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Surface coatings of ZnO nanoparticles mitigate differentially a host of transcriptional, protein and signalling responses in primary human olfactory cells.

Osmond-McLeod MJ, Osmond RI, Oytam Y, McCall MJ, Feltis B, Mackay-Sim A, Wood SA, Cook AL - Part Fibre Toxicol (2013)

Bottom Line: Four 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.ZnO 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.

View Article: PubMed Central - HTML - PubMed

Affiliation: CSIRO Advanced Materials TCP (Nanosafety), and CSIRO Animal, Food and Health Sciences, PO Box 52, North Ryde, NSW 1670, Australia. megan.osmond@csiro.au.

ABSTRACT

Background: 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.

Methods: Four 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.

Results: ZnO 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.

Conclusions: The 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.

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Related in: MedlinePlus

VENN diagrame showing numbers of unique or shared transcripts within and between different ZnO treatments at 2 h and 6 h. Numbers indicate differentially-expressed transcripts, graphed according to whether they occurred uniquely within one treatment (unshared VENN), or whether they were differentially activated by two or more of the treatments (intersecting VENN). Blank intersections indicate that no genes were unique to that intersection or treatment.
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Figure 6: VENN diagrame showing numbers of unique or shared transcripts within and between different ZnO treatments at 2 h and 6 h. Numbers indicate differentially-expressed transcripts, graphed according to whether they occurred uniquely within one treatment (unshared VENN), or whether they were differentially activated by two or more of the treatments (intersecting VENN). Blank intersections indicate that no genes were unique to that intersection or treatment.

Mentions: To gain a greater insight into the degree of transcriptional variations between treatments, the numbers of unique or shared transcripts across all treatments were counted and plotted in four-way VENN diagrams (Figure 6). At 2 h, the largest number of overlapping transcripts was shared between the uncoated particles (Z-COTE and Nanosun) and the coated HP1 (56 shared transcripts). Thirty transcripts were uniquely shared by Nanosun and Z-COTE, and 17 were shared by all treatments. However, the transcripts that had been uniquely activated by the cytotoxic treatments (Z-COTE, Nanosun, HP1) at 2 h, were also activated by MAX at 6 h, and thus were not ultimately unique to a particular ZnO product. In addition, when these reduced gene lists at 2 h were scrutinised, we found that they comprised transcripts already flagged in Canonical Pathways previously identified using the complete datasets, and no new pathways specific to these intersecting genes were highlighted. The total number of differentially-expressed genes was overall much greater at 6 h than 2 h and, as might be expected with such a large dataset, more genes populated each intersect of the VENN diagram. Nevertheless, by far the greatest number of genes that were differentially expressed was largely shared by all treatments (2380 transcripts). Furthermore, transcripts that were unique to individual treatments or specific intercepts once again, and for the same reasons as discussed above, did not convincingly translate to unique pathways being activated by these treatments when assessed by IPA, but simply appeared to contribute to a stronger perturbation of pathways that had already been identified.


Surface coatings of ZnO nanoparticles mitigate differentially a host of transcriptional, protein and signalling responses in primary human olfactory cells.

Osmond-McLeod MJ, Osmond RI, Oytam Y, McCall MJ, Feltis B, Mackay-Sim A, Wood SA, Cook AL - Part Fibre Toxicol (2013)

VENN diagrame showing numbers of unique or shared transcripts within and between different ZnO treatments at 2 h and 6 h. Numbers indicate differentially-expressed transcripts, graphed according to whether they occurred uniquely within one treatment (unshared VENN), or whether they were differentially activated by two or more of the treatments (intersecting VENN). Blank intersections indicate that no genes were unique to that intersection or treatment.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4016547&req=5

Figure 6: VENN diagrame showing numbers of unique or shared transcripts within and between different ZnO treatments at 2 h and 6 h. Numbers indicate differentially-expressed transcripts, graphed according to whether they occurred uniquely within one treatment (unshared VENN), or whether they were differentially activated by two or more of the treatments (intersecting VENN). Blank intersections indicate that no genes were unique to that intersection or treatment.
Mentions: To gain a greater insight into the degree of transcriptional variations between treatments, the numbers of unique or shared transcripts across all treatments were counted and plotted in four-way VENN diagrams (Figure 6). At 2 h, the largest number of overlapping transcripts was shared between the uncoated particles (Z-COTE and Nanosun) and the coated HP1 (56 shared transcripts). Thirty transcripts were uniquely shared by Nanosun and Z-COTE, and 17 were shared by all treatments. However, the transcripts that had been uniquely activated by the cytotoxic treatments (Z-COTE, Nanosun, HP1) at 2 h, were also activated by MAX at 6 h, and thus were not ultimately unique to a particular ZnO product. In addition, when these reduced gene lists at 2 h were scrutinised, we found that they comprised transcripts already flagged in Canonical Pathways previously identified using the complete datasets, and no new pathways specific to these intersecting genes were highlighted. The total number of differentially-expressed genes was overall much greater at 6 h than 2 h and, as might be expected with such a large dataset, more genes populated each intersect of the VENN diagram. Nevertheless, by far the greatest number of genes that were differentially expressed was largely shared by all treatments (2380 transcripts). Furthermore, transcripts that were unique to individual treatments or specific intercepts once again, and for the same reasons as discussed above, did not convincingly translate to unique pathways being activated by these treatments when assessed by IPA, but simply appeared to contribute to a stronger perturbation of pathways that had already been identified.

Bottom Line: Four 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.ZnO 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.

View Article: PubMed Central - HTML - PubMed

Affiliation: CSIRO Advanced Materials TCP (Nanosafety), and CSIRO Animal, Food and Health Sciences, PO Box 52, North Ryde, NSW 1670, Australia. megan.osmond@csiro.au.

ABSTRACT

Background: 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.

Methods: Four 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.

Results: ZnO 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.

Conclusions: The 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.

Show MeSH
Related in: MedlinePlus