Cited by 710Effects of Radiation ExposureRedox biology and oxidative stressBioactive Compounds and Antitumor Agents

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

Spitz, Douglas R., Azzam, Edouard I., Jian Li, Jian, Gius, David·2004·Cancer and Metastasis Reviews

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.

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Crossref · 10.1023/b:canc.0000031769.14728.bc

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  • Generation of ROS is an important mediator of cellular alterations caused by radiation exposure, including mucositis.

    “The generation of ROS is also an important mediator of the cellular alterations caused by radiation exposure (Diehn et al., 2009; Sonis, 2009; Spitz et al., 2004), including mucositis (Citrin et al., 2010; Cotrim et al., 2007; Cotrim et al., 2005).”

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Authors
Spitz, D. R., Azzam, E. I., Jian Li, J., & Gius, D.
Affiliations
  • University of Iowa (US)
  • Rutgers New Jersey Medical School (US)
  • National Institutes of Health (US)
Corresponding author
Spitz, Douglas R.
Venue
Cancer and Metastasis Reviews
Published
2004-08
Volume
23
Issue
3-4
Pages
311-322
ISSN
  • 0167-7659 (ISSN-L)
  • 1573-7233
OpenAlex
W2023627397
Cited by
710
References
105
Citations by year
2026: 19 · 2025: 24 · 2024: 21 · 2023: 33 · 2022: 27 · 2021: 41 · 2020: 47 · 2019: 46 · 2018: 50 · 2017: 41 · 2016: 38 · 2015: 21 · 2014: 33 · 2013: 47 · 2012: 43
FWCI
2.51
Type
journal article
Language
en
Open access
closed
Locations
  • Cancer and Metastasis Reviews (publishedVersion)
  • PubMed (publishedVersion)
  • Rutgers University Community Repository (Rutgers University) (submittedVersion)
Topics
  • Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Effects of Radiation Exposure
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Toxicology › Bioactive Compounds and Antitumor Agents
Keywords
ionizing radiation, redox signaling, free radicals, radiation-induced oxidative damage, radiation adaptive response, bystander effect, cell cycle disruption, radiosensitization, genomic instability, inflammation, fibrosis, transcription factor activation, gene expression
MeSH terms
Animals, Cell Communication, Humans, Oxidation-Reduction, Radiation, Ionizing, Signal Transduction, Oxidative Stress, Genomic Instability

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