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

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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

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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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Ujowundu, C. O., Oyarebu, A. O., Nwaogu, L., & Ujowundu, F. N. (2018) · Biochemistry & Molecular Biology Journal · doi:10.21767/2471-8084.100070 · Cited by 11
“This is so because the free radicals provoke tissue injury by interacting with polyunsaturated fatty acids of phospholipids membranes [51,52] of hepatocytes and cell organelles producing free radicals and MDA.”
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Investigation of Biochemical Alterations in Ischemic Stroke Using Fourier Transform Infrared Imaging Spectroscopy—A Preliminary Study
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Mitochondrial base excision repair pathway failed to respond to status epilepticus induced by pilocarpine
Lin, Y. H., Xu, J., Cao, L., Han, Y., Gao, J., Xie, N., Zhao, X., Jiang, H., & Chi, Z. (2010) · Neuroscience Letters · doi:10.1016/j.neulet.2010.02.065 · Cited by 11
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Martino, N. A., Vicenti, R., Macciocca, M., Seracchioli, R., Marzano, G., Mastrorocco, A., Lacalandra, G. M., Tomaiuolo, M., Marchesani, G., Chiaravalle, E., et al. (2021) · PLoS ONE · doi:10.1371/journal.pone.0253536 · Cited by 10
“Studies in different cell types support facts that about one-third of the detrimental effects of ionizing radiation at the cellular level are due to direct DNA damage and two-thirds due to generation of reactive oxygen species (ROS) from ionization of water [71,72].”
Background
Nanotechnology meets radiobiology: Fullerenols and Metallofullerenols as nano-shields in radiotherapy
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4-(4-Hydroxy-3-methoxyphenyl)-2-butanone modulates redox signal in gamma-irradiation-induced nephrotoxicity in rats
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“ders and dysfunction of cells and tissues [1,2].”
Background
Exogenously-added copper/zinc superoxide dismutase rescues damage of endothelial cells from lethal irradiation
Tominaga, T., Hachiya, M., Shibata, T., SAKAMOTO, Y., Taki, K., & Akashi, M. (2011) · Journal of Clinical Biochemistry and Nutrition · doi:10.3164/jcbn.11-15 · Cited by 9
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“Concentrations of endogenous antioxidants, such as GSH, are reduced significantly in patients with inflammatory bowel disease and in experimental models of colitis [35, 36], and it has also been reported that glutathione supplementation can reduce the severity of oxidative damage in TNBS colitis [37, 38].”
Background
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Xu, X., Tan, Y., Mao, H., Liu, H., Dong, X., & Yin, Z. (2020) · Genes · doi:10.3390/genes11040349 · Cited by 10
“The oxidation-reduction reaction has been shown to play an important role in maintaining the normal mechanism of cellular signaling [36].”
Background
Gamma‐irradiation‐induced testicular oxidative stress and apoptosis: Mitigation by l ‐carnitine
Soliman, M. M., El-Shazly, S. A., & Aldhahrani, A. (2020) · Journal of Biochemical and Molecular Toxicology · doi:10.1002/jbt.22565 · Cited by 10
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The potential treatment of N-acetylcysteine as an antioxidant in the radiation-induced heart disease
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Etoricoxib–NLC Mitigates Radiation-Induced Ovarian Damage in Rats: Insights into Pro-Inflammatory Cytokines, Antioxidant Activity, and Hormonal Responses
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“However, radiation mostly damages the production of ROS, and increased ROS leads the ovaries to lose primordial follicles rapidly [30,31].”
On the Benefit of Cinnamomum zeylanicum for Radiology Unit Staff
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Radioprotective Effect of Zinc Nanoparticles on Ionizing Radiation-induced Nephrotoxicity in Mice
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The influence of redox status on inter-individual variability in the response of human peripheral blood lymphocytes to ionizing radiation
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“Together, these radiation effects initiate a series of biochemical and molecular signaling events that may result in reparable damage or in permanent physiological alterations which lead to cell death (Spitz et al. 2004).”
Background
Intercellular Communication in Response to Radiation Induced Stress: Bystander Effects in Vitro and in Vivo and Their Possible Clinical Implications
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“Irradiation leads to disturbances of the balance between pro-oxidant and anti-oxidant signaling molecules; one of such molecules can be nitric oxide (NO) (Spitz et al., 2004).”
Background
Particle Radiation-Induced Nontargeted Effects in Bone-Marrow-Derived Endothelial Progenitor Cells
Sasi, S. P., Park, D. S., Muralidharan, S., Wage, J., Kiladjian, A., Onufrak, J., Enderling, H., Yan, X., & Goukassian, D. A. (2015) · Stem Cells International · doi:10.1155/2015/496512 · Cited by 8
Radioprotective effect and other biological benefits associated with flavonoids
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Different responses of normal cells (red blood cells) and cancer cells (K562 and K562/Dox cells) to low-dose 137Cs gamma‑rays
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“…of x-ray ionization events in the cell medium, and the higher rates after a few minutes of radiation includes contributions from both the immediate products of radiolysis and the activation of cellular mechanisms that produce their own reactive oxygen species (Leach et al. 2001; Spitz et al. 2004).”
Background
Protective Role of Juniperus phoenicea L. Leaves Extract against Gamma-irradiation-induced Oxidative Stress
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“In between there is also radiationinduced free radical production, which can result in longterm responses [43].”
Background
Polyene phosphatidylcholine protects against radiation induced tissue injury without affecting radiotherapeutic efficacy in lung cancer.
Zhang, H., Jiang, T., Yu, H., Lu, H., Zhao, Y., Zhang, Y., Fu, J., Chen, W., Dong, P., Zang, L., et al. (2019) · PubMed Central · Cited by 8
Erratum to: Synergistic effect of aluminum and ionizing radiation upon ultrastructure, oxidative stress and apoptotic alterations in Paneth cells of rat intestine
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“Experimental studies have shown increased intracellular ROS levels and peroxide production following radiation exposure which has also been linked to tissue damage [60,61], and a correlation between IR induced oxidative stress and cardiotoxicity [60–62].”
Ameliorative Effect of Salicin Against Gamma Irradiation Induced Electrophoretic Changes in Brain Tissue in Male Rats
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“Ionizing radiation initiates a chain of biochemical and molecular changes that may repair the damage or culminate in permanent physiological changes.(5) Dose assessment or screening can play an important role in the epidemiological study of radiation exposure.”
Background
Lasting Effects of Low to Non-Lethal Radiation Exposure during Late Gestation on Offspring’s Cardiac Metabolism and Oxidative Stress
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“Oxidative stress has a critical role in the progression of radiation-induced injuries [55] There is little information, however, regarding the role of non-classical antioxidants in bone repair, but some proof-of-principle information has been obtained with standard antioxidants.”
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Background
Immunization and challenge shown by hamsters infected withOpisthorchis viverrinifollowing exposure to gamma-irradiated metacercariae of this carcinogenic liver fluke
Papatpremsiri, A., Junpue, P., Loukas, A. C., Brindley, P. J., Bethony, J. M., Sripa, B., & Laha, T. (2014) · Journal of Helminthology · doi:10.1017/s0022149x14000741 · Cited by 7
“The energy from ionizing radiation, such as g-rays, X-rays and ultraviolet (UV) light, damages cellular nucleic acids, proteins and lipids, leading to physiological changes or cell death (Spitz et al., 2004).”
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Puukila, S., Thome, C., Brooks, A. L., Woloschak, G. E., & Boreham, D. R. (2018) · International Journal of Radiation Biology · doi:10.1080/09553002.2018.1511929 · Cited by 7
“However, at low dose exposure to external sources of radiation, such as c rays, the change in ROS status may be protective (de Toledo et al. 2006; Spitz et al. 2004).”
Background
Radiation and oxidative stress
Koç, U., & Çam, İ. (2020) · Elsevier eBooks · doi:10.1016/b978-0-12-819092-0.00024-8 · Cited by 7
Oxidative Metabolism Involved in Non-targeted Effects Induced by Proton Radiation in Intact Arabidopsis Seeds
Tao, M. E. I., Yang, G., Quan, Y., Wang, W., Zhang, W., Xue, J., Wu, L., Gu, H., Schettino, G., & Wang, Y. (2011) · Journal of Radiation Research · doi:10.1269/jrr.10087 · Cited by 7
Pharmacological ascorbate combined with rucosopasem selectively radio-chemo-sensitizes NSCLC via generation of H2O2
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Toxicity of Radiation
Ray, K. (2017) · Elsevier eBooks · doi:10.1016/b978-0-12-804239-7.00020-2 · Cited by 6
Synthesis of nano-Fe3O4/ZnO composites with enhanced antibacterial properties and plant growth promotion via one-pot reaction
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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.
ORCID: Spitz, Douglas R.
Azzam, Edouard I.
Gius, David
Venue: Cancer and Metastasis Reviews
Publisher: Springer Science and Business Media LLC
Published: 2004-08
Volume: 23
Issue: 3-4
Pages: 311-322
ISSN: 0167-7659 (ISSN-L)
1573-7233
DOI: 10.1023/b:canc.0000031769.14728.bc
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
Licence: www.springernature.com/gp/researchers/text-and-data-mining (tdm)
www.springernature.com/gp/researchers/text-and-data-mining (vor)
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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Metabolic oxidation/reduction reactions and cellular responses to ionizing radiation: A unifying concept in stress response biology

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