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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Main Authors: Patil NA, Gade WN, Deobagkar DD
Format: Article
Language:English
Published: Dove Medical Press 2016-09-01
Series:International Journal of Nanomedicine
Subjects:
5mC
Online Access:https://www.dovepress.com/epigenetic-modulation-upon-exposure-of-lung-fibroblasts-to-tio2-and-zn-peer-reviewed-article-IJN
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spelling doaj-0ba40d6a84354953a1ea3e23ead0f3632020-11-25T00:33:06ZengDove Medical PressInternational Journal of Nanomedicine1178-20132016-09-01Volume 114509451928792Epigenetic modulation upon exposure of lung fibroblasts to TiO2 and ZnO nanoparticles: alterations in DNA methylationPatil NAGade WNDeobagkar DDNayana 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, Dnmthttps://www.dovepress.com/epigenetic-modulation-upon-exposure-of-lung-fibroblasts-to-tio2-and-zn-peer-reviewed-article-IJNNanotoxicityEpigeneticsglobal DNA methylation5mCDNA MethyltransferaseDnmtCytosine methylation
collection DOAJ
language English
format Article
sources DOAJ
author Patil NA
Gade WN
Deobagkar DD
spellingShingle Patil NA
Gade WN
Deobagkar DD
Epigenetic modulation upon exposure of lung fibroblasts to TiO2 and ZnO nanoparticles: alterations in DNA methylation
International Journal of Nanomedicine
Nanotoxicity
Epigenetics
global DNA methylation
5mC
DNA Methyltransferase
Dnmt
Cytosine methylation
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
series International Journal of Nanomedicine
issn 1178-2013
publishDate 2016-09-01
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
topic Nanotoxicity
Epigenetics
global DNA methylation
5mC
DNA Methyltransferase
Dnmt
Cytosine methylation
url https://www.dovepress.com/epigenetic-modulation-upon-exposure-of-lung-fibroblasts-to-tio2-and-zn-peer-reviewed-article-IJN
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