Possible Role of Exosomes Containing RNA in Mediating Nontargeted Effect of Ionizing Radiation

TLDR

The bystander effect, where irradiated cells induce damage in un‑irradiated neighbors, can cause chromosomal instability in progeny, but the mediating factors—potentially transferred via gap junctions or extracellular release—remain poorly defined. The study tested whether an RNA‑containing exosome mediates the bystander effect. MCF7 cells were exposed to 2 Gy X‑rays, and their conditioned media were collected for analysis. RNase treatment eliminated the media’s ability to cause chromosomal damage, while exosomes isolated from the media increased genomic damage, indicating that exosome‑carried RNA contributes to the bystander effect and genomic instability.

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.