A CCL2-based mechanism has been also suggested for other cases of stresses i.e., exposure to IR. Specifically, it was shown that a single-dose whole-body γ-irradiation (8 Gy) induced DNA damage in mice neuronal retina, which was complemented by a low-grade chronic inflammation, para-inflammation, characterized by upregulated expression of chemokines (CCL2, CXCL12, and CX3CL1) and microglial activation . Recent patient studies also suggest an actual involvement of cytokines in the induction of RT-induced systemic DNA damage in normal tissues distant to the irradiation site . More specifically in this study, sixteen patients with non-small cell lung carcinoma (NSCLC) received 60 Gy in 30 fractions of definitive thoracic RT with or without concurrent chemotherapy (chemoRT) and peripheral blood lymphocytes (PBL) and eyebrow hairs samples were taken prior, during, and after RT. The results showed an elevation of DSBs manifested as γH2AX foci in PBL, representing normal tissues in the irradiated thorax volume, 1 hour after fraction one and γH2AX foci numbers returned to near baseline values in 24 hours after treatment. Most importantly, unirradiated hair follicles, exhibited delayed systemic (abscopal) DDR measured as γH2AX foci which increased at 24 hours post-fraction one, and remained elevated during treatment in a dose-independent manner. This distant radiation effect was related with changes in plasma levels of MDC/CCL22 and MIP-1α/CCL3 cytokines. Interestingly and consistent with the unifying model suggestion introduced by Georgakilas uniting different types of stress i.e., radiations and a growing tumor , MCP-1 blockade by neutralizing antibodies was found to inhibit lung cancer tumor growth by altering macrophage phenotype and activating cytotoxic CD8+ T lymphocytes (CTLs) . Another side of the same coin of cytokines-inflammation is the reverse activity. Earlier studies have shown that ROS/RNS could be generated in vitro by a mixture of inflammatory cytokines (IL-1β, IFN-γ and tumor necrosis factor α) in three human cholangiocarcinoma cell lines by a nitric oxide (NO)-dependent response, as assessed by alkaline (denaturing) comet assay . In addition, a parallel inhibition of global DNA repair activity by 70% was detected. These and later data indicate that activation of iNOS and excess production of NO in response to inflammatory cytokines can cause DNA damage and inhibit DNA repair, at least partially. Recent extensive bioinformatics-based metanalysis studies have verified the interactions between mediators of systemic effects and DDR/R components, as well as interactions between pattern recognition receptors (PRPs) and DNA repair proteins like BRCA1, XRCC1, DNA-PK, Ku70/80 and others . Recently, Nikitaki et al. produced a detailed list of proteins implicated in different categories of radiation-induced systemic effects, including the clinically relevant abscopal phenomenon, using improved text-mining and bioinformatics tools from the literature. Genes belonging to the DDR/R pathway and protein-protein interaction (PPi) networks as well as KEGG pathway analyses have revealed that the main pathways participating in NTE are: apoptosis, TLR-like and NOD-like receptor signaling pathways .