Zinc-Oxide Nanoparticles Exhibit Genotoxic, Clastogenic, Cytotoxic and Actin Depolymerization Effects by Inducing Oxidative Stress Responses in Macrophages and Adult Mice

Pati, Rashmirekha; Das, Indrajit; Mehta, Ranjit K.; Sahu, Rojalin; Sonawane, Avinash

doi:10.1093/toxsci/kfw010

Cited by 119 publications

(67 citation statements)

References 74 publications

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“…Next, Vieira et al reported an alteration in cytoskeletal organization, including a change of cell polarity and the increase of F‐actin fiber formation, in HDF treated with AuNPs and AgNPs. Another result suggested that exposure of zinc oxide (ZnO) NPs to RAW 264.7 mouse macrophages resulted in F‐actin depolymerization and a decrease in the level of F‐actins . Fanarraga and co‐workers observed a reorganization of actin microfilaments into cell bundles and formation of aberrant F‐actin trails affecting proliferation and viability of human keratinocytes (HaCat) and cervical cancer cells (HeLa) after ZnO NPs treatment (Figure c).…”

Section: Effects Of Intracellular Nanoparticles On Adhesion Cytoskelmentioning

confidence: 94%

Nanoparticle–Cell Interaction: A Cell Mechanics Perspective

et al. 2018

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Progress in the field of nanoparticles has enabled the rapid development of multiple products and technologies; however, some nanoparticles can pose both a threat to the environment and human health. To enable their safe implementation, a comprehensive knowledge of nanoparticles and their biological interactions is needed. In vitro and in vivo toxicity tests have been considered the gold standard to evaluate nanoparticle safety, but it is becoming necessary to understand the impact of nanosystems on cell mechanics. Here, the interaction between particles and cells, from the point of view of cell mechanics (i.e., bionanomechanics), is highlighted and put in perspective. Specifically, the ability of intracellular and extracellular nanoparticles to impair cell adhesion, cytoskeletal organization, stiffness, and migration are discussed. Furthermore, the development of cutting-edge, nanotechnology-driven tools based on the use of particles allowing the determination of cell mechanics is emphasized. These include traction force microscopy, colloidal probe atomic force microscopy, optical tweezers, magnetic manipulation, and particle tracking microrheology.

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Section: Effects Of Intracellular Nanoparticles On Adhesion Cytoskelmentioning

confidence: 94%

Nanoparticle–Cell Interaction: A Cell Mechanics Perspective

et al. 2018

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“…Numerous in vitro and in vivo studies have demonstrated that ENMs have the potential to induce DNA damage (19–21). For instance, zinc oxide nanoparticles (ZnO NPs) have been shown to exhibit genotoxic, clastogenic and cytotoxic effects (123). Zinc oxide nanoparticles are highly important due to their current and potential applications in biosensors, sunscreens, cosmetics, medicine and nutrition amongst others (124).…”

Section: Modifications Of the Automated Fadu Assaymentioning

confidence: 99%

Emerging metrology for high-throughput nanomaterial genotoxicology

Nelson

Wright

Ibuki

et al. 2016

MUTAGE

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The rapid development of the engineered nanomaterial (ENM) manufacturing industry has accelerated the incorporation of ENMs into a wide variety of consumer products across the globe. Unintentionally or not, some of these ENMs may be introduced into the environment or come into contact with humans or other organisms resulting in unexpected biological effects. It is thus prudent to have rapid and robust analytical metrology in place that can be used to critically assess and/or predict the cytotoxicity, as well as the potential genotoxicity of these ENMs. Many of the traditional genotoxicity test methods [e.g. unscheduled DNA synthesis assay, bacterial reverse mutation (Ames) test, etc.,] for determining the DNA damaging potential of chemical and biological compounds are not suitable for the evaluation of ENMs, due to a variety of methodological issues ranging from potential assay interferences to problems centered on low sample throughput. Recently, a number of sensitive, high-throughput genotoxicity assays/platforms (CometChip assay, flow cytometry/micronucleus assay, flow cytometry/γ-H2AX assay, automated ‘Fluorimetric Detection of Alkaline DNA Unwinding’ (FADU) assay, ToxTracker reporter assay) have been developed, based on substantial modifications and enhancements of traditional genotoxicity assays. These new assays have been used for the rapid measurement of DNA damage (strand breaks), chromosomal damage (micronuclei) and for detecting upregulated DNA damage signalling pathways resulting from ENM exposures. In this critical review, we describe and discuss the fundamental measurement principles and measurement endpoints of these new assays, as well as the modes of operation, analytical metrics and potential interferences, as applicable to ENM exposures. An unbiased discussion of the major technical advantages and limitations of each assay for evaluating and predicting the genotoxic potential of ENMs is also provided.

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“…Many researchers have demonstrated that gold NPs exhibit less cytotoxic and genotoxic effects compared to other nanomaterials like Zn and Ag NPs 36,37 . However, research in Drosophila melanogaster reported the gold NPs induces decreased infertility and numbers of progeny, increased in aberrant phenotype 38 .…”

Section: Discussionmentioning

confidence: 99%

The nervous system is the major target for Gold nanoparticles: Evidence from RNA sequencing data of C. elegans

Sun

Yang

et al. 2019

Preprint

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12The increasing use of gold nanoparticles (NPs) raises concerns about the potential effect of gold NPs 13 exposure on human health. Therefore, gold NPs exposure is hard to evaluate at the organ level with 14 current measurement technology. The bio-distribution assay showed that intestine was the organ with 15 most gold NPs accumulated. However, our data indicated that 62.8% of the significant altered genes 16 were function in the nervous system using tissue enrichment analysis. Notably, gene ontology analysis 17 has demonstrated that NP exposure interfered with the development of animals. Furthermore, the 18 transcription factors DAF-16 and HSF-1 were regulating the oxidative stress genes induced by gold NPs. 19Therefore, we proposed the localization of the oxidative stress genes in the neuron cells and how their 20 expression affect neuron communication. Our results demonstrate that the gold NPs-induced oxidative 21 stress affects the nervous system via physical damage to the neurons and disruption of cell-to-cell 22 communication. Future toxicology research on gold NPs should focus on neurons. 23 24 25 26 55 Studies in mice show that 13 nm PEG-coated gold NPs were mainly deposited in the liver, kuffer cells, 56 and the spleen 21 . While other studies in rats proved 18 nm gold NPs were accumulated in the liver and 57 spleen, but 1.4 nm mainly in the kidney 22 . The intestine of C. elegans, have the combined function of 58 liver, spleen and kidney, accumulates most of the gold NPs 23 . Although these organs accumulate gold 59 NPs, further investigations should be focused on how each organ responds to the gold NPs, and how the 60 expression of genes in each tissues restore homeostasis. 62C. elegans is a transparent animal with multiple important signaling pathways conserved in mammals, 63 like autophagy, insulin, and apoptosis signaling pathways 24 . We analyzed the RNA sequencing data set 64 (GSE32521) from gold NPs exposed worm. However, different with the biodistribution data, the results 65 showed that the nerve system was the most affected when exposing organisms to gold NPs. Further 66 studies show that the oxidative stress transcription factor DAF-16 and HSF-1 are the main transcription 67 factors that regulate the gold NP-induced gene expressions. The ion-channel protein analysis indicated 68 that the potassium and solute carrier (SLC) channels are the most altered channels by gold NPs, which 69 could be the direct way of how gold NPs affect neuron activity. 70 5 71 Materials and Methods 72RNA sequencing data Analysis 73The RNA sequencing data, reference series GSE32521, was obtained from Gene Expression Omnibus, 74National Center for Biotechnology Information. Age-synchronized L3 worms were exposed to 4 nm gold 75NPs with a concentration of 5.9 mg/L in 50% K-Medium. Then they were cultured with 50% K-Medium 76 and left for another 12h. The RNA was extracted from each of the replicates. Significantly changed genes 77 with 1.5 fold and p < 0.05 and FDR < 0.1 were analyzed 23 . 79Gene Expression Analysis 80...

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Zinc-Oxide Nanoparticles Exhibit Genotoxic, Clastogenic, Cytotoxic and Actin Depolymerization Effects by Inducing Oxidative Stress Responses in Macrophages and Adult Mice

Cited by 119 publications

References 74 publications

Nanoparticle–Cell Interaction: A Cell Mechanics Perspective

Nanoparticle–Cell Interaction: A Cell Mechanics Perspective

Emerging metrology for high-throughput nanomaterial genotoxicology

The nervous system is the major target for Gold nanoparticles: Evidence from RNA sequencing data of C. elegans

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