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

0532898 - ÚEM 2022 RIV CH eng J - Journal Article
Rössner ml., Pavel - Vrbová, Kristýna - Rössnerová, Andrea - Závodná, Táňa - Milcová, Alena - Kléma, J. - Večeřa, Zbyněk - Mikuška, Pavel - Coufalík, Pavel - Čapka, Lukáš - Křůmal, Kamil - Dočekal, Bohumil - Holáň, Vladimír - Machala, M. - Topinka, Jan
Gene Expression and Epigenetic Changes in Mice Following Inhalation of Copper(II) Oxide Nanoparticles.
Nanomaterials. Roč. 10, č. 3 (2020), č. článku 550. E-ISSN 2079-4991
R&D Projects: GA MŠMT(CZ) LO1508; GA ČR(CZ) GBP503/12/G147
Institutional support: RVO:68378041 ; RVO:68081715
Keywords : copper(II) oxide nanoparticles * inhalation * mouse
OECD category: Genetics and heredity (medical genetics to be 3); Organic chemistry (UIACH-O)
Impact factor: 5.076, year: 2020
Method of publishing: Open access
https://www.mdpi.com/2079-4991/10/3/550

We investigated the transcriptomic response and epigenetic changes in the lungs of mice exposed to inhalation of copper(II) oxide nanoparticles (CuO NPs) (8 x 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.
Permanent Link: http://hdl.handle.net/11104/0311273