A kinetic-based model of radiation-induced intercellular signalling.
It is now widely accepted that intercellular communication can cause significant variations in cellular responses to genotoxic stress. The radiation-induced bystander effect is a prime example of this effect, where cells shielded from radiation exposure see a significant reduction in survival when cultured with irradiated cells. However, there is a lack of robust, quantitative models of this effect which are widely applicable. In this work, we present a novel mathematical model of radiation-induced intercellular signalling which incorporates signal production and response kinetics together with the effects of direct irradiation, and test it against published data sets, including modulated field exposures. This model suggests that these so-called "bystander" effects play a significant role in determining cellular survival, even in directly irradiated populations, meaning that the inclusion of intercellular communication may be essential to produce robust models of radio-biological outcomes in clinically relevant in vivo situations.
Centre for Cancer Research and Cell Biology, Queen's University Belfast, Belfast, Northern Ireland, United Kingdom. stephen.mcmahon@qub.ac.uk
Stephen J
SJ
McMahon
Karl T
KT
Butterworth
Colman
C
Trainor
Conor K
CK
McGarry
Joe M
JM
O'Sullivan
Giuseppe
G
Schettino
Alan R
AR
Hounsell
Kevin M
KM
Prise
D024201:Bystander Effect; D002450:Cell Communication / Q000528:radiation effects*; D002470:Cell Survival / Q000528:radiation effects; D004249:DNA Damage; D006801:Humans; D007700:Kinetics; D008962:Models, Theoretical; D011827:Radiation; D015398:Signal Transduction / Q000528:radiation effects