title: Possible role of exosomes containing RNA in mediating nontargeted effect of ionizing radiation.
abstract: Communication between irradiated and un-irradiated (bystander) cells can cause damage in cells that are not directly targeted by ionizing radiation, a process known as the bystander effect. Bystander effects can also lead to chromosomal/genomic instability within the progeny of bystander cells, similar to the progeny of directly irradiated cells. The factors that mediate this cellular communication can be transferred between cells via gap junctions or released into the extracellular media following irradiation, but their nature has not been fully characterized. In this study we tested the hypothesis that the bystander effect mediator contains an RNA molecule that may be carried by exosomes. MCF7 cells were irradiated with 2 Gy of X rays and the extracellular media was harvested. RNase treatment abrogated the ability of the media to induce early and late chromosomal damage in bystander cells. Furthermore, treatment of bystander cells with exosomes isolated from this media increased the levels of genomic damage. These results suggest that the bystander effect, and genomic instability, are at least in part mediated by exosomes and implicate a role for RNA.
authors.affiliation: Department of Biological and Medical Sciences, Faculty of Health and Life Sciences, Oxford Brookes University, Oxford, OX3 0BP, United Kingdom.
authors.forename: Ammar H J
authors.initials: AH
authors.lastname: Al-Mayah
authors.forename: Sarah L
authors.initials: SL
authors.lastname: Irons
authors.forename: Ryan C
authors.initials: RC
authors.lastname: Pink
authors.forename: David R F
authors.initials: DR
authors.lastname: Carter
authors.forename: Munira A
authors.initials: MA
authors.lastname: Kadhim
mesh_terms: D000230:Adenocarcinoma / Q000473:pathology; D001943:Breast Neoplasms / Q000473:pathology; D024201:Bystander Effect / Q000502:physiology*; D045744:Cell Line, Tumor / Q000528:radiation effects / Q000648:ultrastructure; D019457:Chromosome Breakage; D002877:Chromosomes, Human / Q000528:radiation effects*; D020552:Comet Assay; D017077:Culture Media, Conditioned; D004249:DNA Damage; D004847:Epithelial Cells / Q000528:radiation effects / Q000648:ultrastructure; D055354:Exosomes / Q000737:chemistry / Q000502:physiology*; D005260:Female; D005720:Gamma Rays / Q000009:adverse effects*; D042822:Genomic Instability; D006801:Humans; D008854:Microscopy, Electron; D012313:RNA / Q000235:genetics*; D012259:Ribonuclease, Pancreatic / Q000494:pharmacology; D014461:Ultracentrifugation
chemical_list: D017077:Culture Media, Conditioned; D012313:RNA; D012259:Ribonuclease, Pancreatic