Transcriptome Profiling and Toxicity Following Long-Term, Low Dose Exposure of Human Lung Cells to Ni and NiO Nanoparticles—Comparison with NiCl<sub>2</sub>
Production of nickel (Ni) and nickel oxide (NiO) nanoparticles (NPs) leads to a risk of exposure and subsequent health effects. Understanding the toxicological effects and underlying mechanisms using relevant in vitro methods is, therefore, needed. The aim of this study is to explore changes in gene...
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MDPI AG
2020-03-01
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| Series: | Nanomaterials |
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| Online Access: | https://www.mdpi.com/2079-4991/10/4/649 |
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| author | Anda R. Gliga Sebastiano Di Bucchianico Emma Åkerlund Hanna L. Karlsson |
| author_facet | Anda R. Gliga Sebastiano Di Bucchianico Emma Åkerlund Hanna L. Karlsson |
| author_sort | Anda R. Gliga |
| collection | DOAJ |
| description | Production of nickel (Ni) and nickel oxide (NiO) nanoparticles (NPs) leads to a risk of exposure and subsequent health effects. Understanding the toxicological effects and underlying mechanisms using relevant in vitro methods is, therefore, needed. The aim of this study is to explore changes in gene expression using RNA sequencing following long term (six weeks) low dose (0.5 µg Ni/mL) exposure of human lung cells (BEAS-2B) to Ni and NiO NPs as well as soluble NiCl<sub>2</sub>. Genotoxicity and cell transformation as well as cellular dose of Ni are also analyzed. Exposure to NiCl<sub>2</sub> resulted in the largest number of differentially expressed genes (197), despite limited uptake, suggesting a major role of extracellular receptors and downstream signaling. Gene expression changes for all Ni exposures included genes coding for calcium-binding proteins (<i>S100A14</i> and <i>S100A2</i>) as well as <i>TIMP3</i>, <i>CCND2</i>, <i>EPCAM</i>, <i>IL4R</i> and <i>DDIT4</i>. Several top enriched pathways for NiCl<sub>2</sub> were defined by upregulation of, e.g., interleukin-1A and -1B, as well as Vascular Endothelial Growth Factor A (<i>VEGFA</i>). All Ni exposures caused DNA strand breaks (comet assay), whereas no induction of micronuclei was observed. Taken together, this study provides an insight into Ni-induced toxicity and mechanisms occurring at lower and more realistic exposure levels. |
| first_indexed | 2024-03-10T20:46:34Z |
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| id | doaj.art-194cdf2b5e4443939922e31e6e21705c |
| institution | Directory Open Access Journal |
| issn | 2079-4991 |
| language | English |
| last_indexed | 2024-03-10T20:46:34Z |
| publishDate | 2020-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Nanomaterials |
| spelling | doaj.art-194cdf2b5e4443939922e31e6e21705c2023-11-19T20:15:59ZengMDPI AGNanomaterials2079-49912020-03-0110464910.3390/nano10040649Transcriptome Profiling and Toxicity Following Long-Term, Low Dose Exposure of Human Lung Cells to Ni and NiO Nanoparticles—Comparison with NiCl<sub>2</sub>Anda R. Gliga0Sebastiano Di Bucchianico1Emma Åkerlund2Hanna L. Karlsson3Institute of Environmental Medicine, Karolinska Institutet, 171 77 Stockholm, SwedenInstitute of Environmental Medicine, Karolinska Institutet, 171 77 Stockholm, SwedenInstitute of Environmental Medicine, Karolinska Institutet, 171 77 Stockholm, SwedenInstitute of Environmental Medicine, Karolinska Institutet, 171 77 Stockholm, SwedenProduction of nickel (Ni) and nickel oxide (NiO) nanoparticles (NPs) leads to a risk of exposure and subsequent health effects. Understanding the toxicological effects and underlying mechanisms using relevant in vitro methods is, therefore, needed. The aim of this study is to explore changes in gene expression using RNA sequencing following long term (six weeks) low dose (0.5 µg Ni/mL) exposure of human lung cells (BEAS-2B) to Ni and NiO NPs as well as soluble NiCl<sub>2</sub>. Genotoxicity and cell transformation as well as cellular dose of Ni are also analyzed. Exposure to NiCl<sub>2</sub> resulted in the largest number of differentially expressed genes (197), despite limited uptake, suggesting a major role of extracellular receptors and downstream signaling. Gene expression changes for all Ni exposures included genes coding for calcium-binding proteins (<i>S100A14</i> and <i>S100A2</i>) as well as <i>TIMP3</i>, <i>CCND2</i>, <i>EPCAM</i>, <i>IL4R</i> and <i>DDIT4</i>. Several top enriched pathways for NiCl<sub>2</sub> were defined by upregulation of, e.g., interleukin-1A and -1B, as well as Vascular Endothelial Growth Factor A (<i>VEGFA</i>). All Ni exposures caused DNA strand breaks (comet assay), whereas no induction of micronuclei was observed. Taken together, this study provides an insight into Ni-induced toxicity and mechanisms occurring at lower and more realistic exposure levels.https://www.mdpi.com/2079-4991/10/4/649nickel nanoparticlesgenotoxicitylong-term exposureRNA sequencing |
| spellingShingle | Anda R. Gliga Sebastiano Di Bucchianico Emma Åkerlund Hanna L. Karlsson Transcriptome Profiling and Toxicity Following Long-Term, Low Dose Exposure of Human Lung Cells to Ni and NiO Nanoparticles—Comparison with NiCl<sub>2</sub> Nanomaterials nickel nanoparticles genotoxicity long-term exposure RNA sequencing |
| title | Transcriptome Profiling and Toxicity Following Long-Term, Low Dose Exposure of Human Lung Cells to Ni and NiO Nanoparticles—Comparison with NiCl<sub>2</sub> |
| title_full | Transcriptome Profiling and Toxicity Following Long-Term, Low Dose Exposure of Human Lung Cells to Ni and NiO Nanoparticles—Comparison with NiCl<sub>2</sub> |
| title_fullStr | Transcriptome Profiling and Toxicity Following Long-Term, Low Dose Exposure of Human Lung Cells to Ni and NiO Nanoparticles—Comparison with NiCl<sub>2</sub> |
| title_full_unstemmed | Transcriptome Profiling and Toxicity Following Long-Term, Low Dose Exposure of Human Lung Cells to Ni and NiO Nanoparticles—Comparison with NiCl<sub>2</sub> |
| title_short | Transcriptome Profiling and Toxicity Following Long-Term, Low Dose Exposure of Human Lung Cells to Ni and NiO Nanoparticles—Comparison with NiCl<sub>2</sub> |
| title_sort | transcriptome profiling and toxicity following long term low dose exposure of human lung cells to ni and nio nanoparticles comparison with nicl sub 2 sub |
| topic | nickel nanoparticles genotoxicity long-term exposure RNA sequencing |
| url | https://www.mdpi.com/2079-4991/10/4/649 |
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