Mechanisms of Radiation Bystander and Non-Targeted Effects: Implications to Radiation Carcinogenesis and Radiotherapy

摘要

Background: Knowledge of radiobiology is of paramount importance to be able to grasp andhave an in-depth understanding of the consequences of ionizing radiation. One of the most importanteffects of this physical stressor’s interaction to targeted and non-targeted cells, tissues and organs is onthe late effects on the development of primary and secondary cancers. Thus, an in-depth understandingof the mechanisms of radiation carcinogenesis remains to be elucidated, and some studies have demonstratedor proposed a role of non-targeted effect in excess risk of cancer incidence. The non-targetedeffect in radiobiology refers to a dynamic complex response in non-irradiated tissues caused by the releaseof presumably of clastogenic factors from irradiated cells. Although, most of these responses innon-targeted tissues have marked similarities to irradiated tissues, other studies have shown some differences.Also, the non-targeted effect has shown sex and tissue specificity that are seen in irradiatedtissues too. So far, several studies have been conducted to depict mechanisms that may be involved inthis phenomenon. Epigenetic dysfunctions, DNA damage and cell death are responsible for initiation ofseveral signaling pathways that finally result in secretion of clastogenic factors. Moreover, studies haveshown that damage to both nucleus and mitochondrial DNA, membrane and some organelles is involved.Oxidized DNA associated with other cell death factors stimulates secretion of inflammatory aswell as some anti-inflammatory cytokines from irradiated area. Additionally, oxidative stress that resultsin damage to cellular structures to include cell membranes can affect secretion of exosomes and miRNAs.These bystander effect exogenous mediators migrate to distant tissues and stimulate various signalingpathways which can lead to changes in immune responses, epigenetic modulations and radiationcarcinogenesis.Conclusion: In this review, we focus on descriptive and hierarchical events with emphasis on the molecularand functional interactions of ionizing radiation with cells to the mechanisms involved in cancerinduction in non-targeted tissues.