Open AccessPhysiological Levels of Reactive Oxygen Species Are Required to Maintain Genomic Stability in Stem Cells
Author(s) -
Li TaoSheng,
Marbán Eduardo
Publication year - 2010
Publication title -
stem cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.159
H-Index - 229
eISSN - 1549-4918
pISSN - 1066-5099
DOI - 10.1002/stem.438
Subject(s) - biology , stem cell , dna damage , reactive oxygen species , genome instability , embryonic stem cell , microbiology and biotechnology , carcinogenesis , dna repair , oxidative stress , genetics , biochemistry , dna , gene
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 “oxidative optimum” for genomic stability has broad implications for stem cell biology and carcinogenesis. S TEM C ELLS 2010;28:1178–1185