Biophysical model of the radiation-induced bystander effect.
OBJECTIVE
To construct a quantitative model of the radiation-induced bystander effect based on diffusion-type spreading of bystander signal communication between the hit and non-hit cells. Cell inactivation and induced oncogenic transformation by broad- and microbeam irradiation systems are considered.


METHODS
The biophysical model ByStander Diffusion Modelling (BSDM) postulates that the oncogenic bystander response observed in non-hit cells originates from specific signals received from inactivated cells. The bystander signals are assumed to be protein-like molecules spreading in the culture media by Brownian motion. The bystander signals are assumed to switch cells into a state of cell death (apoptotic/mitotic/necrosis) or induced oncogenic transformation modes.


RESULTS
The bystander cell survival observed after treatment with the irradiated conditioned medium (ICM) using the broad-beam and the microbeam irradiation modalities were analysed and interpreted in the framework of the BSDM model. The model predictions for cell inactivation and induced oncogenic transformation frequencies agree well with observed data from micro and broad-beam experiments. In the case of irradiation with constant fraction of cells, transformation frequency for the bystander effect increases with increasing radiation dose.


CONCLUSIONS
Bystander modelling based on diffusion of signals is in good agreement with experimental cell survival data and induced oncogenic transformation frequencies. The data confirm the protein-like nature of the bystander signal. Linear extrapolation of the cell response to low doses of radiation might underestimate carcinogenic risk, for example for domestic radon hazards, if the contribution from the bystander effect is neglected. The BSDM predicts that the bystander effect cannot be interpreted solely as a low-dose effect phenomenon. It is shown that the bystander component of radiation response can increase with dose and be observed at high doses as well as at low doses. The validity of this conclusion is supported by analysis of experimental results from high-linear energy transfer microbeam experiments.
Nikjoo
Hooshang
H
MRC Radiation & Genome Stability Unit, Harwell OX11 0RD, UK. h.nikjoo@har.mrc.ac.uk
Khvostunov
Igor K
IK
D000512:Alpha Particles; D000818:Animals; D024201:Bystander Effect / Q000528:radiation effects*; D002460:Cell Line; D002470:Cell Survival / Q000528:radiation effects*; D002471:Cell Transformation, Neoplastic; D051379:Mice; D008954:Models, Biological