title: Induction of oxidative stress, DNA damage, and apoptosis in a malignant human skin melanoma cell line after exposure to zinc oxide nanoparticles.
abstract: The widespread use of zinc oxide (ZnO) nanoparticles worldwide exposes humans to their adverse effects, so it is important to understand their biological effects and any associated risks. This study was designed to investigate the cytotoxicity, oxidative stress, and apoptosis caused by ZnO nanoparticles in human skin melanoma (A375) cells. MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide] and lactate dehydrogenase-based cell viability assays showed a significant decrease in cell viability after exposure to ZnO nanoparticles, and phase contrast images revealed that cells treated with these nanoparticles had a lower density and a rounded morphology. ZnO nanoparticles were also found to induce oxidative stress, evidenced by generation of reactive oxygen species and depletion of the antioxidant, glutathione. Induction of apoptosis was confirmed by chromosomal condensation assay and caspase-3 activation. Further, more DNA damage was observed in cells exposed to the highest concentration of ZnO nanoparticles. These results demonstrate that ZnO nanoparticles have genotoxic potential in A375 cells, which may be mediated via oxidative stress. Our short-term exposure study showing induction of a genotoxic and apoptotic response to ZnO nanoparticles needs further investigation to determine whether there may be consequences of long-term exposure to ZnO nanoparticles.
authors.affiliation: Department of Zoology, Faculty of Science, King Saud University, Riyadh, Saudi Arabia.
authors.forename: Saud
authors.initials: S
authors.lastname: Alarifi
authors.forename: Daoud
authors.initials: D
authors.lastname: Ali
authors.forename: Saad
authors.initials: S
authors.lastname: Alkahtani
authors.forename: Ankit
authors.initials: A
authors.lastname: Verma
authors.forename: Maqusood
authors.initials: M
authors.lastname: Ahamed
authors.forename: Mukhtar
authors.initials: M
authors.lastname: Ahmed
authors.forename: Hisham A
authors.initials: HA
authors.lastname: Alhadlaq
mesh_terms: D000704:Analysis of Variance; D017209:Apoptosis / Q000187:drug effects*; D014408:Biomarkers, Tumor / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D002877:Chromosomes, Human / Q000187:drug effects; D004249:DNA Damage; D006801:Humans; D015227:Lipid Peroxidation / Q000187:drug effects; D008545:Melanoma / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D053768:Metal Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D018384:Oxidative Stress / Q000187:drug effects*; D017382:Reactive Oxygen Species / Q000378:metabolism; D012878:Skin Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D015034:Zinc Oxide / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D014408:Biomarkers, Tumor; D017382:Reactive Oxygen Species; D053148:Caspase 3; D015034:Zinc Oxide
keywords: DNA damage; apoptosis; oxidative stress; zinc oxide nanoparticles