Bystander effects and their implications for clinical radiation therapy: insights from multiscale \textit{in silico} experiments

DOI10.1016/J.JTBI.2016.04.010MaRDI QIDQ738646zbMATH OpenOpenAlexWikidataFDO

Authors Gibin G. Powathil, Alastair J. Munro, Maciej Swat, M. A. J. Chaplain

Publication date 5 September 2016

Published in Journal of Theoretical Biology (Search for Journal in Brave)

Full work available at URL https://arxiv.org/abs/1407.0867

zbMATH Keywords

radiation therapycell-cyclemultiscale mathematical modelradiation-induced bystander effects

Mathematics Subject Classification ID

Computational methods for problems pertaining to biology (92-08) Cell biology (92C37)

Abstract: Radiotherapy is a commonly used treatment for cancer and is usually given in varying doses. At low radiation doses relatively few cells die as a direct response to radiation but secondary radiation effects such as DNA mutation or bystander effects affect many cells. Consequently it is at low radiation levels where an understanding of bystander effects is essential in designing novel therapies with superior clinical outcomes. In this article, we use a hybrid multiscale mathematical model to study the direct effects of radiation as well as radiation-induced bystander effects on both tumour cells and normal cells. We show that bystander responses may play a major role in mediating radiation damage to cells at low-doses of radiotherapy, doing more damage than that due to direct radiation. The survival curves derived from our computational simulations showed an area of hyper-radiosensitivity at low-doses that are not obtained using a traditional radiobiological model.

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Cites work

• A model for radiation-induced bystander effects, with allowance for spatial position and the effects of cell turnover
• A model for restriction point control of the mammalian cell cycle
• Modeling the spatial distribution of chronic tumor hypoxia: implications for experimental and clinical studies
• Modelling the effects of cell-cycle heterogeneity on the response of a solid tumour to chemotherapy: biological insights from a hybrid multiscale cellular automaton model

Cited in

(8)

• A model for radiation-induced bystander effects, with allowance for spatial position and the effects of cell turnover
• Effects of G2-checkpoint dynamics on low-dose hyper-radiosensitivity
• A simulation study of the radiation-induced bystander effect: modeling with stochastically defined signal reemission
• Predicting radiotherapy patient outcomes with real-time clinical data using mathematical modelling
• In silico nanodosimetry: new insights into nontargeted biological responses to radiation
• A reaction-diffusion model for radiation-induced bystander effects
• Models for the bystander effect in gradient radiation fields: range and signalling type
• Regulation of p53 by SIRNA in radiation treated cells: simulation studies

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