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Oxidative DNA damage caused by inflammation may link to stress-induced non-targeted effects - PubMed

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Oxidative DNA damage caused by inflammation may link to stress-induced non-targeted effects

Carl N Sprung et al. Cancer Lett. 2015.

Abstract

A spectrum of radiation-induced non-targeted effects has been reported during the last two decades since Nagasawa and Little first described a phenomenon in cultured cells that was later called the "bystander effect". These non-targeted effects include radiotherapy-related abscopal effects, where changes in organs or tissues occur distant from the irradiated region. The spectrum of non-targeted effects continue to broaden over time and now embrace many types of exogenous and endogenous stressors that induce a systemic genotoxic response including a widely studied tumor microenvironment. Here we discuss processes and factors leading to DNA damage induction in non-targeted cells and tissues and highlight similarities in the regulation of systemic effects caused by different stressors.

Keywords: Abscopal effects; Bystander effect; DNA damage; Ionizing radiation; Non-targeted effects; Radiation induced bystander effects.

Crown Copyright © 2013. Published by Elsevier Ireland Ltd. All rights reserved.

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Figures

Figure 1
Figure 1. Exposure to genotoxic stress and the presence of a tumor lead to similar responses that affect both adjacent and distant tissues

Both genotoxic stress such as ionizing radiation, ultraviolet radiation, cancer drugs or the presence of a tumor can lead to the production of cytokines and reactive species such as ROS, RNS and NO, which can disseminate into surrounding cells via diffusion or gap junctions, leading to alterations in cell metabolism (changes in protein and miRNA expression) and DNA damage. In turn, persistent DNA damage can lead to genomic instability (mutations, chromosome aberrations, micronuclei), senescence, or ultimately to cell transformation. These types of local responses can persistently produce an inflammatory response. Both activated immune cells (such as macrophages and neutrophils) and long-lived reactive species can circulate to distant tissues and produce additional cytokines and reactive species to further activate macrophages and/or other immune cells to produce DNA damage, apoptosis, micronuclei, senescence, cell transformation, etc. in distant tissues. TAM: Tumor-associated macrophage, MN: Micronucleus.

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