Radiation-induced bystander signalling in cancer therapy

Abstract

Our understanding of how radiation kills normal and tumour cells has been based on an intimate knowledge of the direct induction of DNA damage and its cellular consequences. What has become clear is that, as well as responses to direct DNA damage, cell–cell signalling — known as the bystander effect — mediated through gap junctions and inflammatory responses may have an important role in the response of cells and tissues to radiation exposure and also chemotherapy agents. This Review outlines the key aspects of radiation-induced intercellular signalling and assesses its relevance for existing and future radiation-based therapies.

Preferential induction of apoptotic cell death in melanoma cells as compared with normal keratinocytes using a non-thermal plasma torch

“…The bystander effect is the promotion of cell death through the passage of apoptosisinducing signals through gap junctions which has previously been reported under various conditions. 20 The WM793B and 1205Lu melanoma cells were transfected with wild type (Cx43) or a dominant negative Cx43 (T154A). 27 Following two rounds of selection, we obtained 100% GFP expressing cells as shown in 1D.…”

“…19 The "bystander effect" is the promotion of cell death through the passage of apoptosis-inducing signals through gap junctions. 20 The bystander effect has been reported for UV radiation, 21 photodynamic therapy, 22 heat, 23 chemotherapy agents 24 and radiation. 20 In this report we demonstrate that gap junctions may also play a role in promoting cell death in melanoma cells by NTP.…”

Bystander Signalling: Exploring Clinical Relevance Through New Approaches and New Models

“…A number of candidate signalling molecules have been identified in mediating RIBEs such as reactive oxygen and nitrogen species (ROS/NOS) including nitric oxide (NO), and cytokines such as transforming growth factor-β (TGF-β) and interleukin-8 (IL-8). These have been shown to initiate multiple downstream signalling pathways including the mitogen activated protein kinases (MAPKs) and nuclear factor-κB (NF-κB) pathways (8).…”

Role of oxidatively-induced DNA damage and inflammation in radiation long term effects and carcinogenesis

“…Increased production of reactive oxygen and nitrogen species (ROS/RNS), which usually leads to lipid peroxidation, oxidation injury of proteins and DNA, as well as release of pro-inflammatory and/or various clastogenic (chromosome breaking) factors (tumor necrosis factor, free radicals, lipid peroxidation byproducts, inosine triphosphate and others) has been observed in vitro and in vivo. In the past ten years, evidence has accumulated for a novel biological phenomenon termed as "radiation-induced bystander effect" (RIBE) (discussed also above), wherein directly irradiated cells transmit "damaging" signals like soluble plasma clastogenic factors to non-irradiated cells and neighboring tissues thereby inducing a DNA damage response very similar to that of irradiated cells [9] . The in vivo though confirmation of the 'bystander' phenomenon is needed in order to eliminate uncertainties in the field of radiation therapy and biology and to provide a solid foundation for assessing the possible implications of this effect in humans exposed to ionizing radiations.…”