Genotoxicity evaluation of amorphous silica nanoparticles of different sizes using the micronucleus and the plasmid<i>lacZ</i>gene mutation assay

Park, Margriet V. D. Z.; Verharen, Henny W.; Zwart, Edwin; Hernández, Lya G.; Benthem, Jan van; Elsaesser, Andreas; Barnes, Clifford A.; McKerr, George; Howard, C. Vyvyan; Salvati, Anna; Lynch, Iseult; Dawson, Kenneth A.; Jong, Wim H. de

doi:10.3109/17435390.2010.506016

Cited by 80 publications

(44 citation statements)

References 47 publications

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“…There is paucity data regarding genotoxicity for SiO 2 nanoparticles. Park MV et al used the micronucleus (MN) assay to report that 80 nm SiO 2 nanoparticles caused chromosome distortions in 3T3-L1 mouse inoblasts, and that the SiO 2 nanoparticles of size at 30 and 80 nm elicited mutagenesis of embryonal inoblasts carried the lacZ reporter gene by mouse (Park et al, 2011b). In HT29, HaCat, and A549 cells, DNA injury determined using the comet assay was evidently observed at SiO 2 nanoparticle (14 nm diameter) dosages of 0.1-10 mg/mL (Mu et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

Cytotoxicity and DNA damage in mouse macrophages exposed to silica nanoparticles

Yang¹,

Wu²,

Lao³

et al. 2016

Genet. Mol. Res.

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ABSTRACT. Silica (SiO 2 ) nanoparticles are being progressively applied in various applications, including cosmetics, food technology, and medical diagnostics. Although crystalline SiO 2 is a known carcinogen, the carcinogenicity of SiO 2 nanoparticles remains unclear. Here, we assessed the cytotoxic effects and DNA injury induced by exposure to various dosages of SiO 2 nanoparticles at 0-2400 mg/mL (0-3200 mg/mL microscale SiO 2 as positive control) for 24 h using RAW264.7 cells, followed by methyl tetrazolium (MTT) assay. Cells were also treated by 31.25, 125, and 500 mg/mL SiO 2 nanoparticles (500 mg/mL microscale SiO 2 as positive control) for 24 h and examined by single cell gel electrophoresis assay (SCEG) and flow cytometry. Outstanding dose-related decline in cell viability was observed with enhancing dosages of SiO 2 nanoparticles by MTT assay. The inhibitory concentration 50% of SiO 2 nanoparticles and microscale SiO 2 was 16690 and 5080 mg/mL, respectively. The comet rate (comet%), length of tail, the percentage in DNA tail (TDNA%) and olive tail moment (OTM) induced by SiO 2 nanoparticles were significantly increased in comparison with control and microscale SiO 2 at 500 mg/mL. 500 mg/mL SiO 2 nanoparticles and microscale SiO 2 caused a significant increase in apoptosis rate, decreased proliferation index and increased cell proportions in G 0 /G 1 phases by contrast to the negative control (P < 0.05). This indicates that SiO 2 nanoparticles are more cytotoxic than microscale SiO 2 particles; they induce DNA injury, increase apoptosis, and decrease the proliferation index in RAW264.7 cells. DNA injury and apoptosis may be involved in reducing cell proliferation.

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Section: Introductionmentioning

confidence: 99%

Cytotoxicity and DNA damage in mouse macrophages exposed to silica nanoparticles

Yang¹,

Wu²,

Lao³

et al. 2016

Genet. Mol. Res.

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“…4 However, genotoxicity induced by amorphous silica nanoparticles seems to be cell-line dependent. [5][6][7] Overall, little is known about the toxicological effects of nanoparticles on the vasculature.…”

Section: Introductionmentioning

confidence: 99%

Amorphous silica nanoparticles trigger nitric oxide/peroxynitrite imbalance in human endothelial cells: inflammatory and cytotoxic effects

Medina¹,

Jacoby²,

Malinski³

et al. 2011

IJN

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Background The purpose of this study was to investigate the mechanism of noxious effects of amorphous silica nanoparticles on human endothelial cells. Methods Nanoparticle uptake was examined by transmission electron microscopy. Electrochemical nanosensors were used to measure the nitric oxide (NO) and peroxynitrite (ONOO − ) released by a single cell upon nanoparticle stimulation. The downstream inflammatory effects were measured by an enzyme-linked immunosorbent assay, real-time quantitative polymerase chain reaction, and flow cytometry, and cytotoxicity was measured by lactate dehydrogenase assay. Results We found that the silica nanoparticles penetrated the plasma membrane and rapidly stimulated release of cytoprotective NO and, to a greater extent, production of cytotoxic ONOO − . The low [NO]/[ONOO − ] ratio indicated increased nitroxidative/oxidative stress and correlated closely with endothelial inflammation and necrosis. This imbalance was associated with nuclear factor κB activation, upregulation of key inflammatory factors, and cell death. These effects were observed in a nanoparticle size-dependent and concentration-dependent manner. Conclusion The [NO]/[ONOO − ] imbalance induced by amorphous silica nanoparticles indicates a potentially deleterious effect of silica nanoparticles on vascular endothelium.

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“…Regarding the genotoxicity induced by SiO 2 nanoparticles, several publications have reported on in vitro micronucleus tests. 11,15,47,51,52 In contrast, few in vivo micronucleus tests have been performed. Downs et al conducted in vivo micronucleus testing of SiO 2 nanoparticles, where they analyzed micronuclei in rat blood.…”

Section: Discussionmentioning

confidence: 99%

Undetactable levels of genotoxicity of SiO2 nanoparticles in in vitro and in vivo tests

Kwon

Kim

Lee

et al. 2014

IJN

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Background Silica dioxide (SiO 2 ) has been used in various industrial products, including paints and coatings, plastics, synthetic rubbers, and adhesives. Several studies have investigated the genotoxic effects of SiO 2 ; however, the results remain controversial due to variations in the evaluation methods applied in determining its physicochemical properties. Thus, well characterized chemicals and standardized methods are needed for better assessment of the genotoxicity of nanoparticles. Methods The genotoxicity of SiO 2 was evaluated using two types of well characterized SiO 2 , ie, 20 nm (−) charge (SiO EN20(−) 2) and 100 nm (−) charge (SiO EN100(−) 2). Four end point genotoxicity tests, ie, the bacterial mutation assay, in vitro chromosomal aberration test, in vivo comet assay, and in vivo micronucleus test, were conducted following the test guidelines of the Organization for Economic Cooperation and Development (OECD) with application of Good Laboratory Practice. Results No statistically significant differences were found in the bacterial mutation assay, in vitro chromosomal aberration test, in vivo comet assay, and in vivo micronucleus test when tested for induction of genotoxicity in both two types of SiO 2 nanoparticles. Conclusion These results suggest that SiO 2 nanoparticles, in particular SiO 2 EN20(−) and SiO 2 EN100(−) , are not genotoxic in both in vitro and in vivo systems under OECD guidelines. Further, the results were generated in accordance with OECD test guidelines, and Good Laboratory Practice application; it can be accepted as reliable information regarding SiO 2 -induced genotoxicity.

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Genotoxicity evaluation of amorphous silica nanoparticles of different sizes using the micronucleus and the plasmidlacZgene mutation assay

Cited by 80 publications

References 47 publications

Cytotoxicity and DNA damage in mouse macrophages exposed to silica nanoparticles

Cytotoxicity and DNA damage in mouse macrophages exposed to silica nanoparticles

Amorphous silica nanoparticles trigger nitric oxide/peroxynitrite imbalance in human endothelial cells: inflammatory and cytotoxic effects

Undetactable levels of genotoxicity of SiO2 nanoparticles in in vitro and in vivo tests

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