DNA Methylation Alterations Induced By Transient Exposure of MCF-7 Cells to Maghemite Nanoparticles

Bonadio, Raphael Severino; Arcanjo, Ana Carolina; Lima, Emília C D; Vasconcelos, Alline T; Silva, Renata C.; Horst, Frederico Hillesheim; Azevedo, Ricardo Bentes; Poças-Fonseca, Marcio José; Longo, João Paulo Figueiró

doi:10.2217/nnm-2017-0241

Cited by 4 publications

(5 citation statements)

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“…The only report concerning the impact of AuNPs on DNA methylation shows the induction of methylation of several genes in mouse lungs in vivo [17]. Similarly, the only report regarding SPIONs’ impact on DNA methylation shows that maghemite (γ-Fe 2 O 3 ) nanoparticles did not affect global DNA methylation in MCF-7 cells, but affect the methylation of several specific genes [33]. It seems that the impact of nanoparticles on DNA methylation is cell-type-specific and highly dependent on the properties of the nanomaterial.…”

Section: Discussionmentioning

confidence: 99%

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Silver, Gold, and Iron Oxide Nanoparticles Alter miRNA Expression but Do Not Affect DNA Methylation in HepG2 Cells

2019

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The increasing use of nanoparticles (NPs) in various applications entails the need for reliable assessment of their potential toxicity for humans. Originally, studies concerning the toxicity of NPs focused on cytotoxic and genotoxic effects, but more recently, attention has been paid to epigenetic changes induced by nanoparticles. In the present research, we analysed the DNA methylation status of genes related to inflammation and apoptosis as well as the expression of miRNAs related to these processes in response to silver (AgNPs), gold (AuNPs), and superparamagnetic iron oxide nanoparticles (SPIONs) at low cytotoxic doses in HepG2 cells. There were no significant differences between treated and control cells in the DNA methylation status. We identified nine miRNAs, the expression of which was significantly altered by treatment with nanoparticles. The highest number of changes was induced by AgNPs (six miRNAs), followed by AuNPs (four miRNAs) and SPIONs (two miRNAs). Among others, AgNPs suppressed miR-34a expression, which is of particular interest since it may be responsible for the previously observed AgNPs-mediated HepG2 cells sensitisation to tumour necrosis factor (TNF). Most of the miRNAs affected by NP treatment in the present study have been previously shown to inhibit cell proliferation and tumourigenesis. However, based on the observed changes in miRNA expression we cannot draw definite conclusions regarding the pro- or anti-tumour nature of the NPs under study. Further research is needed to fully elucidate the relation between observed changes in miRNA expression and the effect of NPs observed at the cellular level. The results of the present study support the idea of including epigenetic testing during the toxicological assessment of the biological interaction of nanomaterials.

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Section: Discussionmentioning

confidence: 99%

“…On the other hand, literature on the epigenetic effects of SPIONs is very limited. It has been reported that Fe 2 O 3 SPIONs affect miRNA expression in NIH/3T3 cells [9] and DNA methylation in MCF-7 cells [33]. Epigenetic effects of Fe 3 O 4 SPIONs have not been studied so far.…”

Section: Introductionmentioning

confidence: 99%

Silver, Gold, and Iron Oxide Nanoparticles Alter miRNA Expression but Do Not Affect DNA Methylation in HepG2 Cells

2019

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“…The authors concluded that short-term exposure to engineered NM modestly affected DNA methylation within the most abundant transposable elements [7]. A detailed DNA methylation profile of DNA methyltransferase genes in breast cancer cell line MCF-7 after treatment with maghemite nanoparticles revealed epigenetic changes, even though the overall percentage of DNA methylation was not affected [8], which in contrast to altered global methylation by the same nanomaterial but in human submandibular gland cells, which was analyzed in a later study [9]. No significant differences in the DNA methylation status of inflammatory and apoptosis response genes of human liver cancer cells (HepG2) was found after silver, gold and superparamagnetic iron nanoparticle (SPION) exposure [10].…”

Section: Introductionmentioning

confidence: 99%

DNA Methylation Profiles in a Group of Workers Occupationally Exposed to Nanoparticles

Rössnerová

Hoňková

Pelclová

et al. 2020

IJMS

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The risk of exposure to nanoparticles (NPs) has rapidly increased during the last decade due to the vast use of nanomaterials (NMs) in many areas of human life. Despite this fact, human biomonitoring studies focused on the effect of NP exposure on DNA alterations are still rare. Furthermore, there are virtually no epigenetic data available. In this study, we investigated global and gene-specific DNA methylation profiles in a group of 20 long-term (mean 14.5 years) exposed, nanocomposite, research workers and in 20 controls. Both groups were sampled twice/day (pre-shift and post-shift) in September 2018. We applied Infinium Methylation Assay, using the Infinium MethylationEPIC BeadChips with more than 850,000 CpG loci, for identification of the DNA methylation pattern in the studied groups. Aerosol exposure monitoring, including two nanosized fractions, was also performed as proof of acute NP exposure. The obtained array data showed significant differences in methylation between the exposed and control groups related to long-term exposure, specifically 341 CpG loci were hypomethylated and 364 hypermethylated. The most significant CpG differences were mainly detected in genes involved in lipid metabolism, the immune system, lung functions, signaling pathways, cancer development and xenobiotic detoxification. In contrast, short-term acute NP exposure was not accompanied by DNA methylation changes. In summary, long-term (years) exposure to NP is associated with DNA epigenetic alterations.

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“…Moreover, citrate detachment from the surface of MNPs under physiological conditions is negligible, and the physical-chemical characteristics of citrate-capped MNPs can be preserved over years. 21,27 Indeed, previous in vivo investigations have shown the biocompatibility and nonmutagenic effects of citrate coatings, [28][29][30] in spite of adverse effects described in in vitro tests. 31 However, citrate-coated MNPs can be colloidally unstable in a biological system when dispersed in a medium with high ionic strength, such as PBS buffer.…”

Section: Discussionmentioning

confidence: 99%

<p>The influence of female mice age on biodistribution and biocompatibility of citrate-coated magnetic nanoparticles</p>

Pinheiro

Fascineli

Farias

et al. 2019

IJN

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Background: Magnetic nanoparticles (MNPs) have been successfully tested for several purposes in medical applications. However, knowledge concerning the effects of nanostructures on elderly organisms is remarkably scarce. Purpose: To fill part of this gap, this work aimed to investigate biocompatibility and biodistribution aspects of magnetic nanoparticles coated with citrate (NpCit) in both elderly and young healthy mice. Methods: NpCit (2.4 mg iron) was administered intraperitoneally, and its toxicity was evaluated for 28 days through clinical, biochemical, hematological, and histopathological examinations. In addition, its biodistribution was evaluated by spectrometric (inductively coupled plasma optical emission spectrometry) and histological methods. Results: NpCit presented age-dependent effects, inducing very slight and temporary biochemical and hematological changes in young animals. These changes were even weaker than the effects of the aging process, especially those related to the hematological data, tumor necrosis factor alpha, and nitric oxide levels. On the other hand, NpCit showed a distinct set of results in the elderly group, sometimes reinforcing (decrease of lymphocytes and increase of monocytes) and sometimes opposing (erythrocyte parameters and cytokine levels) the aging changes. Leukocyte changes were still observed on the 28th day after treatment in the elderly group. Slight evidence of a decrease in liver and immune functions was detected in elderly mice treated or not treated with NpCit. It was noted that tissue damage or clinical changes related to aging or to the NpCit treatment were not observed. As detected for aging, the pattern of iron biodistribution was significantly different after NpCit administration: extra iron was detected until the 28th day, but in different organs of elderly (liver and kidneys) and young (spleen, liver, and lungs) mice. Conclusion: Taken together, the data show NpCit to be a stable and reasonably biocompatible sample, especially for young mice, and thus appropriate for biomedical applications. The data showed important differences after NpCit treatment related to the animals' age, and this emphasizes the need for further studies in older animals to appropriately extend the benefits of nanotechnology to the elderly population.

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DNA Methylation Alterations Induced By Transient Exposure of MCF-7 Cells to Maghemite Nanoparticles

Abstract: Transient exposure to MNP-CIT promoted epigenomic changes and altered the DNMT genes regulation in MCF-7 cells. These events should be considered for biomedical applications.

Cited by 4 publications

References 67 publications

Silver, Gold, and Iron Oxide Nanoparticles Alter miRNA Expression but Do Not Affect DNA Methylation in HepG2 Cells

Silver, Gold, and Iron Oxide Nanoparticles Alter miRNA Expression but Do Not Affect DNA Methylation in HepG2 Cells

DNA Methylation Profiles in a Group of Workers Occupationally Exposed to Nanoparticles

<p>The influence of female mice age on biodistribution and biocompatibility of citrate-coated magnetic nanoparticles</p>

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