obvious complex DSBs occurred in the carbon IR + BLM group. The number of γH2AX and 53BP1 foci in the 0.5 hr X‐ray IR + BLM group was the highest (p < 0.001) among all the groups. γH2AX foci were detected in the nucleus at 0.5, 1, 2, and 4 hr, but were distributed throughout the cell at 6 hr after IR in the carbon ion IR + BLM group. The expression of Ku70 increased and XRCC1 decreased at 2 and 6 hr after IR. Our data indicate that a DNA damage frequency of 13.4/Mbp is caused by clustered DNA damage and further show a correlation between γH2AX, 53BP1, and XRCC1 levels and the extent of DNA damage. The results of this study provide insights into DNA damage recognition and a rationale for the clinical use of radiotherapy.

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“…24,25 Hence, for the stabilization of DNA it is often suspended in ethylenediaminetetraacetic acid (EDTA) solution 6 or in a TE-buffer consisting of 2-amino-2-(hydroxymethyl)-1,3-propanediol (TRIS) and EDTA. 26,27 The sample is later lyophilized or used in the liquid phase, depending on the type of irradiation studies. After irradiation, the DNA samples are commonly analyzed by gel electrophoresis and compared to a nonirradiated sample.…”

mentioning

confidence: 99%

Hydroperoxyl radical and formic acid formation from common DNA stabilizers upon low energy electron attachment

Ribar

Huber

Śmiałek

et al. 2018

Phys. Chem. Chem. Phys.

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2-Amino-2-(hydroxymethyl)-1,3-propanediol (TRIS) and ethylenediaminetetraacetic acid (EDTA) are key components of biological buffers and are frequently used as DNA stabilizers in irradiation studies. Such surface or liquid phase studies are done with the aim to understand the fundamental mechanisms of DNA radiation damage and to improve cancer radiotherapy. When ionizing radiation is used, abundant secondary electrons are formed during the irradiation process, which are able to attach to the molecular compounds present on the surface. In the present study we experimentally investigate low energy electron attachment to TRIS and methyliminodiacetic acid (MIDA), an analogue of EDTA, supported by quantum chemical calculations. The most prominent dissociation channel for TRIS is through hydroperoxyl radical formation, whereas the dissociation of MIDA results in the formation of formic and acetic acid. These compounds are well-known to cause DNA modifications, like strand breaks. The present results indicate that buffer compounds may not have an exclusive protecting effect on DNA as suggested previously.

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Clustered DNA damage on subcellular level: effect of scavengers

Cited by 13 publications

References 32 publications

Stress-induced DNA damage biomarkers: applications and limitations

Stress-induced DNA damage biomarkers: applications and limitations

Dynamic recognition and repair of DNA complex damage

Hydroperoxyl radical and formic acid formation from common DNA stabilizers upon low energy electron attachment

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