SiO2 nanoparticles induce global genomic hypomethylation in HaCaT cells

Gong, Chunmei; Tao, Guanhong; Liu, Yang; Liu, Jing; Liu, Qingchen; Zhuang, Zhixiong

doi:10.1016/j.bbrc.2010.05.076

Cited by 119 publications

(93 citation statements)

References 13 publications

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“…It was observed that with increasing silica nanoparticle doses, the global level of mRNA expression of MBDs gradually decreased. The level of DNA MTase in normal human keratinocytes has changed in the same way which resulted in a decrease of genomic DNA methylation status [65]. CdTe (cadmium telluride) QDs can bind to core histones and the positively charged histones can change the charge and the size of negatively charged QDs which in turn cause an increase in nanoparticle size from 4 to 150 nm and in the NPs charge from −28.9 mV to +15 mV and stimulate aggregate formation [66].…”

Section: Epigenetic Toxicity Of Npsmentioning

confidence: 99%

Nanoparticle Technology as a Double-Edged Sword: Cytotoxic, Genotoxic and Epigenetic Effects on Living Cells

Jennifer¹,

Wnuk²

2013

JBNB

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Nanoparticles are considered as powerful tools in nanotechnological applications. Due to their unique physicochemical properties, their interactions with different biological systems have been shown. Nanomaterials have been successfully used as coating materials or treatment and diagnosis tools. Nevertheless, toxic effects of nanoparticles in vitro and in vivo have also been reported. Here, we summarize the current state of knowledge on exposure routes, cellular uptake and toxicological activities of the commonly used nanoparticles. In this context, we discuss the mechanisms of toxicity of nanoparticles involving perturbation of redox milieu homeostasis and cellular signaling pathways.

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Section: Epigenetic Toxicity Of Npsmentioning

confidence: 99%

Nanoparticle Technology as a Double-Edged Sword: Cytotoxic, Genotoxic and Epigenetic Effects on Living Cells

Jennifer¹,

Wnuk²

2013

JBNB

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“…Second, living systems are self-organized, complex adaptive systems (CAS) or networks with nonlinear dynamics and emergent properties that are not predicted by understanding the properties of their component parts [60,87,88]. NPs can both readily translocate around the organism and set cascades of biological signaling into motion, e.g., via activating exosome release [80,89], inflammasome proteins and cytokines [65,77], and epigenetic modulation [90,91]. As a result, nano-drugs and natural products can elicit changes in cells and distant parts of an organism not obvious from a bulk medicine focus on only local inhibitory effects for specific symptoms [69].…”

Section: Recipient Organisms As Self-organized Complex Adaptive Networkmentioning

confidence: 99%

Nonlinear Response Amplification Mechanisms for Low Doses of Natural Product Nanomedicines: Dynamical Interactions with the Recipient Complex Adaptive System

Bell

Sarter

Koithan

et al. 2013

J Nanomed Nanotechol

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The purpose of the present paper is (a) to outline the self-organized, complex adaptive network nature of the organism as recipient of nanomedicines; (b) to propose several nonlinear endogenous amplification processes by which pulsed low doses of traditional, homeopathically-manufactured natural product nanomedicines may stimulate a return toward healthier function; and (c) to discuss their potential relevance to novel, but safer than conventional dosing strategies for contemporary nanomedicines. Homeopathy is an over 200-year-old system of complementary and alternative medicine (CAM) that uses low doses of natural plant-, mineral-, and animal-sourced nanomedicines. Homeopathic manufacturing is "green", with mechanical grinding in lactose and agitation in ethanol-water as primary reagents. Agitation within glass containers at room temperature may also contribute nanosilica and nanosilicon as drug delivery vehicles and biological amplifiers. The medicine selection is matched to the recipient organism's systemic patterns of dysfunction and pulsed in the timing of the discrete doses. Endogenous amplification processes within the recipient organism may involve hormesis, time-dependent sensitization, and/or stochastic resonance. Effects are adaptive and systemically diffuse, i.e., causally indirect, rather than pharmacological and local, i.e., direct. All of these nonlinear response processes require interaction of the nanoparticle (NP) dose with the organism as a complex adaptive system. The pulsed NP dose serves as a low intensity salient danger signal for the organism to make network-wide adaptive changes that can lead to healing. The historically safe therapeutic approach of homeopathic nanomedicine dosing avoids risks of high, continuous doses and cumulative toxicity that contemporary nanomedicine researchers are now trying to solve while using NPs as if they were conventional bulk drugs. Integrating the insights, technical procedures, and clinical dosing approaches from modern and homeopathic nanomedicine could lead to major advances in the field for more effective and safer translational applications.NPs in homeopathic medicines [3]. NP concentrations are low, but measurable [3]. Like modern manufactured NPs [13], homeopathicallymanufactured medicines in solution also can exhibit aging effects [9,14]. These nanomedicines are delivered either in ethanolic liquids or sprayed and dried onto lactose or lactose/sucrose pellets for oral administration.Homeopathic manufacturing materials and methods are inherently "green" [15,16]. Previous papers have addressed the striking similarities between modern top-down mechanical attrition procedures for making nanoparticles (NPs) [17] and historical homeopathic medicine manufacturing methods and materials [15,[18][19][20][21]. These similarities include mechanically grinding source materials in lactose for hours and repeatedly agitating ethanol-water solutions containing the source Citation: Bell IR, Sarter B, Koithan M, Standish LJ, Banerji P, et al. (2013) Nonlinea...

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“…For example, cadmium telluride quantum dots and silica NPs are reported to affect global DNA methylation pattern, modulate DNA methyltransferase activity, methylCpG-binding domain (MBD) protein expression, and/or alter posttranslational modifications of histone proteins. [33][34][35] SiO 2 NP has been shown to decrease the messenger RNA (mRNA) expression of PARP-1, increase the DNA methylation levels of PARP-1 promoter, decrease global DNA methylation, and the related methyltransferase, including Dnmt1, Dnmt3A, and MBD2. 35,36 Similar study on silver NPs (AgNPs) shows that at sublethal levels AgNP can alter histone methylation, thereby effecting globin gene expression in red blood cells.…”

Section: Introductionmentioning

confidence: 99%

“…[33][34][35] SiO 2 NP has been shown to decrease the messenger RNA (mRNA) expression of PARP-1, increase the DNA methylation levels of PARP-1 promoter, decrease global DNA methylation, and the related methyltransferase, including Dnmt1, Dnmt3A, and MBD2. 35,36 Similar study on silver NPs (AgNPs) shows that at sublethal levels AgNP can alter histone methylation, thereby effecting globin gene expression in red blood cells. 37 Copper oxide and gold NPs are shown to induce alterations in miRNA expression.…”

Section: Introductionmentioning

confidence: 99%

“…Limited data suggest that exposure to some NPs, such as cadmium telluride quantum dots, SiO 2 , AgNP, gold NP, multiwalled carbon nanotubes, copper oxide, and engineered NPs adversely affect epigenetic landscape. [31][32][33][34][35][36][37][38][39][40][41] To our knowledge, global DNA methylation and Dnmt expression levels have not previously been investigated for TiO 2 and ZnO NP. Our results suggest that global hypomethylation is associated with concentration of NPs.…”

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confidence: 99%

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Epigenetic modulation upon exposure of lung fibroblasts to TiO<sub>2</sub> and ZnO nanoparticles: alterations in DNA methylation

Patil

Gade

Deobagkar

2016

IJN

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Titanium dioxide (TiO 2 ) 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 TiO 2 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 TiO 2 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.

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SiO2 nanoparticles induce global genomic hypomethylation in HaCaT cells

Cited by 119 publications

References 13 publications

Nanoparticle Technology as a Double-Edged Sword: Cytotoxic, Genotoxic and Epigenetic Effects on Living Cells

Nanoparticle Technology as a Double-Edged Sword: Cytotoxic, Genotoxic and Epigenetic Effects on Living Cells

Nonlinear Response Amplification Mechanisms for Low Doses of Natural Product Nanomedicines: Dynamical Interactions with the Recipient Complex Adaptive System

Epigenetic modulation upon exposure of lung fibroblasts to TiO<sub>2</sub> and ZnO nanoparticles: alterations in DNA methylation

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