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High-throughput, quantitative assessment of the effects of low-dose silica nanoparticles on lung cells: grasping complex toxicity with a great depth of field

Overview of attention for article published in BMC Genomics, April 2015
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Title
High-throughput, quantitative assessment of the effects of low-dose silica nanoparticles on lung cells: grasping complex toxicity with a great depth of field
Published in
BMC Genomics, April 2015
DOI 10.1186/s12864-015-1521-5
Pubmed ID
Authors

Cédric Pisani, Jean-Charles Gaillard, Virginie Nouvel, Michaël Odorico, Jean Armengaud, Odette Prat

Abstract

The toxicity of manufactured fumed silica nanoparticles (NPs) remains poorly investigated compared to that of crystalline silica NPs, which have been associated with lung diseases after inhalation. Amorphous silica NPs are a raw material for manufactured nanocomposites, such as cosmetics, foods, and drugs, raising concerns about their potential toxicity. The size of the NPs was determined by dynamic light scattering and their shape was visualized by atomic force microscopy (10 ± 4 nm). The pertinent toxicological concentration and dynamic ranges were determined using viability tests and cellular impedance. We combined transcriptomics and proteomics to assess the cellular and molecular effects of fumed silica in A549 human alveolar epithelial cells. The "no observed transcriptomic adverse effect level" (NOTEL) was set to 1.0 μg/cm(2), and the "lowest observed adverse transcriptional effect level" (LOTEL) was set at 1.5 μg/cm(2). We carried out genome-wide expression profiles with microarrays and identified, by shotgun proteomics, the exoproteome changes in lung cells after exposure to NP doses (0.1, 1.0, 1.5, 3.0, and 6.0 μg/cm(2)) at two time points (24 h and 72 h). The data revealed a hierarchical, dose-dependent cellular response to silica NPs. At 1.5 μg/cm(2), the Rho signaling cascade, actin cytoskeleton remodeling, and clathrin-mediated endocytosis were induced. At 3.0 μg/cm(2), many inflammatory mediators were upregulated and the coagulation system pathway was triggered. Lastly, at 6.0 μg/cm(2), oxidative stress was initiated. The proteins identified in the extracellular compartment were consistent with these findings. The alliance of two high-throughput technologies allowed the quantitative assessment of the cellular effects and molecular consequences of exposure of lung cells to low doses of NPs. These results were obtained using a pathway-driven analysis instead of isolated genes. As in photography, toxicogenomics allows, at the same time, the visualization of a wide spectrum of biological responses and a "zoom in" to the details with a great depth of field. This study illustrates how such an approach based on human cell culture models is a valuable predictive screening tool to evaluate the toxicity of many potentially harmful emerging substances, alone or in mixtures, in the framework of future regulatory reinforcements.

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Mendeley readers

The data shown below were compiled from readership statistics for 47 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
United States 1 2%
Unknown 46 98%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 11 23%
Researcher 11 23%
Student > Master 7 15%
Student > Doctoral Student 4 9%
Student > Bachelor 3 6%
Other 5 11%
Unknown 6 13%
Readers by discipline Count As %
Agricultural and Biological Sciences 11 23%
Pharmacology, Toxicology and Pharmaceutical Science 6 13%
Chemistry 5 11%
Nursing and Health Professions 3 6%
Engineering 3 6%
Other 8 17%
Unknown 11 23%

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 21 January 2016.
All research outputs
#7,173,117
of 8,295,152 outputs
Outputs from BMC Genomics
#5,180
of 5,857 outputs
Outputs of similar age
#277,953
of 331,912 outputs
Outputs of similar age from BMC Genomics
#264
of 283 outputs
Altmetric has tracked 8,295,152 research outputs across all sources so far. This one is in the 1st percentile – i.e., 1% of other outputs scored the same or lower than it.
So far Altmetric has tracked 5,857 research outputs from this source. They receive a mean Attention Score of 4.2. This one is in the 1st percentile – i.e., 1% of its peers scored the same or lower than it.
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We're also able to compare this research output to 283 others from the same source and published within six weeks on either side of this one. This one is in the 1st percentile – i.e., 1% of its contemporaries scored the same or lower than it.