title: Differential resistance of human embryonic stem cells and somatic cell types to hydrogen peroxide-induced genotoxicity may be dependent on innate basal intracellular ROS levels.
abstract: Previously, we demonstrated that undifferentiated human embryonic stem cells (hESC) displayed higher resistance to oxidative and genotoxic stress compared to somatic cells, but did not further probe the underlying mechanisms. Using H₂O₂-induced genotoxicity as a model, this study investigated whether higher resistance of hESC to oxidative and genotoxic stress could be due to lower innate basal intracellular levels of reactive oxygen species (ROS), as compared to their differentiated fibroblastic progenies (H1F) and two other somatic cell types - human embryonic palatal mesenchymal (HEPM) cells and peripheral blood lymphocytes (PBL). Comet assay demonstrated that undifferentiated hESC consistently sustained lower levels of DNA damage upon acute exposure to H₂O₂ for 30 min, compared to somatic cells. DCFDA and HE staining with flow cytometry showed that undifferentiated hESC had lower innate basal intracellular levels of reactive oxygen species compared to somatic cells, which could lead to their higher resistance to genotoxic stress upon acute exposure to H₂O₂.
authors.affiliation: Stem Cell Laboratory, Faculty of Dentistry, National University of Singapore, Singapore; Department of Oral & Maxillofacial Surgery, National Dental Centre, SingHealth, Singapore.
authors.forename: Kumar Jayaseelan
authors.initials: KJ
authors.lastname: Vinoth
authors.forename: Jayapal
authors.initials: J
authors.lastname: Manikandan
authors.forename: Swaminathan
authors.initials: S
authors.lastname: Sethu
authors.forename: Lakshmidevi
authors.initials: L
authors.lastname: Balakrishnan
authors.forename: Alexis
authors.initials: A
authors.lastname: Heng
authors.forename: Kai
authors.initials: K
authors.lastname: Lu
authors.forename: Anuradha
authors.initials: A
authors.lastname: Poonepalli
authors.forename: Manoor Prakash
authors.initials: MP
authors.lastname: Hande
authors.forename: Tong
authors.initials: T
authors.lastname: Cao
mesh_terms: D002460:Cell Line; D004249:DNA Damage; D053595:Embryonic Stem Cells / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D006861:Hydrogen Peroxide / Q000633:toxicity*; D059630:Mesenchymal Stem Cells / Q000187:drug effects / Q000378:metabolism*; D009153:Mutagens / Q000633:toxicity*; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism*
chemical_list: D009153:Mutagens; D017382:Reactive Oxygen Species; D006861:Hydrogen Peroxide