Triggering-Response Model for Radiation-Induced Bystander Effects

Abstract

Fakir, H., Hofmann, W., Tan, W. Y. and Sachs, R. K. Triggering-Response Model for Radiation-Induced Bystander Effects. Radiat. Res. 171, 320–331 (2009). We propose a mechanistic model for radiation cell killing and carcinogenesis-related end points that combines direct and bystander responses. The model describes the bystander component as a sequence of two distinct processes: triggering of signal emission from irradiated cells and response of nonirradiated recipient cells; in principle it can incorporate microdosimetric information as well as the random aspects of signal triggering and recipient response. Late effects are modeled using a one-stage model based on the concepts of inactivation and initiation, which allows for the proliferation of normal and initiated cells; proliferation of initiated cells is analyzed using a stochastic, birth-death approach. The model emphasizes the dependence of bystander effects on dose, which is important for the assessment of low-dose cancer induction by extrapolations of risk from high-dose exposures. The results obtained show adequate agreement with different in vitro bystander experiments involving ultrasoft X rays and α particles and correctly reflect the main features observed for several end points. Our results suggest signal transmission through the medium rather than gap junctions. We suggest that for many such experiments, a moderate increase in medium volume should have about the same effect as a moderate decrease in the fraction of irradiated cells.