title: Radiation-induced bystander effect in non-irradiated glioblastoma spheroid cells.
abstract: Radiation-induced bystander effects (RIBEs) are detected in cells that are not irradiated but receive signals from treated cells. The present study explored these bystander effects in a U87MG multicellular tumour spheroid model. A medium transfer technique was employed to induce the bystander effect, and colony formation assay was used to evaluate the effect. Relative changes in expression of BAX, BCL2, JNK and ERK genes were analysed using RT-PCR to investigate the RIBE mechanism. A significant decrease in plating efficiency was observed for both bystander and irradiated cells. The survival fraction was calculated for bystander cells to be 69.48% and for irradiated cells to be 34.68%. There was no change in pro-apoptotic BAX relative expression, but anti-apoptotic BCL2 showed downregulation in both irradiated and bystander cells. Pro-apoptotic JNK in bystander samples and ERK in irradiated samples were upregulated. The clonogenic survival data suggests that there was a classic RIBE in U87MG spheroids exposed to 4 Gy of X-rays, using a medium transfer technique. Changes in the expression of pro- and anti-apoptotic genes indicate involvement of both intrinsic apoptotic and MAPK pathways in inducing these effects.
authors.affiliation: Radiation Sciences Department, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Fahime
authors.initials: F
authors.lastname: Faqihi
authors.affiliation: Radiation Sciences Department, Faculty of Medical Physics, Iran University of Medical Sciences, Tehran, Iran neshastehriz@yahoo.com.
authors.forename: Ali
authors.initials: A
authors.lastname: Neshastehriz
authors.affiliation: Medical Physics Department, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Shokouhozaman
authors.initials: S
authors.lastname: Soleymanifard
authors.affiliation: Cellular and Molecular Research Center, Iran University of Medical Sciences, Tehran, Iran.
authors.forename: Robabeh
authors.initials: R
authors.lastname: Shabani
authors.affiliation: Radiation Research Center, a.ja University of Medical Sciences, Tehran, Iran.
authors.forename: Nazila
authors.initials: N
authors.lastname: Eivazzadeh
mesh_terms: D017209:Apoptosis; D024201:Bystander Effect; D045744:Cell Line, Tumor; D002470:Cell Survival; D005909:Glioblastoma / Q000473:pathology / Q000532:radiotherapy*; D006801:Humans; D048670:MAP Kinase Kinase 4 / Q000378:metabolism; D020935:MAP Kinase Signaling System; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D011878:Radiotherapy; D018874:Spheroids, Cellular / Q000166:cytology*; D014965:X-Rays; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: C494826:BAX protein, human; C000595707:BCL2 protein, human; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D048670:MAP Kinase Kinase 4
keywords: U87MG spheroid; apoptosis; radiation-induced bystander effect