The DOI matches its Crossref record; 105 of the 105 references it cites were found in a registry or an index.
Metabolic oxidation/reduction reactions and cellular responses to ionizing radiation: A unifying concept in stress response biology
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.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“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).”
From mTOR inhibition prevents epithelial stem cell senescence and protects from radiation-induced mucositis (2012) · cites this paper as Spitz et al., 2004
Citations
Cites
Free radicals in biology and medicine
Gutteridge, J. M. C. (1991) · General Pharmacology The Vascular System · doi:10.1016/0306-3623(91)90478-o · Cited by 17,178
Oxidants, oxidative stress and the biology of ageing
Finkel, T., & Holbrook, N. J. (2000) · Nature · doi:10.1038/35041687 · Cited by 9,413
Aging: a theory based on free radical and radiation chemistry
Harman, D. (1956) · Journal of Gerontology · doi:10.1093/geronj/11.3.298 · Cited by 8,567
Schafer, F. Q., & Buettner, G. R. (2001) · Free Radical Biology and Medicine · doi:10.1016/s0891-5849(01)00480-4 · Cited by 4,587
Oxidative stress: oxidants and antioxidants
Sies, H. (1997) · Experimental Physiology · doi:10.1113/expphysiol.1997.sp004024 · Cited by 4,577
Radiobiology for the Radiologist.
(1974) · Annals of Internal Medicine · doi:10.7326/0003-4819-80-3-438_1 · Cited by 3,498
Cell transformation by the superoxide-generating oxidase Mox1
Suh, Y.-A., Arnold, R. S., Lassegue, B., Shi, J., Xu, X., Sorescu, D., Chung, A. B., Griendling, K. K., & Lambeth, J. D. (1999) · Nature · doi:10.1038/43459 · Cited by 1,480
REDOX REGULATION OF CELLULAR ACTIVATION
Nakamura, H., Nakamura, K., & Yodoi, J. (1997) · Annual Review of Immunology · doi:10.1146/annurev.immunol.15.1.351 · Cited by 1,106
Oxygen poisoning and x-irradiation: a mechanism in common
Gerschman, R., Gilbert, D. L., Nye, S. W., Dwyer, P., & Fenn, W. O. (1954) · Science · doi:10.1126/science.119.3097.623 · Cited by 961
Wong, G. H. W., Elwell, J. H., Oberley, L. W., & Goeddel, D. V. (1989) · Cell · doi:10.1016/0092-8674(89)90944-6 · Cited by 802
Flagged first, then by citations
Research works printed but not linked: 9
- Altman KI, Gerber GB, Okada S: Radiation Biochemistry. Academic Press, New York, 1970
- Petkau A, Chelack WS, Pleskach SD: Protection of postirradiated mice by superoxide dismutase. Int J Radiat Biol 29: 297–299, 1976
- Lehninger AL: Lehninger Principals of Biochemistry. Worth Publishers Inc., New York, NY, 2000
- Boveris A, Cadenas E: Production of superoxide radicals and hydrogen peroxide in mitochondria. Superoxide Dismutase:Volume II, L.W. Oberley, ed. CRC Press Inc., Boca Raton, Florida, 1982
- Esterbauer HH, Zollner H, Schaur RJ: Aldehydes formed by lipid peroxidation: Mechanisms of formation, occurrence, and determination. Membrane Lipid Oxidation. CRC Press Inc., Boca Raton, Florida, pp. 240–268, 1990
- Yamamoto Y, Niki E: Role of antioxidants in lipid peroxidation. Membrane Lipid Oxidation. CRC Press Inc., Boca Raton, Florida, pp. 286-301
- Finkel T, Holbrook NJ: Oxidants, oxidative stress and the biology of aging. Nature 408(6809): 239–247, 2000 · DOI · Paper page
- Zhao W, Spitz DR, Oberley LW Robbins MEC: Redox modulation of the pro-fibrogenic mediator plasminogen activator inhibitor-1. Cancer Res 61: 5537–5543, 2001
- Buettner GR, Ng C, Oberley LW, Rodgers VG, Schafer FQ: Does MnSOD influence H2O2 production in mitochondria. Free Radic Biol Med 29(supplement 1): S21, 2000
Cited by
Sorted by citations
Items 201–300 of 708
Wang, Z., Cao, N., Nantajit, D., Fan, M., Liu, Y., & Li, J. J. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m802229200 · Cited by 47
Chen, X., & Kitts, D. D. (2011) · Journal of Agricultural and Food Chemistry · doi:10.1021/jf2031583 · Cited by 47
Domogauer, J., de Toledo, S. M., Howell, R. W., & Azzam, E. I. (2021) · Cell Communication and Signaling · doi:10.1186/s12964-021-00711-4 · Cited by 48
Oxidative stress in radiology staff
Malekırad, A. A., Ranjbar, A., Rahzani, K., Pilehvarian, A. A., Rezaie, A. R., Zamani, M. J., & Abdollahi, M. R. (2005) · Environmental Toxicology and Pharmacology · doi:10.1016/j.etap.2005.01.005 · Cited by 47
“sis, atrophy, vascular damage, and DNA breakage (Spitz et al., 2004).”
BackgroundCortés, M. M., Giedzinski, E., Limoli, C. L., & Luderer, U. (2009) · Mutagenesis · doi:10.1093/mutage/gen073 · Cited by 47
Beer, L., Seemann, R., Ristl, R., Ellinger, A., Kasiri, M. M., Mitterbauer, A., Zimmermann, M., Gabriel, C., Gyöngyösi, M., Klepetko, W., et al. (2014) · BMC Genomics · doi:10.1186/1471-2164-15-814 · Cited by 46
“Background Exposure of living cells to ionizing radiation (IR) results in the generation of free radicals and reactive oxygen species (ROS) [1].”
Veeraraghavan, J., Natarajan, M., Herman, T. S., & Aravindan, N. (2010) · Mutation Research/Genetic Toxicology and Environmental Mutagenesis · doi:10.1016/j.mrgentox.2010.10.006 · Cited by 46
Is Ionizing Radiation Harmful at any Exposure? An Echo That Continues to Vibrate
Azzam, E. I., Colangelo, N. W., Domogauer, J., Sharma, N., & de Toledo, S. M. (2016) · Health Physics · doi:10.1097/hp.0000000000000450 · Cited by 46
“Further, antioxidant defenses (enzymes that scavenge reactive oxygen species, proteases to remove oxidized molecules) act to neutralize the induced oxidative stress, which may also result in minimizing the mutagenic potential of the byproducts of normal oxidative metabolism (Spitz et al. 2004).”
BackgroundEpperly, M. W., Dixon, T. M., Wang, H., Schlesselman, J. J., Franicola, D., & Greenberger, J. S. (2008) · Radiation Research · doi:10.1667/rr1286.1 · Cited by 45
“in fractionated irradiation experiments is safe and effective and is associated with no further exacerbation of acute radiation effects (23, 24).”
BackgroundMechanistic Understanding of Lung Inflammation: Recent Advances and Emerging Techniques
Keskinidou, C., Vassiliou, A. G., Dimopoulou, I., Kotanidou, Α., & Orfanos, S. E. (2022) · Journal of Inflammation Research · doi:10.2147/jir.s282695 · Cited by 50
“The induced generation of free radicals impairs oxidative metabolism in the irradiated cells and neighboring cells, through cellular communication pathways.(206,207) Among the enzymes that are unregulated by ROS and RNS production are NADPH oxidases.”
BackgroundEfficacy of Glutamine in the Prevention of Acute Radiation Enteritis
Vidal‐Casariego, A., Calleja‐Fernández, A., de Urbina‐González, J. J. O., Cano‐Rodríguez, I., Cordido, F., & Ballesteros-Pomar, M. D. (2013) · Journal of Parenteral and Enteral Nutrition · doi:10.1177/0148607113478191 · Cited by 45
Prolyl-hydroxylase 3: evolving roles for an ancient signaling protein
Domann, F. E., & Place (2013) · Hypoxia · doi:10.2147/hp.s50091 · Cited by 45
“16 This O 2 − is dismutated to H 2 O 2 by manganese superoxide dismutase, and ultimately results in PHD inactivation by the mechanism described above (see Figure 3).”
Radiation hormesis: Autophagy and other cellular mechanisms
Szumiel, I. (2012) · International Journal of Radiation Biology · doi:10.3109/09553002.2012.699698 · Cited by 45
“Th e unifying concept of cellular oxidative stress was presented by Spitz et al. (2004).”
BackgroundGenotoxic stress accelerates age-associated degenerative changes in intervertebral discs
Nasto, L. A., Wang, D., Robinson, A. R., Clauson, C. L., Ngo, K., Dong, Q. D., Roughley, P. J., Epperly, M. W., Huq, S. M., Pola, E., et al. (2012) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2012.11.002 · Cited by 45
“This is in addition to the direct, physical DNA damage caused by ionizing or breaking DNA molecules, leading to single- and double-strand breaks (Spitz et al., 2004).”
Low-Dose Non-Targeted Effects and Mitochondrial Control
Averbeck, D. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms241411460 · Cited by 51
“The highly diffusible reactive oxygen or nitrogen species (ROS and NOS) are formed during metabolic activity and are involved in redox-regulated signaling, and they are second messengers in cell signaling and direct gene expression.”
BackgroundInfluentialBuonanno, M., de Toledo, S. M., & Azzam, E. I. (2011) · PLoS ONE · doi:10.1371/journal.pone.0021540 · Cited by 44
“The net effect is clustered damage in DNA and other molecules [5] that occur shortly after irradiation and can extend along a long column of cells in tissue [6], and perturbation of oxidative metabolism that results in delayed damage [7].”
BackgroundZou, X., Santa-Maria, C. A., O’Brien, J., Gius, D. R., & Zhu, Y. (2016) · Antioxidants and Redox Signaling · doi:10.1089/ars.2016.6641 · Cited by 44
“Electrons transferred through oxidative phosphorylation (OXPHOS) constitute a major way of ROS production since electrons can leak out of complexes I and III, resulting in one-electron reductions of oxygen to produce the superoxide radical (76).”
Very low doses of heavy oxygen ion radiation induce premature ovarian failure
Mishra, B., Ripperdan, R., Ortiz, L., & Luderer, U. (2017) · Reproduction · doi:10.1530/rep-17-0101 · Cited by 44
Redox Signaling via Lipid Peroxidation Regulates Retinal Progenitor Cell Differentiation
Albadri, S., Naso, F., Thauvin, M., Gauron, C., Parolin, C., Duroure, K., Vougny, J., Fiori, J., Boga, C., Vriz, S., et al. (2019) · Developmental Cell · doi:10.1016/j.devcel.2019.05.011 · Cited by 44
Hafer, K., Iwamoto, K. K., Scuric, Z., & Schiestl, R. H. (2007) · Radiation Research · doi:10.1667/rr0717.1 · Cited by 44
Cell Cycle Regulators Guide Mitochondrial Activity in Radiation-Induced Adaptive Response
Alexandrou, A. T., & Li, J. J. (2013) · Antioxidants and Redox Signaling · doi:10.1089/ars.2013.5684 · Cited by 42
“A topic on redox reactions in cellular responses to IR has been well reviewed (199).”
InfluentialBera, S., Greiner, S. M., Choudhury, A., Dispenzieri, A. A., Spitz, D. R., Russell, S. J., & Goel, A. (2010) · Neoplasia · doi:10.1593/neo.101146 · Cited by 42
“Dex is also an anti-inflammatory drug that inhibits the activation of the redox-regulated prosurvival transcription factors nuclear factor κB (NF-κB) and activator protein 1 (AP-1) that govern cellular radiosensitivity [25].”
BackgroundBowler, D. A., Moore, S. R., Macdonald, D. A., Smyth, S. H., Clapham, P., & Kadhim, M. A. (2006) · Mutation research. Fundamental and molecular mechanisms of mutagenesis · doi:10.1016/j.mrfmmm.2005.04.025 · Cited by 43
Ye, Q. (2012) · International Journal of Molecular Medicine · doi:10.3892/ijmm.2012.916 · Cited by 43
Olaku, O. O., Ojukwu, M., Zia, F. Z., & White, J. D. (2015) · Nutrition and Cancer · doi:10.1080/01635581.2015.1029639 · Cited by 42
“If this damage is irreparable, then injury, mutagenesis, carcinogenesis, accelerated senescence, and cell death can occur (12).”
BackgroundCharged iron particles, components of space radiation, destroy ovarian follicles
Mishra, B., Ortiz, L., & Luderer, U. (2016) · Human Reproduction · doi:10.1093/humrep/dew126 · Cited by 44
“…g-irradiation chronically elevates cellular reactive oxygen species (ROS) production and oxidative stress and that ROS initiate apoptotic death of ovarian follicles (Spitz et al., 2004; Tsai-Turton and Luderer, 2006; Tsai-Turton et al., 2007; Dayal et al., 2008; Cortés-Wanstreet et al., 2009).”
BackgroundInfluentialBanerjee, S., Aykin‐Burns, N., Krager, K. J., Shah, S. K., Melnyk, S. B., Hauer‐Jensen, M., & Pawar, S. A. (2016) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2016.08.022 · Cited by 43
“If cells are deficient in the production of antioxidants to scavenge IR-induced oxidative stress and/or are impaired in the repair of IR-induced DSBs, they could be more sensitive to IR-induced apoptosis or become genetically unstable if they survive the initial IR insult [10,14].”
BackgroundMaremonti, E., Eide, D. M., Rossbach, L. M., Lind, O. C., Salbu, B., & Brede, D. A. (2019) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2019.11.037 · Cited by 43
Brown, C. O., Schibler, J., Fitzgerald, M. P., Singh, N., Salem, K., Zhan, F., & Goel, A. (2013) · Leukemia Research · doi:10.1016/j.leukres.2013.03.004 · Cited by 43
“Studies have shown that persistent high-levels of oxidative stress can lead to adverse events such as oncogene activation and genomic instability culminating in cancer progression and therapy resistance [10,11].”
BackgroundMostafa, N. M., Edmond, M. P., El‐Shazly, M., Fahmy, H. A., Sherif, N. H., & Singab, A. N. B. (2021) · Natural Product Research · doi:10.1080/14786419.2021.1961252 · Cited by 42
“In addition, it possesses anti-inflammatory and antioxidant activities (Tanna et al. 2009; Sashidhara et al. 2011).”
BackgroundKandhare, A. D., Kumar, V. S., Adil, M., Rajmane, A. R., Ghosh, P., & Bodhankar, S. L. (2012) · Oriental Pharmacy and Experimental Medicine · doi:10.1007/s13596-012-0090-2 · Cited by 42
Exercise training enhances the skeletal muscle response to radiation‐induced oxidative stress
Lisio, M. D., Kaczor, J. J., Phan, N., Tarnopolsky, M. A., Boreham, D. R., & Parise, G. (2010) · Muscle & Nerve · doi:10.1002/mus.21797 · Cited by 42
Radiation-Induced Delayed Bystander-Type Effects Mediated by Hemopoietic Cells
Burr, K., Robinson, J. I., Rastogi, S., Boylan, M. T., Coates, P. J., Lorimore, S. A., & Wright, E. G. (2010) · Radiation Research · doi:10.1667/rr1937.1 · Cited by 41
Long-lived Inflammatory Signaling in Irradiated Bone Marrow Is Genome Dependent
Lorimore, S. A., Mukherjee, D., Robinson, J. I., Chrystal, J. A., & Wright, E. G. (2011) · Cancer Research · doi:10.1158/0008-5472.can-11-1926 · Cited by 42
Sesamol prevents doxorubicin-induced oxidative damage and toxicity on H9c2 cardiomyoblasts
Nayak, P. G., Mudgal, P. P., Bansal, P., Kutty, N. G., & Pai, K. S. R. (2013) · Journal of Pharmacy and Pharmacology · doi:10.1111/jphp.12073 · Cited by 41
“An improved cellular antioxidant profile in turn reduces the stress on the normal cell cycle,([71,72]) thus preventing any disturbance in the genetic expression of several pro-apoptotic and anti-apoptotic proteins, caused by a toxicant.”
BackgroundCrosstalk between Oxidative Stress and Aging in Neurodegeneration Disorders
Abdelhamid, R. F., & Nagano, S. (2023) · Cells · doi:10.3390/cells12050753 · Cited by 44
Wyrobek, A. J., Manohar, C. F., Krishnan, V. V., Nelson, D. O., Furtado, M. R., Bhattacharya, M. S., Marchetti, F., & Coleman, M. A. (2011) · Mutation Research/Genetic Toxicology and Environmental Mutagenesis · doi:10.1016/j.mrgentox.2011.03.002 · Cited by 40
“and slope of the low dose response curves for gene expression and the associated molecular functions, both of which are needed to assess relevance of the LNT model [43].”
BackgroundLiu, B., Bhatt, D., Oltvai, Z. N., Greenberger, J. S., & Bahar, İ. (2014) · Scientific Reports · doi:10.1038/srep06245 · Cited by 43
Protection against radiation-induced oxidative damage by an ethanolic extract ofNigella sativaL.
Rastogi, L., Feroz, S., Pandey, B. N., Jagtap, A., & Mishra, K. P. (2010) · International Journal of Radiation Biology · doi:10.3109/09553002.2010.484480 · Cited by 40
“Free radicals are constantly produced in living systems as a consequence of intrinsic aerobic metabolic processes and after exposure to genotoxic agents like ionising radiation (Halliwell and Gutteridge 1989, Bauer and Bauer 1999, Droge 2002, Spitz et al. 2004).”
BackgroundProtective effect of 5, 7-dihydroxyflavone on brain of rats exposed to acrylamide or γ-radiation
Mansour, S. Z., Moawed, F. S., & Elmarkaby, S. M. (2017) · Journal of Photochemistry and Photobiology B Biology · doi:10.1016/j.jphotobiol.2017.08.034 · Cited by 40
Reactive oxygen species and nitric oxide signaling in bystander cells
Jella, K. K., Moriarty, R. D., McClean, B., Byrne, H. J., & Lyng, F. M. (2018) · PLoS ONE · doi:10.1371/journal.pone.0195371 · Cited by 40
“The cellular stress produced by radiation may persist for a longer time due to its effects on oxidative metabolism [59].”
BackgroundMetabolic regulation of Sirtuins upon fasting and the implication for cancer
Zhu, Y., Yan, Y., Gius, D. R., & Vassilopoulos, A. (2013) · Current Opinion in Oncology · doi:10.1097/01.cco.0000432527.49984.a3 · Cited by 43
Fu, T., Hou, Y., Chu, S., Liu, C., Huang, C., Chen, H., Hsiao, M., Lu, P., Wang, J., & Ger, L. (2011) · Head & Neck · doi:10.1002/hed.21653 · Cited by 39
“Following radiotherapy, increased oxidative stress up-regulates cellular antioxidant defense mechanisms to remove free radicals (and ROS), thus providing maximal protection for biological sites.(32) Kalen and colleagues(36) proposed that MnSOD overexpression enhances G2 accumulation and radioresistance in human carcin…”
BackgroundMapuskar, K. A., Flippo, K. H., Schoenfeld, J. D., Riley, D. P., Strack, S., Hejleh, T. A., Furqan, M., Monga, V., Domann, F. E., Buatti, J. M., et al. (2017) · Cancer Research · doi:10.1158/0008-5472.can-17-0106 · Cited by 42
“Furthermore, normal tissue injury associated with cancer therapy has been hypothesized to involve alterations to mitochondrial oxidative metabolism leading to increased steady-state levels of reactive oxygen species (ROS) including superoxide (O2 ) and hydrogen peroxide (H2O2) (7,8).”
BackgroundInfluentialSoliman, A. F., Saif‐Elnasr, M., & Fattah, S. M. A. (2019) · Life Sciences · doi:10.1016/j.lfs.2019.01.024 · Cited by 39
Apigenin in cancer therapy: Prevention of genomic instability and anticancer mechanisms
Moslehi, M., Rezaei, S., Talebzadeh, P., Ansari, M. J., Jawad, M. A., Jalil, A. T., Rastegar‐Pouyani, N., Jafarzadeh, E., Taeb, S., & Najafi, M. (2022) · Clinical and Experimental Pharmacology and Physiology · doi:10.1111/1440-1681.13725 · Cited by 39
“ionizing radiation causes immune responses that may lead to the disruption of redox metabolism and overproduction of endogenous ROS by cells.(48) Mitochondria is the main source of ROS generation in cells”
BackgroundGao, W., Liang, J., Ma, C., Dong, J., & Yan, Q. (2017) · BioMed Research International · doi:10.1155/2017/4176170 · Cited by 39
Deciphering the complexities of cancer cell immune evasion: Mechanisms and therapeutic implications
Gupta, I., Hussein, O., Sastry, K. S., Bougarn, S., Gopinath, N., Chin-Smith, E. C., Sinha, Y., Korashy, H. M., & Maccalli, C. (2023) · Advances in Cancer Biology - Metastasis · doi:10.1016/j.adcanc.2023.100107 · Cited by 39
Khanbeigi, R. A., Abelha, T. F., Woods, A., Rastoin, O., Harvey, R. D., Jones, M., Forbes, B., Green, M., Collins, H., & Dailey, L. A. (2015) · Biomacromolecules · doi:10.1021/bm501649y · Cited by 38
Fakhri, S., Piri, S., Moradi, S. Z., & Khan, H. Z. (2021) · Current Neuropharmacology · doi:10.2174/1570159x19666210809103346 · Cited by 39
“Several signaling pathways are activated in response to ionizing radiation, such as PKC, MAPK, p53, NF-κB, ataxia telangiectasia mutated (ATM), and DNA-dependent protein kinase (DNAPK) [45].”
In situ observation of mitochondrial biogenesis as the early event of apoptosis
Shao, C., Zhou, X., Miao, Y., Wang, P., Zhang, Q., & Huang, Q. (2021) · iScience · doi:10.1016/j.isci.2021.103038 · Cited by 38
“Ionizing radiation has been used for cancer therapy for they can directly or indirectly cause DNA damage and kill the cancer cells (Spitz et al., 2004).”
BackgroundXiao, W., Sarsour, E. H., Wagner, B. A., Doskey, C. M., Buettner, G. R., Domann, F. E., & Goswami, P. C. (2014) · Archives of Toxicology · doi:10.1007/s00204-014-1407-3 · Cited by 38
“NADH and FADH2 transfer electrons through complex I, II, and III of the mitochondrial electron transport chain (MTEC) leading to the reduction of molecular oxygen at complex IV and generation of energy (ATP) at complex V (Balaban et al. 2005; Spitz et al. 2004).”
InfluentialMechanisms for Radioprotection by Melatonin; Can it be Used as a Radiation Countermeasure?
Amini, P., Mirtavoos‐Mahyari, H., Motevaseli, E., Shabeeb, D., Musa, A. E., Cheki, M., Farhood, B., Yahyapour, R., Shirazi, A., Goushbolagh, N. A., et al. (2018) · Current Molecular Pharmacology · doi:10.2174/1874467211666180802164449 · Cited by 38
What role for DNA damage and repair in the bystander response?
Prise, K. M., Folkard, M., Kuosaite, V., Tartier, L., Zyuzikov, N. A., & Shao, C. (2006) · Mutation research. Fundamental and molecular mechanisms of mutagenesis · doi:10.1016/j.mrfmmm.2005.06.034 · Cited by 38
Monounsaturated fatty acids promote cancer radioresistance by inhibiting ferroptosis through ACSL3
Cao, Y., Li, J., Chen, Y., Wang, Y., Liu, Z., Huang, L., Liu, B., Feng, Y., Yao, S., Zhou, L., et al. (2025) · Cell Death and Disease · doi:10.1038/s41419-025-07516-0 · Cited by 40
“In addition to causing DNA damage, RT also generates reactive oxygen species (ROS), which can induce oxidative damage to cell components including lipid membranes [4, 5].”
Baulch, J. E. (2018) · International Journal of Radiation Biology · doi:10.1080/09553002.2018.1549757 · Cited by 37
“As the hub of energy production, mitochondria constitute a major intracellular source of reactive species, especially under conditions of metabolic stress that perturb oxidative phosphorylation (Spitz et al. 2004).”
BackgroundResultTan, R., He, Y., Zhang, S., Pu, D., & Wu, J. (2019) · Journal of Ovarian Research · doi:10.1186/s13048-019-0541-1 · Cited by 37
Santovito, A., Cervella, P., & Delpero, M. (2014) · Environmental Toxicology and Pharmacology · doi:10.1016/j.etap.2013.12.009 · Cited by 37
“One consequence of the exposure to IR is the formation of free radicals, such as peroxynitrites and hydroxyl radicals (Zhang et al., 2000; Spitz et al., 2004), able to produce some important alterations in the living cells.”
BackgroundRedox Regulation of Nrf2 in Cisplatin-Induced Kidney Injury
Mapuskar, K. A., Pulliam, C. F., Zepeda‐Orozco, D., Griffin, B. R., Furqan, M., Spitz, D. R., & Allen, B. G. (2023) · Antioxidants · doi:10.3390/antiox12091728 · Cited by 37
Taurine provides a time-dependent amelioration of the brain damage induced by γ-irradiation in rats
El-Maraghi, E. F., Abdel-Fattah, K. I., Soliman, S. M., & El-Sayed, W. M. (2018) · Journal of Hazardous Materials · doi:10.1016/j.jhazmat.2018.07.005 · Cited by 36
Regulation of normal cell cycle progression by flavin-containing oxidases
Venkatachalam, P., de Toledo, S. M., Pandey, B. N., Tephly, L. A., Carter, A. B., Little, J. B., Spitz, D. R., & Azzam, E. I. (2007) · Oncogene · doi:10.1038/sj.onc.1210634 · Cited by 36
“Hence, homeostatic cellular functions require tight control of the cellular redox environment (Spitz et al., 2004).”
BackgroundFerroptosis induction via targeting metabolic alterations in triple-negative breast cancer
Wang, Y., Sun, Y., Wang, F., Wang, H., & Hu, J. (2023) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2023.115866 · Cited by 37
Irradiation to the young mouse brain impaired white matter growth more in females than in males
Roughton, K., Boström, M., Kalm, M., & Blomgren, K. (2013) · Cell Death and Disease · doi:10.1038/cddis.2013.423 · Cited by 34
Tan, M., Zhu, Y., Kovacev, J., Zhao, Y., Pan, Z., Spitz, D. R., & Sun, Y. (2010) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2010.05.030 · Cited by 34
“Radiolysis of water caused by ionizing radiation produces ROS which can cause oxidative damage to critical bimolecules leading to persistent increases in steady-state levels of intracellular ROS which are believed to contribute to the biological effects of radiation [35– 38].”
Hesperidin attenuates brain biochemical changes of irradiated rats
Said, U. Z., Saada, H. N., Abdalla, M. S., Elsayed, M. E., & Amin, A. M. (2012) · International Journal of Radiation Biology · doi:10.3109/09553002.2012.694008 · Cited by 34
PDGF-mimicking supramolecular nanofibers for ionizing radiation-induced injury repair
Shang, Y., Liu, H., Peng, R., Ren, C., Luo, X., Ma, C., Gao, Y., Wang, Z., Gao, J., Liu, J., et al. (2020) · Chemical Engineering Journal · doi:10.1016/j.cej.2020.128309 · Cited by 33
Goel, A., Spitz, D. R., & Weiner, G. J. (2011) · Journal of Cellular Biochemistry · doi:10.1002/jcb.23387 · Cited by 33
“) causing cytotoxicity by covalent alterations in DNA, proteins, and lipids [Spitz et al., 2004].”
BackgroundInfluentialEldridge, A., Fan, M., Woloschak, G. E., Grdina, D. J., Chromy, B. A., & Li, J. J. (2012) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2012.08.589 · Cited by 33
“MnSOD helps to eliminate free radicals in the mitochondria by converting superoxide anions to H2O2, which can then be detoxified by the catalase activity of peroxidase [13].”
BackgroundThe potential of ferroptosis combined with radiotherapy in cancer treatment
Lu, Z., Xiao, B., Chen, W., Tang, T., Zhuo, Q., & Chen, X. (2023) · Frontiers in Oncology · doi:10.3389/fonc.2023.1085581 · Cited by 35
“RT can cause oxidative damage to all cell compartments, including the lipid membrane (105, 106).”
BackgroundZhang, S., Song, C., Zhou, J., Ling, X., Meng, X., Liu, P., Cao, J., Zhang, X., Ding, W., & Wu, J. (2012) · Radiation Oncology · doi:10.1186/1748-717x-7-4 · Cited by 32
“Many of these signaling and gene expression pathways are involved in intracellular metabolic redox reactions to buffer the ROS [8].”
BackgroundInfluentialEl-Azime, A. S. A., Hussein, E. M., & Ashry, O. M. (2014) · International Journal of Radiation Biology · doi:10.3109/09553002.2014.926040 · Cited by 32
“Radiation damage is largely caused by the overproduction of reactive oxygen species (ROS) including Superoxide anion O2 -, hydroxyl radical (HO-), hydrogen peroxide (H2O2) that overwhelm the levels of antioxidants resulting in oxidative stress (Spitz et al. 2004) that are known to cause abnormal chemical reactions in…”
BackgroundRadiation Induced Bystander Effect: From in Vitro Studies to Clinical Application
Wideł, M. (2016) · International Journal of Medical Physics Clinical Engineering and Radiation Oncology · doi:10.4236/ijmpcero.2016.51001 · Cited by 31
Circular RNAs in the Regulation of Oxidative Stress
Zhang, Y., Chen, Y., Wan, Y., Zhao, Y., Wen, Q., Tang, X., Shen, J., Wu, X., Li, M., Li, X., et al. (2021) · Frontiers in Pharmacology · doi:10.3389/fphar.2021.697903 · Cited by 32
“These changes are not just restricted to the cells exposed to the ionizing radiations but instead also affect their offspring (Mothersill and Seymour, 2004; Spitz et al., 2004; Prise and O’Sullivan, 2009).”
BackgroundSridharan, V., Tripathi, P., Aykin‐Burns, N., Krager, K. J., Sharma, S., Moros, E. G., Melnyk, S. B., Pavliv, O., Hauer‐Jensen, M., & Boerma, M. (2015) · Radiation Research · doi:10.1667/rr13915.1 · Cited by 32
“This may lead to metabolic oxidative stress that contributes to the biological effects of radiation long after the time of exposure (30).”
Deoxycytidine Kinase Augments ATM-Mediated DNA Repair and Contributes to Radiation Resistance
Bunimovich, Y. L., Nair‐Gill, E., Riedinger, M., McCracken, M. N., Cheng, D., McLaughlin, J., Radu, C. G., & Witte, O. N. (2014) · PLoS ONE · doi:10.1371/journal.pone.0104125 · Cited by 32
“Ionizing radiation leads to oxidative stress through the formation of free radicals [49].”
BackgroundShuryak, I., & Brenner, D. J. (2009) · Journal of Theoretical Biology · doi:10.1016/j.jtbi.2009.08.003 · Cited by 32
“For example, oxidative stress triggered by even quite low doses of radiation can produce an alteration of the cellular redox balance, which lasts for substantial time after exposure and may contribute to bystander effects, genomic instability, modified gene expression, elevated mutagenesis rates, changes in cell survi…”
Saada, H. N., Said, U. Z., Mahdy, E.-S. M. E., Elmezayen, H. E., & Shedid, S. M. (2014) · International Journal of Radiation Biology · doi:10.3109/09553002.2014.934928 · Cited by 32
“If the damage is irreparable, then injury, mutagenesis, carcinogenesis, accelerated senescence and cell death can occur (Spitz et al. 2004).”
BackgroundThe biochemical changes in rats blood serum levels exposed to different gamma radiation doses
Abdel-Halim, K. Y. (2013) · African Journal of Pharmacy and Pharmacology · doi:10.5897/ajpp2013.3434 · Cited by 32
“If this damage is irreparable, then injury, mutagenesis, carcinogenesis, accelerated senescence, and cell death can occur (Spitz et al., 2004).”
BackgroundAykin‐Burns, N., Slane, B. G., Liu, A. T. Y., Owens, K. M., O'Malley, M. S., Smith, B. J., Domann, F. E., & Spitz, D. R. (2010) · Radiation Research · doi:10.1667/rr2220.1 · Cited by 34
Ibrahim, N. K. (2011) · doi:10.5281/zenodo.1329505 · Cited by 32
El‐Nashar, H. A. S., Eldahshan, O. A., Elshawi, O. E., & Singab, A. N. B. (2017) · Drug Development Research · doi:10.1002/ddr.21395 · Cited by 31
“CCl4 alone and in combination with IRR decreased (p 0.001) GSH concentrations as well as GPx, SOD, and CAT activities.”
BackgroundMethodInfluentialNeuroimaging in Pregnant Women
Chansakul, T., & Young, G. S. (2017) · Seminars in Neurology · doi:10.1055/s-0037-1608939 · Cited by 31
Natarajan, M., Gibbons, C. F., Mohan, S., Moore, S. R., & Kadhim, M. (2007) · British Journal of Radiology · doi:10.1259/bjr/15316848 · Cited by 31
“In addition, it has been shown previously that induced levels of TNFa in the culture medium are capable of inducing oxidative stress in target cells [26, 27].”
BackgroundLee, H. C., Her, N.-G., Kang, D., Jung, S. H., Shin, J., Lee, M. Y., Bae, I. H., Kim, Y.-N., Park, H. J., Ko, Y., et al. (2017) · Cell Death and Disease · doi:10.1038/cddis.2017.116 · Cited by 31
“Each cell determines whether the cell will die, repair the damage, or proceed through cellular division despite the damage after a critical period from radiation exposure.(20) On the molecular level, radiation-induced damage initiates a complex signaling cascade in cells, resulting in a variety of responses that inclu…”
BackgroundStudy on the oxidative stress status among cement plant workers
Pournourmohammadi, S., Khazaeli, P., Eslamizad, S., Tajvar, A., Mohammadirad, A., & Abdollahi, M. R. (2008) · Human & Experimental Toxicology · doi:10.1177/0960327108094956 · Cited by 31
Buonanno, M., Gonon, G., Pandey, B. N., & Azzam, E. I. (2022) · International Journal of Radiation Biology · doi:10.1080/09553002.2022.2078006 · Cited by 30
“Several mechanisms have been shown to mediate RIBE with intercellular communications and oxidative metabolism being extensively investigated (reviewed in Azzam et al. 2003b; Spitz et al. 2004; Pouget et al. 2018) (Figure 1 with focus on intercellular communications).”
BackgroundPiao, M. J., Kim, K. C., Chae, S., Keum, Y. S., Kim, H. S., & Hyun, J. W. (2013) · Biomolecules & Therapeutics · doi:10.4062/biomolther.2013.017 · Cited by 30
“ROS-scavenging agents, which include fl avonoids, act as radioprotectors (Spitz et al., 2004; Gudkov et al., 2006).”
BackgroundImplications of the Colonic Deposition of Free Hemoglobin-α Chain
Myers, J. N., Schäffer, M. W., Korolkova, O. Y., Williams, A. D., Gangula, P. R., & M’Koma, A. E. (2014) · Inflammatory Bowel Diseases · doi:10.1097/mib.0000000000000144 · Cited by 30
“The detrimental effects of reactive oxygen molecules have been well studied and established in the inflammation sequence.(83) However, the specific pathways leading to cellular damage are not completely elucidated and remain poorly defined, noncomprehensive, and impractical in clinical medicine and in therapeutic adva…”
BackgroundCurative role of pantothenic acid in brain damage of gamma irradiated rats
Shedid, S. M., Saada, H. N., Na, E., & Hammad, A. (2017) · Indian Journal of Clinical Biochemistry · doi:10.1007/s12291-017-0683-0 · Cited by 30
Ferroptosis: A New Promising Target for Ovarian Cancer Therapy
Zhao, H., Xu, Y., & Shang, H. (2022) · International Journal of Medical Sciences · doi:10.7150/ijms.76480 · Cited by 30
“Radiotherapy can induce oxidative damage and lipid peroxidation in all cellular compartments [75].”
BackgroundThe In Vivo Expression of Radiation-Induced Chromosomal Instability Has an Inflammatory Mechanism
Mukherjee, D., Coates, P. J., Lorimore, S. A., & Wright, E. G. (2011) · Radiation Research · doi:10.1667/rr2793.1 · Cited by 30
“In this study, the anti-inflammatory drug Celebrext reduced the persistent long-term inflammatory microenvironment in the bone marrow, supporting proposals for common inflammatory mechanisms underlying these various indirect in vivo consequences of radiation exposure (3, 6, 51).”
BackgroundLemon, J. A., Rollo, C. D., & Boreham, D. R. (2008) · Mutagenesis · doi:10.1093/mutage/gen036 · Cited by 33
“Following oxidative insults like radiation, cells may express elevated free radical production for weeks or even months (62).”
BackgroundInfluentialVellingiri, B., Sureshkumar, S., Subramaniam, M. D., Balasubramanian, B., Meyyazhagan, A., Karthickkumar, A., Prakash, V., Shafiahammedkhan, M., Sankar, K., Pappuswamy, M., et al. (2013) · Ecotoxicology and Environmental Safety · doi:10.1016/j.ecoenv.2013.09.036 · Cited by 30
“It has been clearly explained that the initial radiation-induced free-radical insult may also cause chromosome breaks and chromatid exchange and chromosomes may remain structurally perturbed for a long (Spitz et al., 2004).”
BackgroundWang, S.-H., Chen, Y., Hsiao, J., Tsai, F.-Y., Jiang, S. S., Lee, A. Y.-L., Tsai, H.-J., & Chen, Y. (2021) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-021-01898-7 · Cited by 30
Engin, A. B., Ergün, M. A., Yurtçu, E., Kan, D., & Şahin, G. (2005) · Mutation Research/Genetic Toxicology and Environmental Mutagenesis · doi:10.1016/j.mrgentox.2005.05.005 · Cited by 29
PIXE analysis of trace elements in relation to chlorophyll concentration in Plantago ovata Forsk
Saha, P., Raychaudhuri, S. S., Chakraborty, A., & Sudarshan, M. (2009) · Applied Radiation and Isotopes · doi:10.1016/j.apradiso.2009.12.003 · Cited by 29
Giardi, M. T., Touloupakis, E., Bertolotto, D., & Mascetti, G. (2013) · International Journal of Molecular Sciences · doi:10.3390/ijms140817168 · Cited by 30
“It can also act indirectly through radiolysis of water, thereby generating reactive chemical species that may damage DNA, proteins and lipids [46].”
BackgroundLin, Y. H., Han, Y., Xu, J., Cao, L., Gao, J., Xie, N., Zhao, X., Jiang, H., & Chi, Z. (2010) · Cellular and Molecular Neurobiology · doi:10.1007/s10571-010-9524-x · Cited by 31
“Oxidative damage in mtDNA might influence the expression of these peptides and subsequently contribute to mitochondrial oxidative phosphorylation (OXPHOS) deficiency, which results in increased ROS production, thus a continuation of a vicious cycle (Wallace 1992; Spitz et al. 2004).”
BackgroundYanase, S., & Ishii, N. (2008) · Journal of Radiation Research · doi:10.1269/jrr.07043 · Cited by 29
Oxidative stress and low dose ionizing radiation.
Puthran, S. S., Sudha, K., Rao, G. M., & Shetty, B. (2009) · PubMed · Cited by 29
Metadata
- 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
- Licence
- 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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
