Direct observation of damage clustering in irradiated DNA with atomic force microscopy

Xu, Xu; Nakano, Toshiaki; Tsuda, Masashi; Kanamoto, Ryota; Hirayama, Ryoichi; Uzawa, Akiko; Ide, Hiroshi

doi:10.1093/nar/gkz1159

Cited by 30 publications

(58 citation statements)

References 45 publications

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“…that the efficiency for detecting BD under atomic force microscopy (AFM) operation is over 90% which is consistent with the experimental efficiency [41]. Moreover, this agreement shown in Figure 1B suggests (i) that the density of ionizations and electronic excitation events clearly reflects the damage complexity, (ii) that inter-lesion distance in the AFM experiment is within approximately 10 bp and (iii) that 9 ionization and electronic excitation events are needed for inducing one additional BD at the DSB site.…”

Section: Comparison Between the Present Model And Experimental Complesupporting

confidence: 84%

“…Based on the comparison results shown in Figure 1, the simple methodology in the present DNA damage model is reasonable and sufficient for estimating complex BDs and for identifying the is the fractions of simple DSB, DSB/BD and DSB/BD/BD. The experimental data were obtained from the literature with treatment of base excision repair enzymes after 150 kVp X-ray irradiation [37,38] for (A) and with the direct observation technique with AFM after 70 kVp X-ray irradiation [41] for (B). The calculation represents the present model estimation based on Equations (2)-(5) and cluster analysis based on Table 1, and the determination of isolated or complex damage also follows the summary in Table 1.…”

Section: Comparison Between the Present Model And Experimental Complementioning

confidence: 99%

“…To directly compare our simulation results with experimental complex damage data [41], we considered the experimental detection efficiency η in our simulation. Focusing on the type of complex damage, as shown in Figure 1B, the present cluster analysis for identifying complex DSB types, in which the efficiency η = 0.9 was considered, also accurately reproduced the experimental results [41]. It should be noted that the yields of a BD and a cBD, Y BD and Y cBD , are proportional to the efficiency η and the square η 2 , respectively (e.g., Y BD × η and Y cBD × η 2 ).…”

Section: Comparison Between the Present Model And Experimental Complementioning

confidence: 99%

“…Meanwhile, complex DNA damage composed of BD can be quantified by means of gel electrophoresis after treatment of base excision repair enzymes [24,30,37,38] and fluorescence resonance energy transfer [39,40]. The structure of complex DNA damage, i.e., the number of lesions per damaged site was recently revealed with atomic force microscopy (AFM), where an individual BD in a complex damage site is specifically labelled with biotin/avidin coupled with an aldehyde reactive probe (ARP) [41]. However, whether all complex BD caused within a few bp can be detected in the AFM experiment [41] or not remains unknown.…”

Section: Introductionmentioning

confidence: 99%

“…The structure of complex DNA damage, i.e., the number of lesions per damaged site was recently revealed with atomic force microscopy (AFM), where an individual BD in a complex damage site is specifically labelled with biotin/avidin coupled with an aldehyde reactive probe (ARP) [41]. However, whether all complex BD caused within a few bp can be detected in the AFM experiment [41] or not remains unknown. Thus, it is essential to compare simulations based on track structure with the corresponding experimental data, which contributes to interpreting the detection efficiency of complex BD.…”

Section: Introductionmentioning

confidence: 99%

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A Simplified Cluster Analysis of Electron Track Structure for Estimating Complex DNA Damage Yields

Matsuya

Nakano

Kai

et al. 2020

IJMS

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Complex DNA damage, defined as at least two vicinal lesions within 10–20 base pairs (bp), induced after exposure to ionizing radiation, is recognized as fatal damage to human tissue. Due to the difficulty of directly measuring the aggregation of DNA damage at the nano-meter scale, many cluster analyses of inelastic interactions based on Monte Carlo simulation for radiation track structure in liquid water have been conducted to evaluate DNA damage. Meanwhile, the experimental technique to detect complex DNA damage has evolved in recent decades, so both approaches with simulation and experiment get used for investigating complex DNA damage. During this study, we propose a simplified cluster analysis of ionization and electronic excitation events within 10 bp based on track structure for estimating complex DNA damage yields for electron and X-ray irradiations. We then compare the computational results with the experimental complex DNA damage coupled with base damage (BD) measured by enzymatic cleavage and atomic force microscopy (AFM). The computational results agree well with experimental fractions of complex damage yields, i.e., single and double strand breaks (SSBs, DSBs) and complex BD, when the yield ratio of BD/SSB is assumed to be 1.3. Considering the comparison of complex DSB yields, i.e., DSB + BD and DSB + 2BD, between simulation and experimental data, we find that the aggregation degree of the events along electron tracks reflects the complexity of induced DNA damage, showing 43.5% of DSB induced after 70 kVp X-ray irradiation can be classified as a complex form coupled with BD. The present simulation enables us to quantify the type of complex damage which cannot be measured through in vitro experiments and helps us to interpret the experimental detection efficiency for complex BD measured by AFM. This simple model for estimating complex DNA damage yields contributes to the precise understanding of the DNA damage complexity induced after X-ray and electron irradiations.

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Section: Comparison Between the Present Model And Experimental Complesupporting

confidence: 84%

Section: Comparison Between the Present Model And Experimental Complementioning

confidence: 99%

Section: Comparison Between the Present Model And Experimental Complementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

A Simplified Cluster Analysis of Electron Track Structure for Estimating Complex DNA Damage Yields

Matsuya

Nakano

Kai

et al. 2020

IJMS

Self Cite

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Nanoscopic biodosimetry using plasmid DNA in radiotherapy with metallic nanoparticles

Mansouri

Mesbahi

Hejazi

et al. 2022

J Applied Clin Med Phys

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Nanoscopic lesions (complex damages), are the most lethal lesions for the cells. As nanoparticles have become increasingly popular in radiation therapy and the importance of analyzing nanoscopic dose enhancement has increased, a reliable tool for nanodosimetry has become indispensable. In this regard, the DNA plasmid is a widely used tool as a nanodosimetry probe in radiobiology and nano‐radiosensitization studies. This approach is helpful for unraveling the radiosensitization role of nanoparticles in terms of physical and physicochemical effects and for quantifying radiation‐induced biological damage. This review discusses the potential of using plasmid DNA assays for assessing the relative effects of nano‐radiosensitizers, which can provide a theoretical basis for the development of nanoscopic biodosimetry and nanoparticle‐based radiotherapy.

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Virus‐Inspired Hollow Mesoporous Gadolinium‐Bismuth Nanotheranostics for Magnetic Resonance Imaging‐Guided Synergistic Photodynamic‐Radiotherapy

Liu

Wang

Xie

et al. 2021

Adv Healthcare Materials

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The anti‐tumor efficacy of single photodynamic therapy (PDT) and radiotherapy (RT) has been greatly affected by inadequate tumor uptake of photo/radiation sensitizers, limited laser penetration depth, and radiation sickness caused by high doses of X‐rays. Here, the authors report a biomimetic coronavirus‐inspired hollow mesoporous gadolinium/bismuth nanocarrier loaded with a new NIR photosensitizer HB (termed as HB@VHMBi‐Gd) for magnetic resonance imaging (MRI)‐guided synergistic photodynamic‐RT. HB@VHMBi‐Gd displayed a faster cellular uptake rate than the conventional spherical HMBi‐Gd loaded with HB (HB@SHMBi‐Gd) because of rough surface‐enhanced adhesion. After intravenous injection, HB@VHMBi‐Gd is efficiently delivered to the tumor and rapidly invades the tumor cells by surface spikes. Interestingly, lysosomal acidity can trigger the degradation of VHMBi‐Gd to produce ultrasmall nanoparticles to amplify the X‐ray attenuation ability and enhance MRI contrast and radiosensitization. Under laser and X‐ray irradiation, HB@VHMBi‐Gd significantly enhances 1O2 generation from HB to induce activation of caspase 9/3 and inhibition of C‐myc, while enhancing hydroxyl radical generation from Bi2O3 to induce intense DNA breakage. By synergistically inducing cell apoptosis by distinct reactive oxygen species (ROS), HB@VHMBi‐Gd exhibits superior anticancer efficacy with ≈90% tumor inhibition. They envision that biomimetic virus‐inspired hollow hybrid metal nanoparticles can provide a promising strategy for imaging‐guided synergistic photodynamic‐RT.

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Direct observation of damage clustering in irradiated DNA with atomic force microscopy

Cited by 30 publications

References 45 publications

A Simplified Cluster Analysis of Electron Track Structure for Estimating Complex DNA Damage Yields

A Simplified Cluster Analysis of Electron Track Structure for Estimating Complex DNA Damage Yields

Nanoscopic biodosimetry using plasmid DNA in radiotherapy with metallic nanoparticles

Virus‐Inspired Hollow Mesoporous Gadolinium‐Bismuth Nanotheranostics for Magnetic Resonance Imaging‐Guided Synergistic Photodynamic‐Radiotherapy

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