Metabolic oxidation/reduction reactions and cellular responses to ionizing radiation: A unifying concept in stress response biology

Abstract

Exposure of eukaryotic cells to ionizing radiation (IR) results in the immediate formation of free radicals that last a matter of milliseconds. It has been assumed that the subsequent alterations in multiple intracellular processes following irradiation is due to the initial oxidative damage caused by these free radicals. However, it is becoming increasingly clear that intracellular metabolic oxidation/reduction (redox) reactions can be affected by this initial IR-induced free radical insult and may remain perturbed for minutes, hours, or days. It would seem logical that these cellular redox reactions might contribute to the activation of protective or damaging processes that could impact upon the damaging effects of IR. These processes include redox sensitive signaling pathways, transcription factor activation, gene expression, and metabolic activities that govern the formation of intracellular oxidants and reductants. The physiological manifestations of these radiation-induced alterations in redox sensitive processes have been suggested to contribute to adaptive responses, bystander effects, cell cycle perturbations, cytotoxicity, heat-induced radiosensitization, genomic instability, inflammation, and fibrosis. While a great deal is known about the molecular changes associated with the initial production of free radicals at the time of irradiation, the contribution of perturbations in redox sensitive metabolic processes to biological outcomes following exposure to IR is only recently becoming established. This review will focus on evidence supporting the concept that perturbations in intracellular metabolic oxidation/reduction reactions contribute to the biological effects of radiation exposure as well as new concepts emerging from the field of free radical biology that may be relevant to future studies in radiobiology.

Increased frequency of chromosomal aberrations and sister chromatid exchanges in peripheral lymphocytes of radiology technicians chronically exposed to low levels of ionizing radiations

“…Although in many hospital radiology units the radiation exposure remains below these levels, there is a higher risk for hospital workers handling diagnostic X-ray machines and γ-cameras due to the chronic but cumulative exposure to low doses of IR. One consequence of the exposure to IR is the formation of free radicals, such as peroxynitrites and hydroxyl radicals (Zhang et al, 2000;Spitz et al, 2004), able to produce some important alterations in the living cells. At DNA level, IR exerts its genotoxic effect by the induction of singleand double-strand breaks, a-basic sites and oxidized bases.…”

Low dose radiation response curves, networks and pathways in human lymphoblastoid cells exposed from 1 to 10cGy of acute gamma radiation

“…These studies demonstrate that doses of 1 cGy of low-linear energy transfer (LET) radiation (~0.3 double strand breaks per cell) are sufficient to modulate gene expression. However, there is insufficient information on the shape and slope of the low dose response curves for gene expression and the associated molecular functions, both of which are needed to assess relevance of the LNT model [43].…”

Integrated Bioinformatics for Radiation-Induced Pathway Analysis from Proteomics and Microarray Data

“…Radiation induces a myriad of cellular responses, including genotoxic stress signaling, cell cycle arrest, activation of a complex DNA repair machinery, and metabolic changes (Valerie, et al, 2007;Jeggo and Löbrich 2006;Spitz et al, 2004). ATM, or ataxia-telangiectasia mutated was first identified in AT patients in 1995 (Savitsky et al, 1995).…”