title: Bystander effects and their implications for clinical radiation therapy: Insights from multiscale in silico experiments.
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 phenomena, may 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 paper, 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 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.
authors.affiliation: Department of Mathematics, Swansea University, Swansea SA2 8PP, UK. Electronic address: g.g.powathil@swansea.ac.uk.
authors.forename: Gibin G
authors.initials: GG
authors.lastname: Powathil
authors.affiliation: Radiation Oncology, Division of Cancer Research, University of Dundee, Ninewells Hospital and Medical School, Dundee DD1 9SY, UK.
authors.forename: Alastair J
authors.initials: AJ
authors.lastname: Munro
authors.affiliation: School of Mathematics and Statistics, University of St Andrews, St Andrews KY16 9SS, UK.
authors.forename: Mark A J
authors.initials: MA
authors.lastname: Chaplain
authors.affiliation: The Biocomplexity Institute and Department of Physics, Indiana University Bloomington, Bloomington, Indiana, USA.
authors.forename: Maciej
authors.initials: M
authors.lastname: Swat
mesh_terms: D000818:Animals; D024201:Bystander Effect / Q000528:radiation effects*; D003198:Computer Simulation; D004249:DNA Damage; D006801:Humans; D008954:Models, Biological; D011836:Radiation Tolerance; D011878:Radiotherapy / Q000009:adverse effects*
keywords: Cell-cycle; Multiscale mathematical model; Radiation therapy; Radiation-induced bystander effects