title: Oxidative damage pathways in relation to normal tissue injury.
abstract: Given the increasing population of long-term cancer survivors, the need to mitigate or treat late effects has emerged as a primary area of radiation biology research. Once thought to be irreversible, radiation-induced late effects are now viewed as dynamic multicellular interactions between multiple cell types within a particular program that can be modulated. The molecular, cellular and biochemical pathways responsible for radiation-induced late morbidity remain ill-defined. This review provides data in support of the hypothesis that these late effects are driven, in part, by a chronic oxidative stress. Irradiating late responding normal tissues leads to chronic increases in reactive oxygen/reactive nitrogen oxide species that serve as intracellular signaling species to alter cell function/phenotype, resulting in chronic inflammation, organ dysfunction, and ultimate fibrosis and/or necrosis. Furthermore, we hypothesize that the effectiveness of renin-angiotensin system blockers in preventing or mitigating the severity of radiation-induced late effects reflects, in part, inhibition of reactive oxygen species generation and the resultant chronic oxidative stress. These findings provide a robust rationale for anti-inflammatory-based interventional therapies in the treatment of late normal tissue injury.
authors: Department of Radiation Oncology, Brain Tumor Center of Excellence, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA.
authors: W
authors: W
authors: Zhao
authors: D I
authors: DI
authors: Diz
authors: M E
authors: ME
authors: Robbins
mesh_terms: D000804:Angiotensin II / Q000502:physiology; D000818:Animals; D006801:Humans; D007249:Inflammation / Q000209:etiology; D018384:Oxidative Stress / Q000528:radiation effects*; D011832:Radiation Injuries / Q000503:physiopathology* / Q000628:therapy; D026361:Reactive Nitrogen Species / Q000502:physiology; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000528:radiation effects
chemical_list: D026361:Reactive Nitrogen Species; D017382:Reactive Oxygen Species; D000804:Angiotensin II