Bystander effects of alfa-radiation

The universality of the target theory of radiation-induced effects is challenged by observations on non-targeted effects such as bystander effects, genomic instability and adaptive response. Essential features of non-targeted effects are that they do not require direct nuclear exposure by radiation and they are particularly significant at low doses. This new evidence suggests a need for a new paradigm in radiation biology. The new theory should cover both the classical (targeted) and the non-targeted effe cts, including cellular communication and tissue-level responses. This project is an integrated part of the NOTE consortium. The general objective of is to explore the mechanisms involved in the bystander effect of alpha-radiation. We propose to address this question by employing a low-dose broad and narrow field irradiation approach to investigate both alpha- and X-radiation responses, using human cell cultures. Mechanistically, we plan to study bystander-induced cell death, oxidative stress and DNA rep air and compare the results of these studies with genome wide gene expression in bystander cells. Furthermore, siRNA will be used to inhibit differential expression of selected genes to clearly define the role of these genes in cell cycle regulation, DNA repair and cell death of bystander cells. Inhibitors of selected signal transduction pathways will be used to modulate the alpha-radiation-induced bystander effect to determine the contribution of intercellular communication. Mathematical modelling and us e of bioinformatics methods will be an integrated part of the project.