Low-Dose Non-Targeted Effects and Mitochondrial Control

Non-targeted effects (NTE) have been generally regarded as a low-dose ionizing radiation (IR) phenomenon. Recently, regarding long distant abscopal also observed at high doses of IR) relevant to antitumor therapy. IR is inducing NTE involving intracellular and extracellular signaling, which may lead short-ranging bystander long-ranging signaling effects. Internal “spontaneous” cellular stress mostly due metabolic oxidative mitochondrial energy production (ATP) through phosphorylation and/or anaerobic pathways accompanied by the leakage O2− other radicals from mitochondria during normal or increased requirements dysfunction. Among external stressors, has shown very rapidly perturb functions, leading supply demands ROS/NOS production. Depending on dose, this affects all types cell constituents, including DNA, RNA, amino acids, proteins, membranes, perturbing inner organization function, forcing cells reorganize metabolism network organelles. The reorganization implies cytoplasmic-nuclear shuttling important activation autophagy, mitophagy, well induction cycle arrest, DNA repair, apoptosis, senescence. It includes reprogramming genetic epigenetic control expression genes proteins in order ensure tissue survival. At low IR, directly irradiated already exert non-targeted release molecular mediators, such radicals, cytokines, fragments, small RNAs, (sometimes form vehicles exosomes), can induce damage unirradiated neighboring (abscopal) immune responses. Such are contributing phenomena, hormesis, adaptive responses, hypersensitivity, genomic instability, they promoting suppression cells. All these parts main defense systems tissues, IR-induced innate present review focused prominent role processes, determinants survival anti-tumor RT.