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Integrated Modelling of Cell Responses after Irradiation for DNA-Targeted Effects and Non-Targeted Effects.

ABSTRACT: Intercellular communication after ionizing radiation exposure, so-called non-targeted effects (NTEs), reduces cell survival. Here we describe an integrated cell-killing model considering NTEs and DNA damage along radiation particle tracks, known as DNA-targeted effects (TEs) based on repair kinetics of DNA damage. The proposed model was applied to a series of experimental data, i.e., signal concentration, DNA damage kinetics, cell survival curve and medium transfer bystander effects (MTBEs). To reproduce the experimental data, the model considers the following assumptions: (i) the linear-quadratic (LQ) function as absorbed dose to express the hit probability to emit cell-killing signals, (ii) the potentially repair of DNA lesions induced by NTEs, and (iii) lower efficiency of repair for the damage in NTEs than that in TEs. By comparing the model results with experimental data, we found that signal-induced DNA damage and lower repair efficiency in non-hit cells are responsible for NTE-related repair kinetics of DNA damage, cell survival curve with low-dose hyper-radiosensitivity (HRS) and MTBEs. From the standpoint of modelling, the integrated cell-killing model with the LQ relation and a different repair function for NTEs provide a reasonable signal-emission probability and a new estimation of low-dose HRS linked to DNA repair efficiency.

SUBMITTER: Matsuya Y

PROVIDER: S-EPMC5859303 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature

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Integrated Modelling of Cell Responses after Irradiation for DNA-Targeted Effects and Non-Targeted Effects.

Matsuya Yusuke Y Sasaki Kohei K Yoshii Yuji Y Okuyama Go G Date Hiroyuki H

Scientific reports 20180319 1

Intercellular communication after ionizing radiation exposure, so-called non-targeted effects (NTEs), reduces cell survival. Here we describe an integrated cell-killing model considering NTEs and DNA damage along radiation particle tracks, known as DNA-targeted effects (TEs) based on repair kinetics of DNA damage. The proposed model was applied to a series of experimental data, i.e., signal concentration, DNA damage kinetics, cell survival curve and medium transfer bystander effects (MTBEs). To ...[more]

PMID: 29555939

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Project description:The biological effects of chronic ionizing radiation exposure can be difficult to study, but important to understand in order to protect the health of occupationally-exposed persons and victims of radiological accidents or malicious events. They include targeted effects (TE) caused by ionizations within/close to nuclear DNA, and non-targeted effects (NTE) caused by damage to other cell structures and/or activation of stress-signaling pathways in distant cells. Data on radiation damage in animal populations exposed over multiple generations to wide ranges of dose rates after the Chernobyl nuclear-power-plant accident are very useful for enhancing our understanding of these processes. We used a mechanistically-motivated mathematical model which includes TE and NTE to analyze a large published data set on chromosomal aberrations in pond snail (Lymnaea stagnalis) embryos collected over 16 years from water bodies contaminated by Chernobyl fallout, and from control locations. The fraction of embryo cells with aberrations increased dramatically (>10-fold) and non-linearly over a dose rate range of 0.03-420 μGy/h (0.00026-3.7 Gy/year). NTE were very important for describing the non-linearity of this radiation response: the TE-only model (without NTE) performed dramatically worse than the TE+NTE model. NTE were predicted to reach ½ of maximal intensity at 2.5 μGy/h (0.022 Gy/year) and to contribute >90% to the radiation response slope at dose rates <11 μGy/h (0.1 Gy/year). Internally-incorporated 90Sr was possibly more effective per unit dose than other radionuclides. The radiation response shape for chromosomal aberrations in snail embryos was consistent with data for a different endpoint: the fraction of young amoebocytes in adult snail haemolymph. Therefore, radiation may affect different snail life stages by similar mechanisms. The importance of NTE in our model-based analysis suggests that the search for modulators of NTE-related signaling pathways could be a promising strategy for mitigating the deleterious effects of chronic irradiation.

Dataset Information

Integrated Modelling of Cell Responses after Irradiation for DNA-Targeted Effects and Non-Targeted Effects.

Publications

Integrated Modelling of Cell Responses after Irradiation for DNA-Targeted Effects and Non-Targeted Effects.

Similar Datasets

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