title: A theoretical approach to the role and critical issues associated with bystander effect in risk estimation.
abstract: This paper presents a quantitative biophysical model of the radiation-induced bystander effect. The principle aim of the bystander model is to establish whether bystander signal can be associated with low molecular weight factors that are transmitted by diffusion type processes in the medium surrounding the recipient cells. Cell inactivation and induced oncogenic transformation by microbeam and broadbeam irradiation systems were considered. The biophysical model 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. The bystander cell survival observed after treatment with the irradiated conditioned medium using broadbeam and the microbeam irradiation modalities were analysed and interpreted in the framework of the Bystander Diffusion Model (BSDM). The model predictions for cell inactivation and induced oncogenic transformation frequencies agree well with observed data from microbeam and broadbeam experiments. In the case of irradiation with constant fraction of cells, transformation frequency for the bystander effect increases with increasing radiation dose. 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 can be observed at high doses as well as low doses. The validity of this conclusion is supported by analysis of experimental results from high-LET microbeam experiments.
authors.affiliation: MRC Radiation and Genome Stability Unit, Harwell, OX11 0RD, UK. h.nikjoo@har.mrc.ac.uk
authors.forename: Hooshang
authors.initials: H
authors.lastname: Nikjoo
authors.forename: Igor K
authors.initials: IK
authors.lastname: Khvostunov
mesh_terms: D000222:Adaptation, Physiological; D000818:Animals; D024201:Bystander Effect / Q000528:radiation effects*; D002471:Cell Transformation, Neoplastic; D006801:Humans; D018499:Linear Energy Transfer; D018570:Risk Assessment; D015398:Signal Transduction