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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Nov 03, 2022 |
| Title |
Impact of copper oxide particle dissolution on lung epithelial cell toxicity: response characterization using global transcriptional analysis |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
The in vitro and in vivo toxicity of copper oxide nanoparticles (CuO NPs) is attributed to both particle and dissolved copper ion species. However, a clear understanding of 1) the specific cellular responses that are modulated by the two species and 2) the temporal dynamics in toxicity, as the proportional amount of particulate and ionic forms change over time, is lacking.
In the current study, in vitro responses to microparticulate CuO (CuO MPs), CuO NPs, and dissolved Cu2+ were characterized in order to elucidate particle and ion induced kinetic effects. Particle dissolution experiments were carried out in relevant cell culture medium, using CuO NPs and MPs. Mouse lung epithelial cells were exposed for 2 - 48 h with 1 - 25 µg/mL CuO MPs, CuO NPs, or 7 & 54 µg/mL CuCl2. Cellular viability and genome-wide transcriptional responses were assessed.
Dose and time dependent cytotoxicity was observed in CuO NP exposed cells, which was delayed and subtle in CuCl2 and not observed in CuO MPs treated cells. Analyses of differentially expressed genes and associated pathway perturbations showed that dissolved ions released by CuO NPs in extracellular medium are insufficient to account for the observed potency and cytotoxicity. Further organization of gene expression results in an Adverse Outcome Pathway (AOP) framework revealed a series of key events potentially involved in CuO NPs toxicity. The AOP is applicable to soluble metal oxide nanoparticle induced toxicity in general, and thus, can facilitate the development of in vitro alternative strategies to screen their toxicity.
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| Overall design |
Purified and extracted RNA from pelleted immortalized mouse lung epithelial cells (FE1) exposed to 0, 1, 5, 10, or 25 ug/mL copper oxide nanoparticles (CuO NPs) or microparticles (CuO MPs), or 0, 7 ug/mL CuCl2, or 5 ug/mL NaCl for 2, 24, or 48 hours
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| Contributor(s) |
Boyadzhiev A, Williams A, Halappanavar S |
| Citation(s) |
33507836, 38203705 |
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| Submission date |
Nov 06, 2020 |
| Last update date |
Jan 18, 2024 |
| Contact name |
Sabina Halappanavar |
| E-mail(s) |
sabina.halappanavar@hc-sc.gc.ca
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| Organization name |
Health Canada
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| Street address |
251 Sir Frederick Banting Driveway
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| City |
Ottawa |
| State/province |
ON |
| ZIP/Postal code |
K1A 0K9 |
| Country |
Canada |
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| Platforms (1) |
| GPL21163 |
Agilent-074809 SurePrint G3 Mouse GE v2 8x60K Microarray [Probe Name version] |
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| Samples (107)
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| Relations |
| BioProject |
PRJNA675114 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE161017_RAW.tar |
646.2 Mb |
(http)(custom) |
TAR (of TXT) |
| Processed data included within Sample table |
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