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A reaction-diffusion model for radiation-induced bystander effects.

Oluwole Olobatuyi1, Gerda de Vries2, Thomas Hillen2

  • 1Centre for Mathematical Biology, Mathematical and Statistical Sciences, University of Alberta, Edmonton, T6G2G1, Canada. olobatuy@ualberta.ca.

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|December 31, 2016
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Summary

A mathematical model confirms that radiation-induced bystander signals can persist, potentially explaining low-dose hyper-radiosensitivity and increased radioresistance (HRS/IRR) by influencing cell death dynamics.

Keywords:
Bystander effectsCytochrome complexHyper-radiosensitivityIncreased radioresistanceRadiation-induced bystander signalReaction–diffusion model

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Area of Science:

  • Radiation biology
  • Mathematical modeling
  • Cellular signaling

Background:

  • Cellular exposure to radiation can trigger bystander effects mediated by emitted signals.
  • These signals have been observed to persist for extended periods, from hours to years.
  • Bystander effects are hypothesized to contribute to low-dose hyper-radiosensitivity and increased radioresistance (HRS/IRR).

Purpose of the Study:

  • To develop and analyze a reaction-diffusion model for radiation-induced bystander signal dynamics.
  • To mathematically confirm the hypothesis linking bystander signals to HRS/IRR.
  • To investigate factors influencing bystander signal lifespan and associated cell death.

Main Methods:

  • Development and analysis of a reaction-diffusion model.
  • Fitting the model to experimental data (Joiner's data on T98G glioma cells).
  • Phase plane analysis and sensitivity analysis.

Main Results:

  • The model confirms that radiation-induced bystander signals can persist, supporting the HRS/IRR hypothesis.
  • Both single and multiple radiation exposures can result in temporary or permanent signal persistence.
  • Environmental factors like radiation domain size and exposure number influence signal persistence in heterogeneous environments.

Conclusions:

  • Mathematical modeling provides a framework for understanding bystander signal dynamics and their role in radiobiology.
  • The persistence and characteristics of bystander signals are crucial for explaining phenomena like HRS/IRR.
  • Cellular parameters significantly impact signal lifespan and radiation-induced cell death, offering targets for further research.