A biophysical model of cell evolution after cytotoxic treatments: damage, repair and cell response

DOI10.1016/J.JTBI.2015.10.017zbMATH Open1343.92136arXiv1509.06304OpenAlexW2964052250WikidataQ40343108 ScholiaQ40343108MaRDI QIDQ304752FDOQ304752

Authors: M. Tomezak, C. Abbadie, E. Lartigau, F. Cleri 

Publication date: 26 August 2016

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

Abstract: We present a theoretical agent-based model of cell evolution under the action of cytotoxic treatments, such as radioteraphy or chemoteraphy. The major features of cell cycle and proliferation, cell damage and repair, and chemical diffusion are included. Cell evolution is based on a discrete Markov chain, with cells stepping along a sequence of discrete internal states from 'normal' to 'inactive'. Probabilistic laws are introduced for each type of event a cell can undergo during its life cycle: duplication, arrest, apoptosis, senescence, damage, healing. We adjust the model parameters on a series of cell irradiation experiments, carried out in a clinical LINAC at 20 MV, in which the damage and repair kinetics of single- and double-strand breaks are followed. Two showcase applications of the model are then presented. In the first one, we reconstruct the cell survival curves from a number of published low- and high-dose irradiation experiments. We reobtain a very good description of the data without assuming the well-known linear-quadratic model, but instead including a variable DSB repair probability, which is found to spontaneously saturate with an exponential decay at increasingly high doses. As a second test, we attempt to simulate the two extreme possibilities of the so-called 'bystander' effect in radiotherapy: the 'local' effect versus a 'global' effect, respectively activated by the short-range or long-range diffusion of some factor, presumably secreted by the irradiated cells. Even with an oversimplified simulation, we could demonstrate a sizeable difference in the proliferation rate of non-irradiated cells, the proliferation acceleration being much larger for the global than the local effect, for relatively small fractions of irradiated cells in the colony.

Full work available at URL: https://arxiv.org/abs/1509.06304

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zbMATH Keywords

agent-based modellingbystander effectcancer radiotherapycell population modellingcell survival curves

Mathematics Subject Classification ID

Medical applications (general) (92C50) Cell biology (92C37)

Cites Work

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Cited In (6)

• A numerical model of EMT6/Ro spheroid dynamics under irradiation: calibration and estimation of the underlying irradiation-induced cell survival probability
• Bystander effects and their implications for clinical radiation therapy: insights from multiscale \textit{in silico} experiments
• A dynamical model of oncotripsy by mechanical cell fatigue: selective cancer cell ablation by low-intensity pulsed ultrasound
• Additive damage models for cellular pharmacodynamics of radiation-chemotherapy combinations
• A branching process model of heterogeneous DNA damages caused by radiotherapy in \textit{in vitro} cell cultures
• Models for the bystander effect in gradient radiation fields: range and signalling type

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