Abstract
Here we have investigated bystander response of human fibroblasts to energetic heavy ions in confluent cultures. First, 0.0003% of cells were targeted with microbeams. Broadbeam irradiation was also conducted to see the effects in irradiated cells. Bystander cells manifested a more transient apoptotic response and delayed p53 phosphorylation compared with irradiated cells. More than half of the genes whose expression changed in bystander cells were downregulated, and most of the genes upregulated in irradiated cells were downregulated in bystander cells. Pathway analysis revealed serial activation of p21Waf1 and NF-κB pathways in irradiated cells but G protein/PI-3 kinase pathway in bystander cells. These findings highlight the distinct response of irradiated and bystander cells. Moreover, interleukin genes were upregulated in irradiated cells but its receptor gene was upregulated in bystander cells, suggestive of the signal transmission from irradiated to bystander cells. Second, as regards chromosome aberrations in bystander cells treated with conditioned medium from X- or heavy ion-irradiated cells, we found the difference in the types of aberrations but little difference in its total yields, indicating that bystander responses occur independently of radiation types but are induced through different mechanisms. Altogether, these induced bystander responses could be a defensive mechanism that would minimize further expansion of aberrant cells. [Refs] JRR (2007) 48:87-95. IJRB (2007) 83:73-80. Mutat Res (2008) 637:190-196, 639:35-44, 642:57-67.
