Interaction between Radioadaptive Response and Radiation-Induced Bystander Effect in Caenorhabditis elegans : A Unique Role of the DNA Damage Checkpoint

Abstract

Although radioadaptive responses (RAR) and radiation-induced bystander effects (RIBE) are two important biological effects of low-dose radiation, there are currently only limited data that directly address their interaction, particularly in the context of whole organisms. In previous studies, we separately demonstrated RAR and RIBE using an in vivo system of C. elegans . In the current study, we further investigated their interaction in C. elegans , with the ratio of protruding vulva as the biological end point for RAR. Fourteen-hour-old worms were first locally targeted with a proton microbeam, and were then challenged with a high dose of whole-body gamma radiation. Microbeam irradiation of the posterior pharynx bulbs and rectal valves of C. elegans could significantly suppress the induction of protruding vulva by subsequent gamma irradiation, suggesting a contribution of RIBE to RAR in the context of the whole organism. Moreover, C. elegans has a unique DNA damage response in which the upstream DNA damage checkpoint is not active in most of somatic cells, including vulval cells. However, its impairment in atm-1 and hus-1 mutants blocked the RIBE-initiated RAR of vulva. Similarly, mutations in the atm-1 and hus-1 genes inhibited the RAR of vulva initiated by microbeam irradiation of the vulva itself. These results further confirm that the DNA damage checkpoint participates in the induction of RAR of vulva in C. elegans in a cell nonautonomous manner.