DNA damage induction during localized chronic exposure to an insoluble radioactive microparticle

Matsuya, Yusuke; Satou, Yukihiko; Hamada, Nobuyuki; Date, Hiroyuki; Ishikawa, Masayori; Sato, Tatsuhiko

doi:10.1038/s41598-019-46874-6

Cited by 12 publications

(25 citation statements)

References 52 publications

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“…Experimental methods for detecting complex DNA damage have evolved in recent decades [24,[30][31][32][33][34][35][36]. Among several techniques [24,[30][31][32][33][34][35][36], microscopic operations coupled with an antibody against γ-H2AX [31][32][33][34] enables researchers to obtain spatial distributions of DSB induction in the cell nucleus. The adjacent degree of the DSB site can be evaluated from γ-H2AX foci volume in an assay [35,36]; however, the damage complexity at the nano-meter scale (the scale of DNA) cannot be obtained due to the limited spatial resolution from hundreds of nm to a few µm [35,36].…”

Section: Introductionmentioning

confidence: 99%

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: Introductionmentioning

confidence: 99%

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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“…Considering that a Cs-BMP can adhere to lung tissue, we used two types of normal human diploid lung cell lines: WI-38 primary lung fibroblasts (RCB0702, RIKEN, Tokyo, Japan) and HBEC3-KT bronchial epithelial cells immortalized with hTERT and CDK4 (CRL-4051, ATCC, Manassas, VA, USA). WI-38 cells were maintained in Dulbecco’s modified Eagle’s medium/Nutrient Mixture F-12 (DMEM/F12) (D8437, Sigma, Kawasaki, Japan) supplemented with 10% fetal bovine serum (FBS, Nichirei Bioscience Inc., Tokyo, Japan), and the HBEC3-KT cells were maintained in bronchial epithelial cell medium (3211NZ, ScienCell, Carlsbad, CA, USA), as described in [ 8 ]. WI-38 and HBEC3-KT cells were maintained at 37 °C in a humidified atmosphere of 5% CO 2 in air.…”

Section: Methodsmentioning

confidence: 99%

“…Meanwhile, Cs-BMPs are assumed to adhere in the long term to normal tissues due to their insoluble nature. Considering local energy deposition around a Cs-BMP [ 8 ], normal tissues are assumed to be chronically and partially exposed at a microenvironmental scale. However, such heterogeneous dose distribution within the tissue has not been considered in evaluating the radiation risk of Cs-BMPs.…”

Section: Introductionmentioning

confidence: 99%

“…There are several reports on responses of human normal cells to local radiation exposure [ 8 , 11 , 12 ]. Among them, our previous in vitro study reported on the spatial distribution of DNA double-strand breaks (DSBs), which was detected by the histone H2AX phosphorylated on serine 139 (γ-H2AX foci) at DSB sites [ 13 , 14 ], after 24 h exposure to Cs-BMP with 505.7 Bq [ 8 ]. Our previous results suggest that local exposure to a Cs-BMP leads to an increase in DNA damage to distal cells and a decrease in DNA damage to proximal cells.…”

Section: Introductionmentioning

confidence: 99%

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Inflammatory Signaling and DNA Damage Responses after Local Exposure to an Insoluble Radioactive Microparticle

Matsuya

Hamada

Yachi

et al. 2022

Cancers

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Cesium-bearing microparticles (Cs-BMPs) can reach the human respiratory system after inhalation, resulting in chronic local internal exposure. We previously investigated the spatial distribution of DNA damage induced in areas around a Cs-BMP; however, the biological impacts have not been fully clarified due to the limited amount of data. Here, we investigated the inflammatory signaling and DNA damage responses after local exposure to a Cs-BMP in vitro. We used two normal human lung cell lines, i.e., lung fibroblast cells (WI-38) and bronchial epithelial cells (HBEC3-KT). After 24 h exposure to a Cs-BMP, inflammation was evaluated by immunofluorescent staining for nuclear factor κB (NF-κB) p65 and cyclooxygenase 2 (COX-2). The number of DNA double-strand breaks (DSBs) was also detected by means of phospholylated histone H2AX (γ-H2AX) focus formation assay. Cs-BMP exposure significantly increased NF-κB p65 and COX-2 expressions, which were related to the number of γ-H2AX foci in the cell nuclei. Compared to the uniform (external) exposure to 137Cs γ-rays, NF-κB tended to be more activated in the cells proximal to the Cs-BMP, while both NF-κB p65 and COX-2 were significantly activated in the distal cells. Experiments with chemical inhibitors for NF-κB p65 and COX-2 suggested the involvement of such inflammatory responses both in the reduced radiosensitivity of the cells proximal to Cs-BMP and the enhanced radiosensitivity of the cells distal from Cs-BMP. The data show that local exposure to Cs-BMP leads to biological effects modified by the NF-κB pathway, suggesting that the radiation risk for Cs-BMP exposure can differ from that estimated based on conventional uniform exposure to normal tissues.

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“…In an in vitro study using Cs-bearing particles composed of 92.4% 137 Cs with 469.2 Bq and 7.6% 134 Cs with 38.5 Bq, Matsuya et al calculated by Monte Carlo code of PHITS (particle and heavy ion transport code system) the absorbed dose rates around the Cs-bearing particle 6 . They showed that the absorbed dose rate gradually decreased depending on the distance from the Cs-bearing particle, and there was a low absorbed dose rate of below 0.902 mGy/day at 1.65 mm from the particle.…”

Section: Introductionmentioning

confidence: 99%

Field size effects on DNA damage and proliferation in normal human cell populations irradiated with X-ray microbeams

Ojima

Ito

Usami

et al. 2021

Sci Rep

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To clarify the health risks of internal radiation exposure, it is important to investigate the radiological effects of local exposure at cell levels from radioactive materials taken up by organs. Focusing on the response of cell populations post-irradiation, X-ray microbeams are very effective at reproducing the effects of local exposure within an internal exposure in vitro. The present study aims to clarify the effects of local exposure by investigating the response of normal human cell (MRC-5) populations irradiated with X-ray microbeams of different beam sizes to DNA damage. The populations of MRC-5 were locally irradiated with X-ray microbeams of 1 Gy at 0.02–1.89 mm2 field sizes, and analyzed whether the number of 53BP1 foci as DSB (DNA double strand break) per cell changed with the field size. We found that even at the same dose, the number of DSB per cell increased depending on the X-irradiated field size on the cell population. This result indicated that DNA damage repair of X-irradiated cells might be enhanced in small size fields surrounded by non-irradiated cells. This study suggests that X-irradiated cells received some signal (a rescue signal) from surrounding non-irradiated cells may be involved in the response of cell populations post-irradiation.

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DNA damage induction during localized chronic exposure to an insoluble radioactive microparticle

Cited by 12 publications

References 52 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

Inflammatory Signaling and DNA Damage Responses after Local Exposure to an Insoluble Radioactive Microparticle

Field size effects on DNA damage and proliferation in normal human cell populations irradiated with X-ray microbeams

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