Detrimental and Protective Bystander Effects: A Model Approach

Schöllnberger, H., Mitchel, R. E. J., Redpath, J. L., Crawford-Brown, D. J. and Hofmann, W. Detrimental and Protective Bystander Effects: A Model Approach. Radiat. Res. 168, 614–626 (2007). This work integrates two important cellular responses to low doses, detrimental bystander effects and apoptosis-mediated protective bystander effects, into a multistage model for chromosome aberrations and in vitro neoplastic transformation: the State-Vector Model. The new models were tested on representative data sets that show supralinear or U-shaped dose responses. The original model without the new low-dose features was also tested for consistency with LNT-shaped dose responses. Reductions of in vitro neoplastic transformation frequencies below the spontaneous level have been reported after exposure of cells to low doses of low-LET radiation. In the current study, this protective effect is explained with bystander-induced apoptosis. An important data set that shows a low-dose detrimental bystander effect for chromosome aberrations was successfully fitted by additional terms within the cell initiation stage. It was found that this approach is equivalent to bystander-induced clonal expansion of initiated cells. This study is an important step toward a comprehensive model that contains all essential biological mechanisms that can influence dose–response curves at low doses.