title: Signaling factors for irradiated glioma cells induced bystander responses in fibroblasts.
abstract: The aim of this study was to investigate the signaling factor and its pathway involved in the targeted irradiation-induced bystander response from glioblastoma cells to primary fibroblasts. After co-culturing with a glioblastoma T98G population where a fraction of cells had been individually irradiated with a precise number of helium particles, additional micronucleus (MN) were induced in the non-irradiated human fibroblasts AG01522 cells and its yield was independent of irradiation dose. This bystander MN induction was eliminated by treating the cells with either aminoguanidine (AG), an iNOS inhibitor, or anti-transforming growth factor-beta1 (anti-TGF-beta1). In addition, TGF-beta1 could be released from irradiated T98G cells but this release was inhibited by AG. In consistent, TGF-beta1 could also be induced from T98G cells treated with diethylamine nitric oxide (DEANO), a donor of nitric oxide (NO). Moreover, the effect of TGF-beta1 on bystander AG01522 cells was investigated. It was found that reactive oxygen species (ROS) and MN were induced in AG01522 cells after TGF-beta1 treatment. Our results indicate that, downstream of NO, TGF-beta1 plays an important role in the targeted T98G cells induced bystander response to AG0 cells by further causing DNA damage in vicinal fibroblasts through a ROS related pathway. This study may have implications for properly evaluating the secondary effects of radiotherapy.
authors.affiliation: Institute of Radiation Medicine, Fudan University, No. 2094 Xie-Tu Road, Shanghai 200032, China. clshao@shmu.edu.cn
authors.forename: Chunlin
authors.initials: C
authors.lastname: Shao
authors.forename: Kevin M
authors.initials: KM
authors.lastname: Prise
authors.forename: Melvyn
authors.initials: M
authors.lastname: Folkard
mesh_terms: D024201:Bystander Effect; D018920:Coculture Techniques; D004249:DNA Damage / Q000528:radiation effects*; D005347:Fibroblasts / Q000378:metabolism / Q000528:radiation effects*; D005909:Glioblastoma / Q000378:metabolism*; D006371:Helium; D006801:Humans; D048629:Micronuclei, Chromosome-Defective; D009569:Nitric Oxide / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*
chemical_list: D017382:Reactive Oxygen Species; D053773:Transforming Growth Factor beta1; D006371:Helium; D009569:Nitric Oxide