Radiation-induced non-targeted effects: some open questions

Abstract

The existence of non-targeted effects (NTEs) of radiation (genomic instability and bystander effects) has been generally accepted for >20 y; however, there is research, which was largely ignored going back to 1915 reporting these effects. Despite today's general acceptance of the phenomenon of NTE, there is little agreement about the mechanisms involved and the implications in radiation biology and radiation protection. The aim of this review was to consider some of the odd data, which have been published in the field with a view to obtaining insights or stimulating new ways of thinking about this field. By highlighting some key challenges and controversies, concerning the mechanisms and more importantly, the reason these effects exist, current ideas about the wider implications of NTEs in evolution and biology are also discussed.

Radiation-Induced Bystander Effect is Mediated by Mitochondrial DNA in Exosome-Like Vesicles

“…RIBE has been detected in vitro 3–6 , in 3D tissues 7 , and in mouse models 8–10 . Growing evidence shows that bystander responses can be regulated by two mechanisms—(i) gap junction intercellular communication (ii) communication of soluble factors released by irradiated cells or organs 11,12 . With respect to the soluble factors, Mothersill and Seymour first reported that the irradiated medium from human epithelial cell medium displayed a toxic effect on fibroblast cells 13 .…”

Biological Entanglement–Like Effect After Communication of Fish Prior to X-Ray Exposure

“…Most researchers agree that reactive oxygen and/or nitrogen species are involved and that p53, cytokines, and stress response pathways such as Mitogen activated protein kinase (MAPK) are important. 13 – 15 Ion channels in both outer cell membranes and mitochondrial membranes appear to be involved. 16 – 19 More recently, a role of UV resulting from both excitation decay and exosomes has been identified, 20 – 23 and these are thought to contain miRNAs, although exosome profiling is at a very early stage.…”

Microarray Profiling of TGF-β1-Induced Long Non-Coding RNA Expression Patterns in Human Lung Bronchial Epithelial BEAS-2B Cells

“…Extensive researches have focused on the health effects of IR in the hope of understanding the risk of IR exposure. In contrast to the traditional radiobiological viewpoint that the biological effects of IR are restricted to directly hit cells, the concept of radiation-induced bystander effects (RIBE) has updated our perception of the biological effects of IR [2]. It is realized that the existing radiotherapy models should be reconsidered due to the discovery of radiation-induced secondary carcinogenesis in distant organs after radiotherapy [3], as well as the carcinogenesis induced by low-dose/low-dose-rate (LD/LDR) radiations, for example, the astronauts exposed to LD/ LDR high atomic number (Z) and energy (HZE) space radiations [4].…”

“…It is realized that the existing radiotherapy models should be reconsidered due to the discovery of radiation-induced secondary carcinogenesis in distant organs after radiotherapy [3], as well as the carcinogenesis induced by low-dose/low-dose-rate (LD/LDR) radiations, for example, the astronauts exposed to LD/ LDR high atomic number (Z) and energy (HZE) space radiations [4]. It is generally believed that both gap junctional intercellular communication (GJIC) and soluble factors generated by the irradiated cells are involved in the RIBE [2], of which transforming growth factor-β1 (TGF-β1) is a key soluble factors [5][6][7]. Although TGF-β1-related signaling pathways were studied extensively, the mechanisms underlying the TGF-β1-induced tumorigenesis remain unclear, especially its role in LD/LDR radiations-or RIBE-induced tumorigenesis.…”