Changes in gene expression as one of the key mechanisms involved in radiation-induced bystander effect

The radiation-induced bystander effect (RIBE) refers to the manifestation of responses by non-targeted/non-hit cells or tissues situated in proximity to cells and tissues directly exposed to ionizing radiation (IR). The RIBE is elicited by agents and factors released by IR-hit cells. The growing body of data suggests that the underlying mechanisms of the RIBE are multifaceted depending both on the biological (characteristics of directly IR-exposed cells, bystander cells, intercellular milieu) and the physical (dose, rate and type of IR, time after exposure) factors/parameters. Although the exact identity of bystander signal(s) is yet to be identified, the published data indicate changes in gene expression for multiple types of RNA (mRNA, microRNA, mitochondrial RNA, long non-coding RNA, small nucleolar RNA) as being one of the major responses of cells and tissues in the context of the RIBE. Gene expression profiles demonstrate a high degree of variability between distinct bystander cell and tissue types. These alterations could independently, or in a signaling cascade, result in the manifestation of readily observable endpoints, including changes in viability and genomic instability. Here, the relevant publications on the gene candidates and signaling pathways involved in the RIBE are reviewed, and a framework for future studies, both in vitro and in vivo, on the genetic aspect of the RIBE is provided.