Simulation of Proton-Induced DNA Damage Patterns Using an Improved Clustering Algorithm

Tang, Jing; Xiao, Qinfeng; Gui, Zhiguo; Li, Baosheng; Zhang, Pengcheng

doi:10.1667/rr15552.1

Cited by 3 publications

(5 citation statements)

References 57 publications

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“…First, the number of SSBs from the proton irradiation is lower than that from the electron, while the number of DSBs is higher. It is consistent with the damage behavior as a function of LET obtained with the G0/G1 DNA model by others (Tang et al 2020). Second, both SSBs and DSBs from protons are associated with much larger error bars than from electron and Co-60 irradiations.…”

Section: Dna Damage Studysupporting

confidence: 90%

“…In figure 6(a) and (b), we also show the mean and standard deviation of DNA damage from the Co-60 (grey dashed line), electron (red dashed line) and proton (blue dashed line) irradiations on the G0/G1 DNA geometry. Like the metaphase DNA situation, SSBs decrease and DSBs increase along with the increase of the LET (Co-60 and electron to proton), consistent with the previous publications (Tang et al 2020). Meanwhile, a larger fluctuation is also observed for the proton than for the Co-60 and electron irradiations.…”

Section: Dna Damage Studysupporting

confidence: 90%

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Development and implementation of a metaphase DNA model for ionizing radiation induced DNA damage calculation

Sitmukhambetov¹,

Dinh²,

Lai³

et al. 2022

Phys. Med. Biol.

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Objective: To develop a metaphase chromosome model representing the complete genome of a human lymphocyte cell to support microscopic Monte Carlo (MMC) simulation-based radiation-induced DNA damage studies. Approach: We employed coarse-grained polymer physics simulation to obtain a rod-shaped chromatid segment to match Hi-C data. We voxelized the segment and connected the chromatid with pre-constructed nucleosomes and linker DNAs in base-pair (bp) resolutions. We then piled different numbers of voxelized chromatid segments to create the chromosomes. Finally, we arranged the chromosomes at the cell metaphase plate to create the complete set of metaphase chromosomes. We implemented the model in gMicroMC simulation by denoting the DNA structure in a four-level hierarchical tree: nucleotide pairs, nucleosomes and linker DNAs, chromatid segments, and chromosomes. We applied the model to compute DNA damage under different radiation conditions and compared the results to those obtained with G0/G1 model and experimental measurements. We also performed uncertainty analysis for relevant simulation parameters. Main Results: The chromatid segment was successfully voxelized and connected in base-pair (bps) resolution. With 466 segments, we obtained the metaphase chromosome containing 12.5 Gbps of DNA. Applying it to compute radiation-induced DNA damage, the obtained results were self-consistent and agreed with experimental measurements. Through parameter uncertainty study, we found the DNA damage ratio between metaphase and G0/G1 phase was not sensitive to the chemical simulation time. The damage was also not sensitive to the specific parameter settings in the polymer physics simulation, as long as the produced metaphase model followed a similar contact probability. Significance: Experimental data reveal that ionizing radiation induced DNA damage is cell-cycle dependent. Yet, DNA chromosome models, except for G0/G1 phase, are not available in the state-of-the-art MMC simulation. For the first time, we successfully built a metaphase chromosome model and implemented it into MMC simulation for radiation-induced DNA damage computation.

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Section: Dna Damage Studysupporting

confidence: 90%

Section: Dna Damage Studysupporting

confidence: 90%

Development and implementation of a metaphase DNA model for ionizing radiation induced DNA damage calculation

Sitmukhambetov¹,

Dinh²,

Lai³

et al. 2022

Phys. Med. Biol.

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“…The Geant4-DNA platform has since been applied in many studies of damage to the DNA molecule and its higher-order structures in mammalian cells (Figs. 9.17 and 9.18) and other organisms exposed to many radiation types, including those of interest in radiotherapy, space travel, and radiobiology (Chatzipapas et al , 2020; 2021; 2023; Dominguez-Kondo et al , 2021; Dos Santos et al , 2020; Henthorn et al , 2017; Hilgers et al , 2022; Incerti et al , 2016; 2020; Kyriakou et al , 2021; 2022; Lee and Wang, 2019; Margis et al , 2020; Moeini et al , 2020; Mokari et al , 2020; Sakata et al , 2019; Tang et al , 2020; Thibault et al , 2022; Thompson et al , 2022). Development of the Geant4-DNA platform for radiobiological applications included incorporation of a feature allowing for prediction of DNA rejoining kinetics and corresponding cell surviving fraction as a function of time.…”

Section: Applications Of Stochastic Characteristics Of Radiation Inte...mentioning

confidence: 99%

“…DSB = double-strand break; LET = linear energy transfer. Journal of the ICRU 23(1)1-165 2020; Sakata et al, 2019;Tang et al, 2020;Thibault et al, 2022;Thompson et al, 2022). Development of the Geant4-DNA platform for radiobiological applications included incorporation of a feature allowing for prediction of DNA rejoining kinetics and corresponding cell surviving fraction as a function of time.…”

Section: Track Structure For Simulation Of Consequent Biological Damagementioning

confidence: 99%

ICRU Report 98, Stochastic Nature of Radiation Interactions: Microdosimetry

Braby,

Conte,

Dingfelder

et al. 2023

J�ICRU

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The Journal of the ICRU publishes reports on important and topical subjects within the field of radiation science and measurement. It is the successor to the series of reports published by or on behalf of the International Commission on Radiation Units and Measurements (ICRU) since 1927. The Commission continually reviews radiation science with the aim of identifying areas where the development of guidance and recommendations can make an important contribution.

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“…In proton microdosimetry study, Tang et al (2020) constructed a simple ellipsoid geometric model as the nucleus, and the density-based spatial clustering of applications with noise (DBSCAN) was adopted to analyze the cellular energy deposition induced by the front of the proton track to predict the yield of DNA double-strand breaks (DSBs) and single-strand breaks (SSBs). In another study, Matsuya et al (2022) utilized the Monte Carlo software PHITS to obtain the complete track of a monoenergetic proton and calculated the DNA damage caused by the entire proton tracks.…”

Section: Introductionmentioning

confidence: 99%

Microdosimetric assessment about proton spread-out Bragg peak at different depths based on the normal human mesh-type cell population model

et al. 2023

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Objective. In clinical proton therapy, the spread-out Bragg peak (SOBP) is commonly used to fit the target shape. Dose depositions at microscopic sites vary, even with a consistent absorbed dose ( D ) in SOBP. In the present study, monolayer mesh-type cell population models were developed for microdosimetric assessment at different SOBP depths. Approach. Normal human bronchial epithelial (BEAS-2B) and hepatocytes (L-O2) mesh-type cell models were constructed based on fluorescence tomography images of normal human cells. Particle transport simulation in cell populations was performed coupled with Monte Carlo software PHITS. The relationship between microdosimetry and macrodosimetry of SOBP at different depths was described by analyzing the microdosimetric indicators such as specific energy z , specific energy distribution f z , D , and relative standard deviation σ z / z ¯ within cells. Additionally, the microdosimetric distributions characteristics and their contributing factors were also discussed. Main results. The microscopic dose distribution is strongly influenced by cellular size, shape, and material. The mean specific energy z ¯ of nucleus and cytoplasm in the cell population is greater than the overall absorbed dose of the cell population model ( D p ), with a maximum z ¯ / D p of 1.1. The cellular dose distribution is different between the BEAS-2B mesh-type model and its concentric ellipsoid geometry-type model, which difference in z ¯ is about 10.3% for the nucleus and about 7.5% for the cytoplasm with the SOBP depth of 15 cm. When D = 2 Gy, the maximum z of L-O2 nucleus reaches 2.8 Gy and σ z / z ¯ is 5.1% at the mid-depth SOBP (16–18 cm); while the maximum z of the BEAS-2B nucleus reaches 2.2 Gy with only 2.7% of σ z / z ¯ . Significance. The significant variation of microdosimetric distributions of SOBP different depths indicates the necessity to use mesh-type cell population models, which have the potential to be compared with biological results and build the bio-physical model.

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Simulation of Proton-Induced DNA Damage Patterns Using an Improved Clustering Algorithm

Cited by 3 publications

References 57 publications

Development and implementation of a metaphase DNA model for ionizing radiation induced DNA damage calculation

Development and implementation of a metaphase DNA model for ionizing radiation induced DNA damage calculation

ICRU Report 98, Stochastic Nature of Radiation Interactions: Microdosimetry

Microdosimetric assessment about proton spread-out Bragg peak at different depths based on the normal human mesh-type cell population model

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