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

Overview

Journal Sci Rep

Specialty Science

Date 2018 Mar 21

PMID 29555939

Citations 12

Authors

Yusuke Matsuya

Kohei Sasaki

Yuji Yoshii

Go Okuyama

Hiroyuki Date

Affiliations

Soon will be listed here.

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.

Citing Articles

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References

Nagasawa H, Little J . Induction of sister chromatid exchanges by extremely low doses of alpha-particles. Cancer Res. 1992; 52(22):6394-6. View

Burdak-Rothkamm S, Short S, Folkard M, Rothkamm K, Prise K . ATR-dependent radiation-induced gamma H2AX foci in bystander primary human astrocytes and glioma cells. Oncogene. 2006; 26(7):993-1002. DOI: 10.1038/sj.onc.1209863. View

Guirado D, Aranda M, Ortiz M, Mesa J, Zamora L, Amaya E . Low-dose radiation hyper-radiosensitivity in multicellular tumour spheroids. Br J Radiol. 2012; 85(1018):1398-406. PMC: 3474031. DOI: 10.1259/bjr/33201506. View

Kundrat P, Friedland W . Track structure calculations on intracellular targets responsible for signal release in bystander experiments with transfer of irradiated cell-conditioned medium. Int J Radiat Biol. 2011; 88(1-2):98-102. DOI: 10.3109/09553002.2011.595874. View

Hausmann M, Winkler R, Hildenbrand G, Finsterle J, Weisel A, Rapp A . COMBO-FISH: specific labeling of nondenatured chromatin targets by computer-selected DNA oligonucleotide probe combinations. Biotechniques. 2003; 35(3):564-70, 572-7. DOI: 10.2144/03353rr03. View

Edin N, Olsen D, Sandvik J, Malinen E, Pettersen E . Low dose hyper-radiosensitivity is eliminated during exposure to cycling hypoxia but returns after reoxygenation. Int J Radiat Biol. 2011; 88(4):311-9. DOI: 10.3109/09553002.2012.646046. View

Kashino G, Prise K, Schettino G, Folkard M, Vojnovic B, Michael B . Evidence for induction of DNA double strand breaks in the bystander response to targeted soft X-rays in CHO cells. Mutat Res. 2004; 556(1-2):209-15. DOI: 10.1016/j.mrfmmm.2004.08.009. View

Chalmers A, Johnston P, Woodcock M, Joiner M, Marples B . PARP-1, PARP-2, and the cellular response to low doses of ionizing radiation. Int J Radiat Oncol Biol Phys. 2004; 58(2):410-9. DOI: 10.1016/j.ijrobp.2003.09.053. View

Marples B, Joiner M . The elimination of low-dose hypersensitivity in Chinese hamster V79-379A cells by pretreatment with X rays or hydrogen peroxide. Radiat Res. 1995; 141(2):160-9. View

10.

Hawkins R . A microdosimetric-kinetic model of cell death from exposure to ionizing radiation of any LET, with experimental and clinical applications. Int J Radiat Biol. 1996; 69(6):739-55. DOI: 10.1080/095530096145481. View

11.

Sasaki K, Wakui K, Tsutsumi K, Itoh A, Date H . A simulation study of the radiation-induced bystander effect: modeling with stochastically defined signal reemission. Comput Math Methods Med. 2012; 2012:389095. PMC: 3502842. DOI: 10.1155/2012/389095. View

12.

Rothkamm K, Lobrich M . Evidence for a lack of DNA double-strand break repair in human cells exposed to very low x-ray doses. Proc Natl Acad Sci U S A. 2003; 100(9):5057-62. PMC: 154297. DOI: 10.1073/pnas.0830918100. View

13.

Botchway S, Stevens D, Hill M, Jenner T, ONeill P . Induction and rejoining of DNA double-strand breaks in Chinese hamster V79-4 cells irradiated with characteristic aluminum K and copper L ultrasoft X rays. Radiat Res. 1997; 148(4):317-24. View

14.

Hawkins R . A statistical theory of cell killing by radiation of varying linear energy transfer. Radiat Res. 1994; 140(3):366-74. View

15.

Matsuya Y, Tsutsumi K, Sasaki K, Yoshii Y, Kimura T, Date H . Modeling cell survival and change in amount of DNA during protracted irradiation. J Radiat Res. 2016; 58(3):302-312. PMC: 5465389. DOI: 10.1093/jrr/rrw110. View

16.

Chou C, Chen P, Lee P, Cheng A, Hsu H, Cheng J . Radiation-induced hepatitis B virus reactivation in liver mediated by the bystander effect from irradiated endothelial cells. Clin Cancer Res. 2007; 13(3):851-7. DOI: 10.1158/1078-0432.CCR-06-2459. View

17.

McMahon S, Butterworth K, Trainor C, McGarry C, OSullivan J, Schettino G . A kinetic-based model of radiation-induced intercellular signalling. PLoS One. 2013; 8(1):e54526. PMC: 3551852. DOI: 10.1371/journal.pone.0054526. View

18.

Seymour C, Mothersill C . Relative contribution of bystander and targeted cell killing to the low-dose region of the radiation dose-response curve. Radiat Res. 2000; 153(5 Pt 1):508-11. DOI: 10.1667/0033-7587(2000)153[0508:rcobat]2.0.co;2. View

19.

Ojima M, Furutani A, Ban N, Kai M . Persistence of DNA double-strand breaks in normal human cells induced by radiation-induced bystander effect. Radiat Res. 2010; 175(1):90-6. DOI: 10.1667/RR2223.1. View

20.

Nagasawa H, Huo L, Little J . Increased bystander mutagenic effect in DNA double-strand break repair-deficient mammalian cells. Int J Radiat Biol. 2003; 79(1):35-41. View