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Table 1 Global and gene-specific DNA methylation alterations induced by various nanoparticles

From: Epigenetic Effects of Nanomaterials and Nanoparticles

Nanomaterials (NMs) and Nanoparticles (NPs) In vitro or in vivo Experimental design Epigenetic effect Reference
Carbon nanotubes (CNTs); single-walled and multi-walled carbon nanotubes (SWCNTs, MWCNTs) In vitro Human THP-1 monocytes exposed to 25 and 100 µg/mL of SWCNTs and MWCNTs for 24 h No difference in global DNA methylation (5-mC) or DNA hydroxymethylation (5-hmC)
Hypomethylation of 1127 genes, including STAT5A, JAK3-STAT6, VEGFA, NOTCH1, NOTCH4, NOSS, WNT5B, PRKCZ, SH2D2A, SFRP1, FGFR1, TF, NAP2K2, AKT1, MEIS1
[15]
CNTs: SWCNTs, MWCNTs In vitro Human bronchial epithelial cells 16HBE exposed to 25 and 100 µg/mL of SWCNTs and MWCNTs for 24 h No difference in global DNA methylation (5-mC) or DNA hydroxymethylation (5-hmC)
Hypomethylation of 2398 genes. Hypomethylation of individual CpG sites in 501 genes residing in the gene body and promoter regions, including SKI, GSTP1, SHROOM2, NF1, AKP8L, FOXK2, EIF4E
[16]
CNTs: SWCNTs, MWCNTs In vitro Human bronchial epithelial cells (16HBE) were treated with 0.25 μg/mL of MWCNTs or SWCNTs for four weeks (sub-chronic exposure) followed by two weeks of no particle exposure (recovery period) No difference in global DNA methylation (5-mc)
Hypermethylation of HPCAL1, PRSS3, KLK3, KLF3 genes in SWCNT-exposed cells
[17]
CNTs: SWCNTs, MWCNTs In vitro Human bronchial epithelial cells 16HBE exposed to 25 and 100 µg/mL of SWCNTs and MWCNTs for 24 h No difference in global DNA methylation (5-mC) or DNA hydroxymethylation (5-hmC)
Differentially methylated for MWCNTs:
HDAC4, MAP3K10
Differentially methylated for SWCNTs:
MYO1C, NPAT/ATM, DNMT1
Differentially methylated for SWCNTs and MWCNTs: PIC3R2
Hypermethylation of ATM/NPAT promoter
[18]
CNTs: SWCNTs, MWCNTs In vitro Human bronchial epithelial cells 16HBE exposed to 25 and 100 µg/mL of SWCNTs and MWCNTs for 24 h MWCNTs induced significant dose-dependent loss of DNA methylation [19]
Carbon dots (CDs) In vitro Human embryonic lung fibroblasts HEL12469 exposed to 10-500 µg/mL of positively or negatively charged CDs for 24 h No difference in global DNA methylation (5-mC) [20]
CNTs: MWCNTs In vivo Workers (n = 24) occupationally exposed to the MWCNTs and unexposed controls (n = 43) for 7 days No difference in global DNA methylation (5-mC) or DNA hydroxymethylation (5-hmC)
Changes at individual CpG sites in the promoter region of DNMT1, ATM, SKI, HDAC4
[46]
CNTs: MWCNTs In vivo C57BLJ6 mice were exposed to 25 µl of MWCNTs suspension containing 50 µg of nanoparticles by a single oropharyngeal instillation, and solution was aspirated into the lungs. First effects were observed after 7 days, and mice were euthanized Genomic hypomethylation in lung tissue and blood.
Decrease in EFN-ɣ methylation
TNF-α promotor hypomethylation
Increase of methylation in Thy-1 promotor
[38]
Carbon nanoparticles (CNPs) In vivo Adult zebrafish (Danio rerio) were randomly allocated into three separate tanks with 3 L of 0, 10 and 30 μg/mL CNPs suspensions for 60 days Upregulation of dnmt3b and Tet2 in heart tissue
Dose‐dependent decreases in the mRNA expression
of dnmt1, dnmt3a, and Tet1
Promoter demethylation of
lebp, cd248b, and il11
Increase in transcriptions for lebp and cd248b in the high‐dose group
[40]
Modified Nano-Graphene quantum nanodots (M-GQDs) In vivo Zebrafish were exposed to 2, 10, and 50 mg/L modified reduced, hydroxylated, or aminated nano-graphene quantum dots for 7 days Global DNA hypermethylation (tissue -specific and dose-dependent) [41]
Laser printer-emitted nanoparticles In vivo Single intra-tracheal instillation of 2.5 mg/kg body weight of laser printer-emitted engineered nanoparticles into BALB/c mice: after 24 h, lung tissue was analyzed Increase in global level of 5-meC by 25% and 5-hmeC by 50% [39]
Silica NPs (SiO2-NPs) In vitro Human HaCaT cells exposed to 2.5-10 µg/mL SiO2-NPs for 24 h Global DNA hypomethylation
Dose-dependent decrease of the levels of DNMT1, DNMT3A, and methyl GpG binding protein 2 (MBD2)
[21]
SiO2-NPs In vitro Mouse Bhas 42 cells exposed to 15 or 25 µg/cm2 of the crystalline silica particles Min-U-Sil® 5 for 48 h ~80% decrease in global DNA methylation
Increase in the levels of DNMT3A and DNMA3B
[22]
SiO2-NPs In vitro Human HaCaT cells exposed to 10 µg/mL and 100 µg/mL of SiO2-NPs for 24 h Reduced methylation of Alu repetitive elements [23]
SiO2-NPs In vitro Human HaCaT cells exposed to10 µg/mL SiO2-NPs for 24 h Promoter hypermethylation and decreased expression of PARP1 protein [24]
SiO2-NPs In vitro Human bronchial epithelial cells BEAS-2B exposed to SiO2-NPs at 5 µg/mL for 30 passages (prolonged exposure) Global DNA hypermethylation: 1973 hypermethylated CpG loci over 223 hypomethylated CpG loci.
Hypermethylation of
CREB3L1 and Bcl-2 gene promoters
[25]
SiO2-NPs In vivo 31 workers from nanomaterial manufacturing and/or handling factories in Taiwan exposed to SiO2-NPs Global DNA hypomethylation [44]
SiO2-NPs in vivo White blood cells of 20 workers with long-term occupational exposure (mean time 14.5 years) to nanocomposite materials containing up to 20% SiO2-NPs Long-term exposure caused changes in CpG methylation:
341 CpG sites hypomethylated
364 CpG sites -hypomethylated
Short-term exposure did not affect DNA methylation patterns
[47]
Titanium dioxide nanoparticles (TiO2-NPs) In vitro Human MRC5 lung fibroblasts exposed to TiO2-NPs at 0.5 or 4 µg/mL for 24 and 48 h Global DNA hypomethylation
Decrease in total DNA methyltransferase activity
[26]
TiO2 -NPs In vitro Human lung epithelial cell line A549 exposed to silica or citrate coated TiO2-NPs and benchmark material P25 at
40 µg/cm2 for 48 and 72 h
Global DNA hypomethylation
Demethylation of LINE1 repetitive elements
[27]
TiO2-NPs In vitro Human small airway epithelial cells exposed to TiO2-NPs at 0.5 and 30 µg/mL for 24 h Demethylation of SINE B1 repetitive elements [28]
TiO2-NPs In vitro Human cell lines: skin (A-431), lung (NL20), liver (HepG2), and colon (CaCo-2) exposed to TiO2-NPs at 100 µg/mL for 24 and 72 h Global DNA hypomethylation in Caco-2, HepG2, and A-431 cells
Increase in methylation of CDKN1A, DNAJC15, GADD45A, GDF15, INSIG1, SCARA3, TP53, and BNIP3 genes
Altered expression of DNMT1, DNMT3A, DNMT3B, MBD2, and UHRF genes
[29]
Gold nanoparticles (Au-NPs) In vitro Human kidney embryonic HEK293 cells exposed to 100 µg/mL of Au-NPs for 72 h Global DNA hypomethylation [23]
Au-NPs In vitro Normal human skin fibroblasts and human skin melanoma cells A375 exposed to Au-NPs at 62.5 µg/mL for 24 and 48 h Global DNA hypomethylation [30]
Au-NPs In vitro Human breast cancer cells SK-BR-3 exposed to Au-NPs at concentration of 3 µg/mL for 24, 48, and 72 h No effect on global DNA methylation [31]
Au-NPs In vitro Human hepatic HepG2 cells exposed to 10 µg/mL for 24 h No effect on global DNA methylation [32]
Au-NPs In vitro MRC5 human fetal fibroblasts exposed to 1 nM concentration of AuNPs for 48 and 72 h No effect on global DNA methylation [33]
Au-NPs In vivo Intratracheal administration of 5-, 60- and 250-nm Au-NPs at 2.5 and 0.25 mg/mL for 48 h to BALB/c mice No effect on global DNA methylation and DNA hydroxymethylation
Promotor hypermethylation in Atm, Cdk, and Gsr genes
in mouse lung tissue
Promotor hypomethylation in Gpx gene in mouse lung tissue
[42]
Silver nanoparticles (Ag-NPs) In vitro HT22 mouse hippocampal neuronal cell line exposed to 1-20 µg/mL of Ag-NPs for 48 h Increase in DNA methyltransferases DNMT1, DNMT3A, and DNMT3B [34]
Ag-NPs In vitro Human BEAS-2B cell line was exposed to 1 µg/mL Ag-NPs for 6 weeks Marginal effects on DNA methylation: one differentially methylated gene promoter, corresponding to a gene (ENSG00000250358), 6 differentially methylated CpG sites and 5 differentially methylated tiling regions [36]
Ag-NPs In vitro Human lung adenocarcinoma epithelial cells A549, exposed to 10-200 µg/mL Ag-NPs for 48 and 72 h Global DNA hypermethylation [35]
Ag-NPs
Au-NPs
Magnetite
(Fe3O4) SPIONs
In vitro Human hepatic cell line HepG2 treated with10 µg/mL Ag-NPs, 10 µg/mL Au-NPs, 5 µg/mL SPIONs for 24 h No changes in promoter methylation of genes related to inflammation and apoptosis for any type of NPs studied [32]
Zinc oxide nanoparticles (ZnO-NPs) In vitro Human MRC5 lung fibroblasts exposed to ZnO-NPs at 4 or 8 µg/mL for 24 and 48 h Global DNA hypomethylation
Decrease in total DNA methyltransferase activity
[26]
ZnO-NPs In vitro Human embryonic kidney cells HEK293 exposed to ZnO-NPs at 25 or 50 µg/mL for 48 h Global DNA (5-mC) hypomethylation
Increase in DNA hydroxymethylation (5-hmC) associated with increased expression of TET1 and TET2 genes
[37]
Copper (II) oxide NPs (CuO-NPs) In vivo Male BALB/c mice were exposed to a single intra-tracheal instillation of 2.5 mg/kg body weight of copper (II) oxide (CuO)-NPs and lung tissue collected after 24 h of exposure Global DNA hypermethylation
Reduced expression of DNA methyltrasferases, Dnmt1, Dnmt3a, and DNMT3b, and Tet1
[39]
CuO-NPs In vivo Female ICR mice were exposed to 8x105 CuO-NPs in a whole-body inhalation chamber for either 3 days, 2 and 6 weeks, or 3 months No changes in global DNA methylation [43]