Adaptive and Pathological Outcomes of Radiation Stress-Induced Redox Signaling

Significance: Ionizing radiation can damage cells either directly or through oxidative damage caused by ionization. Although radiation exposure from natural sources is very limited, ionizing radiation in nuclear disaster zones and long spaceflights causes inconspicuous, yet measurable physiological effects in men and animals, whose significance remains poorly known. Understanding the physiological impacts of ionizing radiation has a wide importance due to the increased use of medical imaging and radiotherapy.Recent Advances: Radiation exposure has been traditionally investigated from the perspective of DNA damage and its consequences. However, recent studies from Chernobyl as well as spaceflights have provided interesting insights into oxidative stress-induced metabolic alterations and disturbances in the circadian regulation.Critical Issues: In this review, we discuss the physiological consequences of radiation exposure in the light of oxidative stress signaling. Radiation exposure likely triggers many converging or interconnecting signaling pathways, some of which mimic mitochondrial dysfunction and might explain the observed metabolic changes.Future Directions: Better understanding of the different radiation-induced signaling pathways might help to devise strategies for mitigation of the long-term effects of radiation exposure. The utility of fibroblast growth factor 21 (FGF21) as a radiation exposure biomarker and the use of radiation hormesis as a method to protect astronauts on a prolonged spaceflight, such as a mission to Mars, should be investigated.