Abstract

BackgroundInhaled nanoparticles have been reported in some instances to translocate from the nostril to the olfactory bulb in exposed rats. In close proximity to the olfactory bulb is the olfactory mucosa, within which resides a niche of multipotent cells. Cells isolated from this area may provide a relevant in vitro system to investigate potential effects of workplace exposure to inhaled zinc oxide nanoparticles.MethodsFour types of commercially-available zinc oxide (ZnO) nanoparticles, two coated and two uncoated, were examined for their effects on primary human cells cultured from the olfactory mucosa. Human olfactory neurosphere-derived (hONS) cells from healthy adult donors were analyzed for modulation of cytokine levels, activation of intracellular signalling pathways, changes in gene-expression patterns across the whole genome, and compromised cellular function over a 24 h period following exposure to the nanoparticles suspended in cell culture medium.ResultsZnO nanoparticle toxicity in hONS cells was mediated through a battery of mechanisms largely related to cell stress, inflammatory response and apoptosis, but not activation of mechanisms that repair damaged DNA. Surface coatings on the ZnO nanoparticles mitigated these cellular responses to varying degrees.ConclusionsThe results indicate that care should be taken in the workplace to minimize generation of, and exposure to, aerosols of uncoated ZnO nanoparticles, given the adverse responses reported here using multipotent cells derived from the olfactory mucosa.

Highlights

  • Inhaled nanoparticles have been reported in some instances to translocate from the nostril to the olfactory bulb in exposed rats

  • In conclusion, we have reported a comprehensive overview of the response of primary human multi-potent cells to uncoated and coated Zinc oxide (ZnO) nanoparticles in an important in vitro model with respect to nasalinhalation exposure

  • We find that surface coatings on ZnO nanoparticles may delay or substantially mitigate the onset of cellular responses depending on the coating composition and other coating characteristics

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Summary

Introduction

Inhaled nanoparticles have been reported in some instances to translocate from the nostril to the olfactory bulb in exposed rats. In close proximity to the olfactory bulb is the olfactory mucosa, within which resides a niche of multipotent cells. Cells isolated from this area may provide a relevant in vitro system to investigate potential effects of workplace exposure to inhaled zinc oxide nanoparticles. Zinc oxide (ZnO) nanoparticles have remarkable ultraviolet (UV) absorbing, optical and optoelectronic properties that make them valuable for a variety of commercial applications [1], including use in sunscreen products where their transparency on the skin and the protection they provide against broad-spectrum UV radiation [2,3] is of consumer benefit. Surface coatings are added to ZnO nanoparticles for ease of handling and to modulate their properties. Surface coating may mitigate two postulated mechanisms of ZnO nanoparticle-mediated cytotoxicity

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