The Bystander Effect in Radiation Oncogenesis: II. A Quantitative Model

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Abstract
Brenner, D. J., Little, J. B. and Sachs, R. K. The Bystander Effect in Radiation Oncogenesis: II. A Quantitative Model. There is strong evidence that biological response to ionizing radiation has a contribution from unirradiated “bystander” cells that respond to signals emitted by irradiated cells. We discuss here an approach incorporating a radiobiological bystander response, superimposed on a direct response due to direct energy deposition in cell nuclei. A quantitative model based on this approach is described for α-particle-induced in vitro oncogenic transformation. The model postulates that the oncogenic bystander response is a binary “all or nothing” phenomenon in a small sensitive subpopulation of cells, and that cells from this sensitive subpopulation are also very sensitive to direct hits from α particles, generally resulting in a directly hit sensitive cell being inactivated. The model is applied to recent data on in vitro oncogenic transformation produced by broad-beam or microbeam α-particle irradiation. Two parameters are used in analyzing the data for transformation frequency. The analysis suggests that, at least for α-particle-induced oncogenic transformation, bystander effects are important only at small doses—here below about 0.2 Gy. At still lower doses, bystander effects may dominate the overall response, possibly leading to an underestimation of low-dose risks extrapolated from intermediate doses, where direct effects dominate.