The DOI matches its Crossref record; 48 of the 48 references it cites were found in a registry or an index.
Total body irradiation causes residual bone marrow injury by induction of persistent oxidative stress in murine hematopoietic stem cells
Open accessAbstract
Ionizing radiation (IR) and/or chemotherapy causes not only acute tissue damage but also late effects including long-term (or residual) bone marrow (BM) injury. The induction of residual BM injury is primarily attributable to the induction of hematopoietic stem cell (HSC) senescence. However, the molecular mechanisms by which IR and/or chemotherapy induces HSC senescence have not been clearly defined, nor has an effective treatment been developed to ameliorate the injury. Thus, we investigated these mechanisms in this study. The results from this study show that exposure of mice to a sublethal dose of total body irradiation (TBI) induced a persistent increase in reactive oxygen species (ROS) production in HSCs only. The induction of chronic oxidative stress in HSCs was associated with sustained increases in oxidative DNA damage, DNA double-strand breaks (DSBs), inhibition of HSC clonogenic function, and induction of HSC senescence but not apoptosis. Treatment of the irradiated mice with N-acetylcysteine after TBI significantly attenuated IR-induced inhibition of HSC clonogenic function and reduction of HSC long-term engraftment after transplantation. The induction of chronic oxidative stress in HSCs by TBI is probably attributable to the up-regulation of NADPH oxidase 4 (NOX4), because irradiated HSCs expressed an increased level of NOX4, and inhibition of NOX activity with diphenylene iodonium but not apocynin significantly reduced TBI-induced increases in ROS production, oxidative DNA damage, and DNA DSBs in HSCs and dramatically improved HSC clonogenic function. These findings provide the foremost direct evidence demonstrating that TBI selectively induces chronic oxidative stress in HSCs at least in part via up-regulation of NOX4, which leads to the induction of HSC senescence and residual BM injury.
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In the citing paper
“Wang et al. observed that persistent elevation of ROS and oxidative DNA damage are associated with increased senescence and decreased clonogenic capacity of hematopoietic stem cells (HSC) [103].”
From Ultraviolet Radiation‐Induced Skin Aging: The Role of DNA Damage and Oxidative Stress in Epidermal Stem Cell Damage Mediated Skin Aging (2016) · cites this paper as [103]
In the citing paper
“Although the mechanisms by which ROS act on molecular changes in ESCs in the process of skin aging are not well understood, it has been shown that elevated ROS is responsible for premature aging of the stem cells of the skin.”
From Ultraviolet Radiation‐Induced Skin Aging: The Role of DNA Damage and Oxidative Stress in Epidermal Stem Cell Damage Mediated Skin Aging (2016) · cites this paper as [103]
In the citing paper
“Our previous studies suggest that IR induces HSC senescence primarily via induction of oxidative stress,9,23,30”
From Total body irradiation causes long-term mouse BM injury via induction of HSC premature senescence in an Ink4a- and Arf-independent manner (2014) · cites this paper as [23]
In the citing paper
“exposure of mice to TBI induced persistent increases in ROS production in HSC-enriched LSK cells, in part via upregulation of nicotinamide adenine dinucleotide phosphate-oxidase 4.23”
From Total body irradiation causes long-term mouse BM injury via induction of HSC premature senescence in an Ink4a- and Arf-independent manner (2014) · cites this paper as [23]
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Citations
Cites
The NOX Family of ROS-Generating NADPH Oxidases: Physiology and Pathophysiology
Bedard, K., & Krause, K.-H. (2007) · Physiological Reviews · doi:10.1152/physrev.00044.2005 · Cited by 6,989
Evidence for a lack of DNA double-strand break repair in human cells exposed to very low x-ray doses
Rothkamm, K., & Löbrich, M. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0830918100 · Cited by 1,645 · cited 1×
“To test this hypothesis, HPCs and HSCs were isolated from control or irradiated mice by cell sorting and immunostained with antibodies against 8-OH-dG and γH2AX to detect oxidative DNA damage and DNA double-strand breaks (DSBs) [23,24], respectively.”
MethodFoxOs Are Critical Mediators of Hematopoietic Stem Cell Resistance to Physiologic Oxidative Stress
Tothova, Z., Kollipara, R., Huntly, B. J., Lee, B. H., Castrillon, D. H., Cullen, D. E., McDowell, E. P., Lazo-Kallanian, S., Williams, I. R., Sears, C., et al. (2007) · Cell · doi:10.1016/j.cell.2007.01.003 · Cited by 1,562
Ink4a/Arf expression is a biomarker of aging
Krishnamurthy, J., Torrice, C., Ramsey, M. R., Kovalev, G. I., Al-Regaiey, K., Su, L., & Sharpless, N. E. (2004) · Journal of Clinical Investigation · doi:10.1172/jci22475 · Cited by 1,486
Reactive oxygen species act through p38 MAPK to limit the lifespan of hematopoietic stem cells
Ito, K., Hirao, A., Arai, F., Takubo, K., Matsuoka, S., Miyamoto, K., Ohmura, M., Naka, K., Hosokawa, K., Ikeda, Y., et al. (2006) · Nature Medicine · doi:10.1038/nm1388 · Cited by 1,362
Regulation of oxidative stress by ATM is required for self-renewal of haematopoietic stem cells
Ito, K., Hirao, A., Arai, F., Matsuoka, S., Takubo, K., Hamaguchi, I., Nomiyama, K., Hosokawa, K., Sakurada, K., Nakagata, N., et al. (2004) · Nature · doi:10.1038/nature02989 · Cited by 1,175 · cited 2×
“Particularly, it inhibited ATMmutation induced increases in ROS production in HSCs [16,17].”
BackgroundMethodDeficiencies in DNA damage repair limit the function of haematopoietic stem cells with age
Rossi, D. J., Bryder, D., Seita, J., Nussenzweig, A., Hoeijmakers, J., & Weissman, I. L. (2007) · Nature · doi:10.1038/nature05862 · Cited by 1,115
Stems Cells and the Pathways to Aging and Cancer
Rossi, D. J., Jamieson, C. H. M., & Weissman, I. L. (2008) · Cell · doi:10.1016/j.cell.2008.01.036 · Cited by 895
Jang, Y.-Y., & Sharkis, S. J. (2007) · Blood · doi:10.1182/blood-2007-05-087759 · Cited by 894
Foxo3a is essential for maintenance of the hematopoietic stem cell pool
Miyamoto, K., Kazuhito, N., & Atsushi, H. (2009) · Kanazawa University Repository for Academic Resources (DSpace) (Kanazawa University) · Cited by 888
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Modulation of oxidative stress as an anticancer strategy
Gorrini, C., Harris, I. S., & Mak, T. W. (2013) · Nature Reviews Drug Discovery · doi:10.1038/nrd4002 · Cited by 3,579
Jiang, F., Zhang, Y., & Dusting, G. J. (2011) · Pharmacological Reviews · doi:10.1124/pr.110.002980 · Cited by 585
Reactive Oxygen Species in Normal and Tumor Stem Cells
Zhou, D., Shao, L., & Spitz, D. R. (2014) · Advances in cancer research · doi:10.1016/b978-0-12-420117-0.00001-3 · Cited by 412
Self-citationPanich, U., Sittithumcharee, G., Rathviboon, N., & Jirawatnotai, S. (2016) · Stem Cells International · doi:10.1155/2016/7370642 · Cited by 374
Hematopoietic Stem Cell Injury Induced by Ionizing Radiation
Shao, L., Luo, Y., & Zhou, D. (2013) · Antioxidants and Redox Signaling · doi:10.1089/ars.2013.5635 · Cited by 344
Self-citation
Metadata
- Authors
- Wang, Y., Liu, L., Pazhanisamy, S. K., Li, H., Meng, A., & Zhou, D.
- Affiliations
- Medical University of South Carolina (US)
- Corresponding author
- Zhou, Daohong
- Venue
- Free Radical Biology and Medicine
- Publisher
- Elsevier BV
- Published
- 2010-01
- Volume
- 48
- Issue
- 2
- Pages
- 348-356
- ISSN
- 0891-5849 (ISSN-L)
- PMC
- PMC2818724
- OpenAlex
- W2008484243
- Cited by
- 273
- References
- 47
- Citations by year
- 2026: 7 · 2025: 9 · 2024: 14 · 2023: 13 · 2022: 10 · 2021: 12 · 2020: 20 · 2019: 19 · 2018: 27 · 2017: 21 · 2016: 13 · 2015: 25 · 2014: 19 · 2013: 23 · 2012: 22
- FWCI
- 10.27
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Free Radical Biology and Medicine (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Medical University of South Carolina
- National Natural Science Foundation of China
- Hollings Cancer Center, Medical University of South Carolina
- National Cancer Institute (CA102558, R01CA102558, R01CA122023, R01CA078688, R01-CA086688, R01CA086860, P30CA138313)
- National Institute of Allergy and Infectious Diseases (R01AI080421)
- National Center for Research Resources (C06RR014516)
- Topics
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Effects of Radiation Exposure
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Keywords
- total body irradiation, oxidative stress, reactive oxygen species, NOX4, oxidative DNA damage, DNA double-strand breaks, N-acetylcysteine, diphenyleneiodonium, apocynin, long-term engraftment
- MeSH terms
- NADPH Oxidase 4, Acetylcysteine, Animals, Bone Marrow, Cells, Cultured, DNA Damage, Female, Gene Expression Regulation, Hematopoietic Stem Cells, Male, Mice, Inbred C57BL, Onium Compounds, Radiation Injuries, Experimental, Whole-Body Irradiation, Reactive Oxygen Species, Hematopoietic Stem Cell Transplantation, Oxidative Stress, NADPH Oxidases, Transplantation Tolerance, Cell Proliferation, Mice
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