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Open AccessArticle

Gene Expression and Epigenetic Changes in Mice Following Inhalation of Copper(II) Oxide Nanoparticles

1
Department of Nanotoxicology and Molecular Epidemiology, Institute of Experimental Medicine of the Czech Academy of Sciences, 14220 Prague, Czech Republic
2
Department of Genetic Toxicology and Epigenetics, Institute of Experimental Medicine of the Czech Academy of Sciences, 14220 Prague, Czech Republic
3
Department of Computer Science, Czech Technical University in Prague, 12135 Prague, Czech Republic
4
Department of Environmental Analytical Chemistry, Institute of Analytical Chemistry of the Czech Academy of Sciences, 60200 Brno, Czech Republic
5
Department of Chemistry and Toxicology, Veterinary Research Institute, 62100 Brno, Czech Republic
*
Author to whom correspondence should be addressed.
Nanomaterials 2020, 10(3), 550; https://doi.org/10.3390/nano10030550
Received: 20 February 2020 / Revised: 12 March 2020 / Accepted: 17 March 2020 / Published: 18 March 2020
(This article belongs to the Special Issue Lung Cell Toxicity of Metal-containing Nanoparticles)
We investigated the transcriptomic response and epigenetic changes in the lungs of mice exposed to inhalation of copper(II) oxide nanoparticles (CuO NPs) (8 × 105 NPs/m3) for periods of 3 days, 2 weeks, 6 weeks, and 3 months. A whole genome transcriptome and miRNA analysis was performed using next generation sequencing. Global DNA methylation was assessed by ELISA. The inhalation resulted in the deregulation of mRNA transcripts: we detected 170, 590, 534, and 1551 differentially expressed transcripts after 3 days, 2 weeks, 6 weeks, and 3 months of inhalation, respectively. Biological processes and pathways affected by inhalation, differed between 3 days exposure (collagen formation) and longer treatments (immune response). Periods of two weeks exposure further induced apoptotic processes, 6 weeks of inhalation affected the cell cycle, and 3 months of treatment impacted the processes related to cell adhesion. The expression of miRNA was not affected by 3 days of inhalation. Prolonged exposure periods modified miRNA levels, although the numbers were relatively low (17, 18, and 38 miRNAs, for periods of 2 weeks, 6 weeks, and 3 months, respectively). Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways analysis based on miRNA–mRNA interactions, revealed the deregulation of processes implicated in the immune response and carcinogenesis. Global DNA methylation was not significantly affected in any of the exposure periods. In summary, the inhalation of CuO NPs impacted on both mRNA and miRNA expression. A significant transcriptomic response was already observed after 3 days of exposure. The affected biological processes and pathways indicated the negative impacts on the immune system and potential role in carcinogenesis. View Full-Text
Keywords: copper(II) oxide nanoparticles; inhalation; mouse; gene expression; DNA methylation copper(II) oxide nanoparticles; inhalation; mouse; gene expression; DNA methylation
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Rossner, P., Jr.; Vrbova, K.; Rossnerova, A.; Zavodna, T.; Milcova, A.; Klema, J.; Vecera, Z.; Mikuska, P.; Coufalik, P.; Capka, L.; Krumal, K.; Docekal, B.; Holan, V.; Machala, M.; Topinka, J. Gene Expression and Epigenetic Changes in Mice Following Inhalation of Copper(II) Oxide Nanoparticles. Nanomaterials 2020, 10, 550.

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