title: Zinc oxide nanoparticle induced genotoxicity in primary human epidermal keratinocytes.
abstract: Zinc oxide (ZnO) nanoparticles are widely used in cosmetics and sunscreens. Human epidermal keratinocytes may serve as the first portal of entry for these nanoparticles either directly through topically applied cosmetics or indirectly through any breaches in the skin integrity. Therefore, the objective of the present study was to assess the biological interactions of ZnO nanoparticles in primary human epidermal keratinocytes (HEK) as they are the most abundant cell type in the human epidermis. Cellular uptake of nanoparticles was investigated by scanning electron microscopy using back scattered electrons imaging as well as transmission electron microscopy. The electron microscopy revealed the internalization of ZnO nanoparticles in primary HEK after 6 h exposure at 14 microg/ml concentration. ZnO nanoparticles exhibited a time (6-24 h) as well as concentration (8-20 microg/ml) dependent inhibition of mitochondrial activity as evident by the MTT assay. A significant (p < 0.05) induction in DNA damage was observed in cells exposed to ZnO nanoparticles for 6 h at 8 and 14 microg/ml concentrations compared to control as evident in the Comet assay. This is the first study providing information on biological interactions of ZnO nanoparticles with primary human epidermal keratinocytes. Our findings demonstrate that ZnO nanoparticles are internalized by the human epidermal keratinocytes and elicit a cytotoxic and genotoxic response. Therefore, caution should be taken while using consumer products containing nanoparticles as any perturbation in the skin barrier could expose the underlying cells to nanoparticles.
authors.affiliation: Nanomaterial Toxicology Group, Indian Institute of Toxicology Research, Council of Scientific and Industrial Research (CSIR), Mahatma Gandhi Marg, P.O. Box 80, Lucknow 226001, Uttar Pradesh, India.
authors.forename: Vyom
authors.initials: V
authors.lastname: Sharma
authors.forename: Suman K
authors.initials: SK
authors.lastname: Singh
authors.forename: Diana
authors.initials: D
authors.lastname: Anderson
authors.forename: Desmond J
authors.initials: DJ
authors.lastname: Tobin
authors.forename: Alok
authors.initials: A
authors.lastname: Dhawan
mesh_terms: D002478:Cells, Cultured; D000078404:Epidermal Cells; D004817:Epidermis / Q000187:drug effects* / Q000648:ultrastructure; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects* / Q000648:ultrastructure; D053768:Metal Nanoparticles; D008855:Microscopy, Electron, Scanning; D046529:Microscopy, Electron, Transmission; D009153:Mutagens / Q000633:toxicity*; D015034:Zinc Oxide / Q000633:toxicity*
chemical_list: D009153:Mutagens; D015034:Zinc Oxide