No abstract

Reproductive cell death (RCD) occurs after one or more cell divisions resulting from an insult such as radiation exposure or other treatments with carcinogens or mutagens. The radioadaptive response for RCD is usually investigated by in vitro or in vivo clonogenic assay. To date, this has not been demonstrated in the vulval tissue in Caenorhabditis elegans ( C. elegans ), which is a well established in vivo model for radiation-induced RCD. In this study to determine whether radioadaptive response occurs in the vulval tissue model of C. elegans , early larval worms were gamma irradiated with lower adaptive doses, followed by higher challenge doses. The ratio of protruding vulva was used to assess the RCD of vulval cells. The results of this study showed that the radioadaptive response for RCD in this vulval tissue model could be well induced by dose combinations of 5 + 75 Gy and 5 + 100 Gy at the time point of 14-16 h in worm development. In addition, the time course analysis indicated that radioresistance in vulval cells developed within 1.75 h after an adaptive dose and persisted for only a short period of time (2-4 h). DNA damage checkpoint and non-homologous end joining were involved in the radioadaptive response, exhibiting induction of protruding vulva in worms deficient in these two pathways similar to their controls. Interestingly, the DNA damage checkpoint was not active in the somatic vulval cells, and it was therefore suggested that the DNA damage checkpoint might mediate the radioadaptive response in a cell nonautonomous manner. Here, we show evidence of the occurrence of a radioadaptive response for RCD in the vulval tissue model of C. elegans . This finding provides a potential opportunity to gain further insight into the underlying mechanisms of the radioadaptive response for RCD, in view of the abundant genetic resources of C. elegans .

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.