Oxidative damage pathways in relation to normal tissue injury
- 1 September 2007
- journal article
- review article
- Published by Oxford University Press (OUP) in The British Journal of Radiology
- Vol. 80 (special__1), S23-S31
- https://doi.org/10.1259/bjr/18237646
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.Keywords
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