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Silica nanoparticles effects on gene expression of A549 cells

ABSTRACT: Expansion of nanotechnology will bring many potential benefits as adversely effects on human health. Protection of the human respiratory system from exposure of volatile nanoparticles has become an emerging health concern. The understanding of the biological processes involved in the development and maintenance of a variety of pathologies is improved by genome-wide approaches. Technical feasibility of this type of experiment has perfected in recent years, but data analysis remains challenging. In this context, gene set analysis has emerged as a fundamental tool for the interpretation of the results. We demonstrate how the use of a combination of gene-by-gene and gene set analyses can enhance the interpretation of results. Gene set analyses are able to distinguish responses due to nanoparticle size also discriminating between long and short time recovery after exposure. Transcription regulation and cell proliferation modulation appear to be an early response while oxidative stress and mitochondrial perturbation are late response. Moreover, smaller the particle higher the effect on inflammatory response and DNA damage activation. By integrating the two approaches, we evidenced the importance of MMP1, MMP9, MMP7 and MMP14 genes in response to Ludox® silica nanoparticles and the involvement apoptosis process in cell viability.

ORGANISM(S): Homo sapiens

PROVIDER: GSE53700 | GEO | 2014/09/08

SECONDARY ACCESSION(S): PRJNA232672

REPOSITORIES: GEO

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Project description:Despite the increased utilization of nanoparticles, the behavior and effect in the environment is largely unknown and few resources are available for health and environmental effect studies. Enchytraeids are extensively used in studies of soil ecotoxicology and recently, a cDNA microarray for Enchytraeus albidus was developed, allowing also toxicogenomic studies in this species. These organisms are ecologically relevant small worms that indirectly contribute to the regulation and degradation of organic matter. In this study we compared the gene expression profiles of E. albidus when exposed to copper-salt (CuCl2) and copper nanoparticles (Cu-NP) spiked soil. The worms were exposed for 48 hours in soil to a range of concentrations. Microarray hybridizations revealed different response patterns between copper-salt and copper nanoparticles exposed organisms, these differences are mainly related with transcripts involved in the energy metabolism of the organisms. Despite unknown gene function in the data-set there are indications that Cu-salt and Cu-NP exposure induced specific gene level responses. Fluorescently labelled cDNA, from enchytraeids exposed during 2 days to control soil (from Hygum site in Denmark) and to the different exposure conditions (Cy5), was synthesized for microarray analysis and hybridizations were performed. After scanning, spots were identified and ratios quantified using the QuantArray (Packard Biochip Technologies). Statistical analysis of the microarrays was performed using limmaGUI package (1.18.0) (Smyth, 2005) in the R (2.8.0) software environment (http://www.R-project.org/). After being submitted to local background subtraction, microarrays were normalized using global loess method. To statistically evaluate the differential gene expression between the different conditions, a gene-per-gene linear model (limma – linear model for microarray analysis) and empirical Bayes methods were applied. The results were then corrected for multiple testing using the Benjamini-Hochberg’s method (adjusted p<0.05 was considered significant) (Benjamini and Hochberg, 1995).

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Silica nanoparticles effects on gene expression of A549 cells

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