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Series GSE60797 Query DataSets for GSE60797
Status Public on Aug 20, 2015
Title Transcriptional profiling to identify physical-chemical properties detrimental to nanomaterial-induced pulmonary response (part 1)
Organism Mus musculus
Experiment type Expression profiling by array
Summary We examined the use of toxicogenomics data to 1) elucidate the underlying mechanisms of pulmonary responses following exposures to titanium dioxide (TiO2) nanoparticles (NPs) of different size and surface charge, and 2) determine if such responses are influenced by embedding particles in complex paint matrix. Adult C57BL/6 mice were exposed via single intratracheal instillation to three doses of free forms of NRCWE-030 (10.5 nm), NRCWE-025 (38 nm), NRCWE-001 (10 nm, neutral charge) NRCWE-002 (10 nm, positive charge) or to sanding dusts of paint consisting of NRCWE-030+NRCWE-025 or NRCWE-025 alone. Controls were exposed to dispersion medium without NPs. TiO2NPs were characterized for size, surface area, and agglomeration status in the exposure medium. Hyperspectral microscopy was performed to detect TiO2NPs in lungs and to determine the in vivo status of matrix-embedded TiO2NPs. Pulmonary gene expression profiles were generated using DNA microarrays on lung tissues collected at 24 h and 28 d post exposure time points. Bioinformatics tools were used to characterize size and surface property-pertinent effects. The data from 360 individual arrays were collapsed into 567 differentially expressed genes (False discovery rate adjusted P ≤ 0.05 and fold change ≥ 1.5 in any one condition). Unsupervised hierarchical clustering of the 567 genes revealed that TiO2NPs clustered mainly based on the post-exposure time points and then by the particle types. A meta analysis using pathway tools showed that the combination of smaller size and positive surface charge contributes to the potency of TiO2NPs. Although embedding in matrix dampens the overall toxicity of TiO2NPs, the smaller size positively influences the toxicity. Paint matrix itself did not induce any response. Finally, the observed differences in response reflected the differences in severity of the response and not the underlying mechanisms. Thus, transcriptional profiling is an effective tool to determine the important properties responsible for eliciting a response.
 
Overall design Female C57BL/6 mice of 5-7 weeks old were obtained from Taconic (Ry, Denmark) and were allowed to acclimatise for 1-3 weeks before the exposure. All mice were given food (Altromin no.1324, Christian Petersen, Denmark) and water ad libitum. Mice were grouped in polypropylene cages with sawdust bedding at controlled temperature 21±1°C, humidity 50 ±10 % in a 12 h-light: dark cycle. The experiments were approved by the Danish “Animal Experiments Inspectorate” and carried out following their guidelines for ethical conduct and care when using animals in research. Animals were exposed to 18, 54, or 162 ug of Indoor-NanoTiO2 and Indoor-R dispersed in 10% bronchoalveolar lavage fluid (BAL), 0.9% NaCl. Each exposure group consisted of minimum of 5 animals. Controls were exposed to vehicle only. The data were compared to their respective controls within the group.
 
Contributor(s) Williams A
Citation(s) 26885455
Submission date Aug 26, 2014
Last update date Jul 03, 2019
Contact name Andrew Williams
Organization name Health Canada
Street address 50 Colombine Dr
City Ottawa
State/province ON
ZIP/Postal code K1A0K9
Country Canada
 
Platforms (1)
GPL7202 Agilent-014868 Whole Mouse Genome Microarray 4x44K G4122F (Probe Name version)
Samples (70)
GSM1488780 Control 1d-C3
GSM1488781 Indoor-NanoTiO2 1d-L2
GSM1488782 Indoor-NanoTiO2 1d-H4
This SubSeries is part of SuperSeries:
GSE60801 Transcriptional profiling to identify physical-chemical properties detrimental to nanomaterial-induced pulmonary response
Relations
BioProject PRJNA259558

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE60797_RAW.tar 300.0 Mb (http)(custom) TAR (of TXT)
Processed data included within Sample table

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