Epigenetic modulation upon exposure of lung fibroblasts to TiO2 and ZnO nanoparticles: alterations in DNA methylation

Nayana A Patil,1,2 WN Gade,2 Deepti D Deobagkar1 1Department of Zoology, Molecular Biology Research Laboratory, Centre of Advanced Studies, 2Department of Biotechnology, Proteomic Research Laboratory, Savitribai Phule Pune University, Pune, India Abstract: Titanium dioxide (TiO2) and zinc oxide (ZnO...

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Autores principales:	Patil NA, Gade WN, Deobagkar DD
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2016
Materias:	Nanotoxicity Epigenetics global DNA methylation 5mC DNA Methyltransferase Dnmt Cytosine methylation Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/0ba40d6a84354953a1ea3e23ead0f363
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spelling	oai:doaj.org-article:0ba40d6a84354953a1ea3e23ead0f3632021-12-02T06:33:28ZEpigenetic modulation upon exposure of lung fibroblasts to TiO2 and ZnO nanoparticles: alterations in DNA methylation1178-2013https://doaj.org/article/0ba40d6a84354953a1ea3e23ead0f3632016-09-01T00:00:00Zhttps://www.dovepress.com/epigenetic-modulation-upon-exposure-of-lung-fibroblasts-to-tio2-and-zn-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Nayana A Patil,1,2 WN Gade,2 Deepti D Deobagkar1 1Department of Zoology, Molecular Biology Research Laboratory, Centre of Advanced Studies, 2Department of Biotechnology, Proteomic Research Laboratory, Savitribai Phule Pune University, Pune, India Abstract: Titanium dioxide (TiO2) and zinc oxide (ZnO) nanoparticles (NPs) are promising candidates for numerous applications in consumer products. This will lead to increased human exposure, thus posing a threat to human health. Both these types of NPs have been studied for their cell toxicity, immunotoxicity, and genotoxicity. However, effects of these NPs on epigenetic modulations have not been studied. Epigenetics is an important link in the genotype and phenotype modulation and misregulation can often lead to lifestyle diseases. In this study, we have evaluated the DNA methylation-based epigenetic changes upon exposure to various concentrations of NPs. The investigation was designed to evaluate global DNA methylation, estimating the corresponding methyltransferase activity and expression of Dnmt gene using lung fibroblast (MRC5) cell line as lungs are the primary route of entry and target of occupational exposure to TiO2 and ZnO NPs. Enzyme-linked immunosorbent assay-based immunochemical assay revealed dose-related decrease in global DNA methylation and DNA methyltransferase activity. We also found direct correlation between the concentration of NPs, global methylation levels, and expression levels of Dnmt1, 3A, and 3B genes upon exposure. This is the first study to investigate effect of exposure to TiO2 and ZnO on DNA methylation levels in MRC5 cells. Epigenetic processes are known to play an important role in reprogramming and adaptation ability of an organism and can have long-term consequences. We suggest that changes in DNA methylation can serve as good biomarkers for early exposure to NPs since they occur at concentrations well below the sublethal levels. Our results demonstrate a clear epigenetic alteration in response to metal oxide NPs and that this effect was dose-dependent. Keywords: nanotoxicity, epigenetics, global DNA methylation, 5-mC, DNA methyltransferase, DnmtPatil NAGade WNDeobagkar DDDove Medical PressarticleNanotoxicityEpigeneticsglobal DNA methylation5mCDNA MethyltransferaseDnmtCytosine methylationMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 11, Pp 4509-4519 (2016)
institution	DOAJ
collection	DOAJ
language	EN
topic	Nanotoxicity Epigenetics global DNA methylation 5mC DNA Methyltransferase Dnmt Cytosine methylation Medicine (General) R5-920
spellingShingle	Nanotoxicity Epigenetics global DNA methylation 5mC DNA Methyltransferase Dnmt Cytosine methylation Medicine (General) R5-920 Patil NA Gade WN Deobagkar DD Epigenetic modulation upon exposure of lung fibroblasts to TiO2 and ZnO nanoparticles: alterations in DNA methylation
description	Nayana A Patil,1,2 WN Gade,2 Deepti D Deobagkar1 1Department of Zoology, Molecular Biology Research Laboratory, Centre of Advanced Studies, 2Department of Biotechnology, Proteomic Research Laboratory, Savitribai Phule Pune University, Pune, India Abstract: Titanium dioxide (TiO2) and zinc oxide (ZnO) nanoparticles (NPs) are promising candidates for numerous applications in consumer products. This will lead to increased human exposure, thus posing a threat to human health. Both these types of NPs have been studied for their cell toxicity, immunotoxicity, and genotoxicity. However, effects of these NPs on epigenetic modulations have not been studied. Epigenetics is an important link in the genotype and phenotype modulation and misregulation can often lead to lifestyle diseases. In this study, we have evaluated the DNA methylation-based epigenetic changes upon exposure to various concentrations of NPs. The investigation was designed to evaluate global DNA methylation, estimating the corresponding methyltransferase activity and expression of Dnmt gene using lung fibroblast (MRC5) cell line as lungs are the primary route of entry and target of occupational exposure to TiO2 and ZnO NPs. Enzyme-linked immunosorbent assay-based immunochemical assay revealed dose-related decrease in global DNA methylation and DNA methyltransferase activity. We also found direct correlation between the concentration of NPs, global methylation levels, and expression levels of Dnmt1, 3A, and 3B genes upon exposure. This is the first study to investigate effect of exposure to TiO2 and ZnO on DNA methylation levels in MRC5 cells. Epigenetic processes are known to play an important role in reprogramming and adaptation ability of an organism and can have long-term consequences. We suggest that changes in DNA methylation can serve as good biomarkers for early exposure to NPs since they occur at concentrations well below the sublethal levels. Our results demonstrate a clear epigenetic alteration in response to metal oxide NPs and that this effect was dose-dependent. Keywords: nanotoxicity, epigenetics, global DNA methylation, 5-mC, DNA methyltransferase, Dnmt
format	article
author	Patil NA Gade WN Deobagkar DD
author_facet	Patil NA Gade WN Deobagkar DD
author_sort	Patil NA
title	Epigenetic modulation upon exposure of lung fibroblasts to TiO2 and ZnO nanoparticles: alterations in DNA methylation
title_short	Epigenetic modulation upon exposure of lung fibroblasts to TiO2 and ZnO nanoparticles: alterations in DNA methylation
title_full	Epigenetic modulation upon exposure of lung fibroblasts to TiO2 and ZnO nanoparticles: alterations in DNA methylation
title_fullStr	Epigenetic modulation upon exposure of lung fibroblasts to TiO2 and ZnO nanoparticles: alterations in DNA methylation
title_full_unstemmed	Epigenetic modulation upon exposure of lung fibroblasts to TiO2 and ZnO nanoparticles: alterations in DNA methylation
title_sort	epigenetic modulation upon exposure of lung fibroblasts to tio2 and zno nanoparticles: alterations in dna methylation
publisher	Dove Medical Press
publishDate	2016
url	https://doaj.org/article/0ba40d6a84354953a1ea3e23ead0f363
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_version_	1718399855411331072

Epigenetic modulation upon exposure of lung fibroblasts to TiO2 and ZnO nanoparticles: alterations in DNA methylation

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