Spatial function of the oxidative DNA damage response in radiation induced bystander effects in intra- and inter-system of Caenorhabditis elegans

Abstract

Though the signaling events involved in radiation induced bystander effects (RIBE) have been investigated both in vitro and in vivo, the spatial function of these communications, especially the related signaling pathways, is not fully elucidated. In the current study, significant increases of DNA damage were clearly observed in C. elegans germline upon irradiation to both intra-system of posterior pharynx and inter-system of vulva, in which more severe damage, even to F1 generation worms, was shown for vulva irradiation. Spatial function assay indicated the DDR key components of mrt-2/hus-1/cep-1/ced-4 were indispensable in germ cells for both sites irradiation, while those components in somatic cells were either not (cep-1/ced-4) or partially (mrt-2/hus-1) required to promote apoptosis. Moreover, production of reactive oxygen species (ROS) indicated by the superoxide dismutase expression and the unfolded protein response of the mitochondria was found systemically involved in the initiation of these processes for both two site irradiation. These results will give a better understanding of the RIBE mechanisms in vivo, and invaluable to assess the clinical relevance to radiotherapy.