Bystander Effects in the Cellular Radiation Response

The overall response to tumor radiation therapy results from direct radiation damage and indirect bystander effects (RIBE) mediated by secreted molecules and paracrine transfer of short-lived mediators. RIBE can have both detrimental and protective actions on cancerous as well as healthy tissues. Nuclear Factor κB (NF-κB), which governs immune responses, is a prime candidate for mediating RIBE. NF-κB also modulates DNA repair while promoting cellular survival as part of the DNA damage response. After exposure to ionizing radiation NF-κB is activated in directly targeted and non-targeted bystander cells. We tested the hypothesis that the NF-κB status is relevant for induction of RIBE, using a mouse embryonal fibroblasts (MEF) knock-out variant that is unable to activate NF-κB (NF-κB essential modulator knock-out (NEMO ko)).