title: Cytotoxicity and genotoxicity caused by yttrium oxide nanoparticles in HEK293 cells.
abstract: BACKGROUND
  The increased use of engineered nanoparticles (NPs) has caused new concerns about the potential exposure to biological systems and the potential risk that these materials may pose on human health. Here, we examined the effects of exposure to different concentrations (0-50 μg/mL) and incubation times (10 hours, 24 hours, or 48 hours) of yttrium oxide (Y2O3) NPs on human embryonic kidney (HEK293) cells. Changes in cellular morphology, cell viability, cell membrane integrity, reactive oxygen species levels, mitochondrial membrane potential, cell death (apoptosis and necrosis), and the DNA damage after NP exposure were compared to the effects seen following incubation with paraquat, a known toxicant.
  
  
  RESULTS
  The 24-hour inhibitory concentration 50 (IC50) of Y2O3 NPs (41 ± 5 nm in size) in the HEK293 cells was found to be 108 μg/mL. Incubation with Y2O3 NPs (12.25-50 μg/mL) increased the ratio of Bax/Bcl-2, caspase-3 expression and promoted apoptotic- and necrotic-mediated cell death in both a concentration and a time-dependent manner. Decreases in cell survivability were associated with elevations in cellular reactive oxygen species levels, increased mitochondrial membrane permeability, and evidence of DNA damage, which were consistent with the possibility that mitochondria impairment may play an important role in the cytotoxic response.
  
  
  CONCLUSIONS
  These data demonstrate that the Y2O3 NP exposure is associated with increased cellular apoptosis and necrosis in cultured HEK293 cells.
authors.affiliation: Center for Diagnostic Nanosystems, Marshall University, Huntington, WV, USA.
authors.forename: Vellaisamy
authors.initials: V
authors.lastname: Selvaraj
authors.affiliation: Center for Diagnostic Nanosystems, Marshall University, Huntington, WV, USA.
authors.forename: Sravanthi
authors.initials: S
authors.lastname: Bodapati
authors.affiliation: Department of Integrated Science and Technology, Marshall University, Huntington, WV, USA.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Murray
authors.affiliation: Center for Diagnostic Nanosystems, Marshall University, Huntington, WV, USA.
authors.forename: Kevin M
authors.initials: KM
authors.lastname: Rice
authors.affiliation: Center for Diagnostic Nanosystems, Marshall University, Huntington, WV, USA ; Department of Pharmaceutical Sciences and Research, School of Pharmacy, Marshall University, Huntington, WV, USA.
authors.forename: Nicole
authors.initials: N
authors.lastname: Winston
authors.affiliation: Department of Mechanical Engineering and Engineering Mechanics, Michigan Technological University, Houghton, MI, USA.
authors.forename: Tolou
authors.initials: T
authors.lastname: Shokuhfar
authors.affiliation: Department of Mechanical Engineering and Engineering Mechanics, Michigan Technological University, Houghton, MI, USA.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Center for Diagnostic Nanosystems, Marshall University, Huntington, WV, USA ; Department of Pharmaceutical Sciences and Research, School of Pharmacy, Marshall University, Huntington, WV, USA ; Department of Pharmacology, Physiology and Toxicology, School of Medicine, Marshall University, Huntington, WV, USA.
authors.forename: Eric
authors.initials: E
authors.lastname: Blough
mesh_terms: D016923:Cell Death / Q000187:drug effects*; D043171:Chromosomal Instability / Q000187:drug effects; D004249:DNA Damage; D057809:HEK293 Cells; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D053768:Metal Nanoparticles / Q000008:administration & dosage / Q000633:toxicity* / Q000648:ultrastructure; D009153:Mutagens / Q000008:administration & dosage / Q000633:toxicity*; D050997:Nanomedicine; D010269:Paraquat / Q000633:toxicity; D017382:Reactive Oxygen Species / Q000378:metabolism; D015019:Yttrium / Q000008:administration & dosage / Q000633:toxicity*
chemical_list: D009153:Mutagens; D017382:Reactive Oxygen Species; D015019:Yttrium; D010269:Paraquat; C091417:yttria
keywords: DNA damage; ROS production; apoptosis; cytotoxicity; mitochondria damage; necrosis; yttrium oxide nanoparticles