{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T15:04:44Z","timestamp":1790694284441,"version":"4.1.0"},"reference-count":35,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2010,5,4]],"date-time":"2010-05-04T00:00:00Z","timestamp":1272931200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"NIH","award":["R01HL083109"],"award-info":[{"award-number":["R01HL083109"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2010,7,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Stem cell cytogenetic abnormalities constitute a roadblock to regenerative therapies. We investigated the possibility that reactive oxygen species (ROSs) influence genomic stability in cardiac and embryonic stem cells. Karyotypic abnormalities in primary human cardiac stem cells were suppressed by culture in physiological (5%) oxygen, but addition of antioxidants to the medium unexpectedly increased aneuploidy. Intracellular ROS levels were moderately decreased in physiological oxygen, but dramatically decreased by the addition of high-dose antioxidants. Quantification of DNA damage in cardiac stem cells and in human embryonic stem cells revealed a biphasic dose-dependence: antioxidants suppressed DNA damage at low concentrations, but potentiated such damage at higher concentrations. High-dose antioxidants decreased cellular levels of ATM (ataxia-telangiectasia mutated) and other DNA repair enzymes, providing a potential mechanistic basis for the observed effects. These results indicate that physiological levels of intracellular ROS are required to activate the DNA repair pathway for maintaining genomic stability in stem cells. The concept of an \u201coxidative optimum\u201d for genomic stability has broad implications for stem cell biology and carcinogenesis.<\/jats:p>","DOI":"10.1002\/stem.438","type":"journal-article","created":{"date-parts":[[2010,5,4]],"date-time":"2010-05-04T23:29:09Z","timestamp":1273015749000},"page":"1178-1185","source":"Crossref","is-referenced-by-count":134,"title":["Physiological Levels of Reactive Oxygen Species Are Required to Maintain Genomic Stability in Stem Cells"],"prefix":"10.1093","volume":"28","author":[{"given":"Tao-Sheng","family":"Li","sequence":"first","affiliation":[{"name":"The Heart Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eduardo","family":"Marb\u00e1n","sequence":"additional","affiliation":[{"name":"The Heart Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2010,5,4]]},"reference":[{"key":"2022011217454681700_bib1","doi-asserted-by":"crossref","first-page":"1099","DOI":"10.1038\/ng1631","article-title":"Genomic alterations in cultured human embryonic stem cells","volume":"37","author":"Maitra","year":"2005","journal-title":"Nat Genet"},{"key":"2022011217454681700_bib2","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1038\/nbt1285","article-title":"Adaptation to culture of human embryonic stem cells and oncogenesis in vivo","volume":"25","author":"Baker","year":"2007","journal-title":"Nat Biotechnol"},{"key":"2022011217454681700_bib3","doi-asserted-by":"crossref","first-page":"896","DOI":"10.1161\/CIRCULATIONAHA.106.655209","article-title":"Regenerative potential of cardiosphere-derived cells expanded from percutaneous endomyocardial biopsy specimens","volume":"115","author":"Smith","year":"2007","journal-title":"Circulation"},{"key":"2022011217454681700_bib4","doi-asserted-by":"crossref","first-page":"e7195","DOI":"10.1371\/journal.pone.0007195","article-title":"Validation of the cardiosphere method to culture cardiac progenitor cells from myocardial tissue","volume":"4","author":"Davis","year":"2009","journal-title":"Plos One"},{"key":"2022011217454681700_bib5","doi-asserted-by":"crossref","first-page":"3035","DOI":"10.1158\/0008-5472.CAN-04-4194","article-title":"Spontaneous human adult stem cell transformation","volume":"65","author":"Rubio","year":"2005","journal-title":"Cancer Res"},{"key":"2022011217454681700_bib6","doi-asserted-by":"crossref","first-page":"319","DOI":"10.3727\/096368909788534906","article-title":"A transformed cell population derived from cultured mesenchymal stem cells has no functional effect after transplantation into the injured heart","volume":"18","author":"Furlani","year":"2009","journal-title":"Cell Transplant"},{"key":"2022011217454681700_bib7","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1002\/jcp.21690","article-title":"Hypoxia or in situ normoxia: The stem cell paradigm","volume":"219","author":"Ivanovic","year":"2009","journal-title":"J Cell Physiol"},{"key":"2022011217454681700_bib8","doi-asserted-by":"crossref","first-page":"7915","DOI":"10.1073\/pnas.90.17.7915","article-title":"Oxidants, antioxidants, and the degenerative diseases of aging","volume":"90","author":"Ames","year":"1993","journal-title":"Proc Natl Acad Sci USA"},{"key":"2022011217454681700_bib9","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1038\/35056049","article-title":"Chromosomal stability and the DNA double-stranded break connection","volume":"2","author":"van Gent","year":"2001","journal-title":"Nat Rev Genet"},{"key":"2022011217454681700_bib10","volume-title":"An International System for Human Cytogenetic Nomenclature","author":"Shaffer","year":"2009","edition":"1st edition"},{"key":"2022011217454681700_bib11","doi-asserted-by":"crossref","first-page":"1710","DOI":"10.1016\/j.healun.2005.03.019","article-title":"Revision of the 1990 working formulation for the standardization of nomenclature in the diagnosis of heart rejection","volume":"24","author":"Stewart","year":"2005","journal-title":"J Heart Lung Transplant"},{"key":"2022011217454681700_bib12","doi-asserted-by":"crossref","first-page":"1874","DOI":"10.1634\/stemcells.2008-0156","article-title":"Derivation of euploid human embryonic stem cells from aneuploid embryos","volume":"26","author":"Lavon","year":"2008","journal-title":"Stem Cells"},{"key":"2022011217454681700_bib13","article-title":"Chromosome abnormalities and cancer cytogenetics","volume":"1","author":"Lobo","year":"2008","journal-title":"Nature Educ"},{"key":"2022011217454681700_bib14","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1089\/clo.2006.8.108","article-title":"Establishment of new mouse embryonic stem cell lines is improved by physiological glucose and oxygen","volume":"8","author":"Wang","year":"2006","journal-title":"Cloning Stem Cells"},{"key":"2022011217454681700_bib15","doi-asserted-by":"crossref","first-page":"745","DOI":"10.1111\/j.1474-9726.2007.00336.x","article-title":"Reduced oxygen tension attenuates differentiation capacity of human mesenchymal stem cells and prolongs their lifespan","volume":"6","author":"Fehrer","year":"2007","journal-title":"Aging Cell"},{"key":"2022011217454681700_bib16","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1038\/sj.jcbfm.9600517","article-title":"The nitrone disodium 2,4-sulphophenyl-N-tert-butylnitrone is without cytoprotective effect on sodium nitroprusside-induced cell death in N1E-115 neuroblastoma cells in vitro","volume":"28","author":"Hainsworth","year":"2008","journal-title":"J Cereb Blood Flow Metab"},{"key":"2022011217454681700_bib17","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1016\/j.cell.2007.06.044","article-title":"Human alpha B-crystallin mutation causes oxido-reductive stress and protein aggregation cardiomyopathy in mice","volume":"130","author":"Rajasekaran","year":"2007","journal-title":"Cell"},{"key":"2022011217454681700_bib18","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1038\/nature05862","article-title":"Deficiencies in DNA damage repair limit the function of haematopoietic stem cells with age","volume":"447","author":"Rossi","year":"2007","journal-title":"Nature"},{"key":"2022011217454681700_bib19","doi-asserted-by":"crossref","first-page":"4582","DOI":"10.1074\/jbc.M808410200","article-title":"ATM-mediated transcriptional elevation of prion in response to copper-induced oxidative stress","volume":"284","author":"Qin","year":"2009","journal-title":"J Biol Chem"},{"key":"2022011217454681700_bib20","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1038\/nature03442","article-title":"Conserved modes of recruitment of ATM, ATR and DNA-PKcs to sites of DNA damage","volume":"434","author":"Falck","year":"2005","journal-title":"Nature"},{"key":"2022011217454681700_bib21","doi-asserted-by":"crossref","first-page":"466","DOI":"10.1038\/nature04866","article-title":"ATM stabilizes DNA double-strand-break complexes during V(D)J recombination","volume":"442","author":"Bredemeyer","year":"2006","journal-title":"Nature"},{"key":"2022011217454681700_bib22","doi-asserted-by":"crossref","first-page":"969","DOI":"10.1038\/35082110","article-title":"ATR\/ATM-mediated phosphorylation of human Rad17 is required for genotoxic stress responses","volume":"411","author":"Bao","year":"2001","journal-title":"Nature"},{"key":"2022011217454681700_bib23","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1016\/j.jnutbio.2006.10.007","article-title":"A review of the interaction among dietary antioxidants and reactive oxygen species","volume":"18","author":"Seifried","year":"2007","journal-title":"J Nutr Biochem"},{"key":"2022011217454681700_bib24","doi-asserted-by":"crossref","first-page":"e7630","DOI":"10.1371\/journal.pone.0007630","article-title":"Chromosome 7 and 19 trisomy in cultured human neural progenitor cells","volume":"4","author":"Sareen","year":"2009","journal-title":"Plos One"},{"key":"2022011217454681700_bib25","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1002\/gcc.20287","article-title":"Post-transplant lymphoproliferative disorder subtypes correlate with different recurring chromosomal abnormalities","volume":"45","author":"Djokic","year":"2006","journal-title":"Genes Chromosomes Cancer"},{"key":"2022011217454681700_bib26","doi-asserted-by":"crossref","first-page":"2123","DOI":"10.1001\/jama.2008.600","article-title":"Vitamins E and C in the prevention of cardiovascular disease in men: The Physicians' Health Study II randomized controlled trial","volume":"300","author":"Sesso","year":"2008","journal-title":"JAMA"},{"key":"2022011217454681700_bib27","doi-asserted-by":"crossref","first-page":"842","DOI":"10.1001\/jama.297.8.842","article-title":"Mortality in randomized trials of antioxidant supplements for primary and secondary prevention: Systematic review and meta-analysis","volume":"297","author":"Bjelakovic","year":"2007","journal-title":"Jama"},{"key":"2022011217454681700_bib28","doi-asserted-by":"crossref","first-page":"37","DOI":"10.7326\/0003-4819-142-1-200501040-00110","article-title":"Meta-analysis: High-dosage vitamin E supplementation may increase all-cause mortality","volume":"142","author":"Miller","year":"2005","journal-title":"Ann Intern Med"},{"key":"2022011217454681700_bib29","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1038\/nature01485","article-title":"Reactive oxygen species produced by NADPH oxidase regulate plant cell growth","volume":"422","author":"Foreman","year":"2003","journal-title":"Nature"},{"key":"2022011217454681700_bib30","doi-asserted-by":"crossref","first-page":"996","DOI":"10.1038\/nature08119","article-title":"A tissue-scale gradient of hydrogen peroxide mediates rapid wound detection in zebrafish","volume":"459","author":"Niethammer","year":"2009","journal-title":"Nature"},{"key":"2022011217454681700_bib31","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1038\/nature08313","article-title":"Reactive oxygen species prime Drosophila haematopoietic progenitors for differentiation","volume":"461","author":"Owusu-Ansah","year":"2009","journal-title":"Nature"},{"key":"2022011217454681700_bib32","doi-asserted-by":"crossref","first-page":"1563","DOI":"10.1002\/cncr.24130","article-title":"Reduced tumorigenesis in p53 knockout mice exposed in utero to low-dose vitamin E","volume":"115","author":"Chen","year":"2009","journal-title":"Cancer"},{"key":"2022011217454681700_bib33","doi-asserted-by":"crossref","first-page":"1358","DOI":"10.1093\/carcin\/bgi325","article-title":"Enhanced tumorigenesis in p53 knockout mice exposed in utero to high-dose vitamin E","volume":"27","author":"Chen","year":"2006","journal-title":"Carcinogenesis"},{"key":"2022011217454681700_bib34","doi-asserted-by":"crossref","first-page":"3704","DOI":"10.1073\/pnas.93.8.3704","article-title":"Vitamin C pharmacokinetics in healthy volunteers: Evidence for a recommended dietary allowance","volume":"93","author":"Levine","year":"1996","journal-title":"Proc Natl Acad Sci USA"},{"key":"2022011217454681700_bib35","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1373\/clinchem.2006.078865","article-title":"High-dose alpha-tocopherol therapy does not affect HDL subfractions in patients with coronary artery disease on statin therapy","volume":"53","author":"Singh","year":"2007","journal-title":"Clin Chem"}],"container-title":["Stem Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fstem.438","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/stem.438","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/stem.438","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/academic.oup.com\/stmcls\/article-pdf\/28\/7\/1178\/41951101\/stmcls_28_7_1178.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/stmcls\/article-pdf\/28\/7\/1178\/41951101\/stmcls_28_7_1178.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,1,18]],"date-time":"2022-01-18T22:05:12Z","timestamp":1642543512000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/stmcls\/article\/28\/7\/1178-1185\/6400909"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2010,5,4]]},"references-count":35,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2010,5,4]]},"published-print":{"date-parts":[[2010,7,1]]}},"URL":"https:\/\/doi.org\/10.1002\/stem.438","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.3184962.2871062","asserted-by":"object"}]},"ISSN":["1066-5099","1549-4918"],"issn-type":[{"value":"1066-5099","type":"print"},{"value":"1549-4918","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2010,7,1]]},"published":{"date-parts":[[2010,5,4]]}}}