Dataset Information

Toxicogenomic Profiling of 28 Nanomaterials in Mouse Airways.

ABSTRACT: Toxicogenomics opens novel opportunities for hazard assessment by utilizing computational methods to map molecular events and biological processes. In this study, the transcriptomic and immunopathological changes associated with airway exposure to a total of 28 engineered nanomaterials (ENM) are investigated. The ENM are selected to have different core (Ag, Au, TiO₂, CuO, nanodiamond, and multiwalled carbon nanotubes) and surface chemistries (COOH, NH₂, or polyethylene glycosylation (PEG)). Additionally, ENM with variations in either size (Au) or shape (TiO₂) are included. Mice are exposed to 10 µg of ENM by oropharyngeal aspiration for 4 consecutive days, followed by extensive histological/cytological analyses and transcriptomic characterization of lung tissue. The results demonstrate that transcriptomic alterations are correlated with the inflammatory cell infiltrate in the lungs. Surface modification has varying effects on the airways with amination rendering the strongest inflammatory response, while PEGylation suppresses toxicity. However, toxicological responses are also dependent on ENM core chemistry. In addition to ENM-specific transcriptional changes, a subset of 50 shared differentially expressed genes is also highlighted that cluster these ENM according to their toxicity. This study provides the largest in vivo data set currently available and as such provides valuable information to be utilized in developing predictive models for ENM toxicity.

SUBMITTER: Kinaret PAS

PROVIDER: S-EPMC8132046 | biostudies-literature | 2021 May

REPOSITORIES: biostudies-literature

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Toxicogenomic Profiling of 28 Nanomaterials in Mouse Airways.

Kinaret Pia A S PAS Ndika Joseph J Ilves Marit M Wolff Henrik H Vales Gerard G Norppa Hannu H Savolainen Kai K Skoog Tiina T Kere Juha J Moya Sergio S Handy Richard D RD Karisola Piia P Fadeel Bengt B Greco Dario D Alenius Harri H

Advanced science (Weinheim, Baden-Wurttemberg, Germany) 20210308 10

Toxicogenomics opens novel opportunities for hazard assessment by utilizing computational methods to map molecular events and biological processes. In this study, the transcriptomic and immunopathological changes associated with airway exposure to a total of 28 engineered nanomaterials (ENM) are investigated. The ENM are selected to have different core (Ag, Au, TiO<sub>2</sub>, CuO, nanodiamond, and multiwalled carbon nanotubes) and surface chemistries (COOH, NH<sub>2</sub>, or polyethylene glyc ...[more]

PMID: 34026454

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Project description:Common inbred mouse strains, such as the C57BL/6 (C57) and the SWV, display differences in sensitivity to environmental teratogens during gestation. For example, the C57 is more sensitive than the SWV to cadmium (Cd) exposure during neurulation, inducing a higher incidence of neural tube defects (NTDs). Here, we report, using Cd as a model teratogen, the first large scale toxicogenomic study to compare teratogen-induced gene expression alterations in C57 and SWV embryos undergoing neurulation, identifying toxicogenomic responses that associate with developmental toxicity and differential sensitivity. Using a systems-based toxicogenomic approach, comparing Cd-exposed and control C57 and SWV embryos (12- and 24-h postinjection [p.i.] [gestational day 8.0, ip]), we examined differentially expressed genes at multiple levels (biological process, pathway, gene) using Gene Ontology (GO) analysis, pathway mapping and cross-scatter plots. In both C57 and SWV embryos, we observed several gene expression alterations linked with cell cycle-related classifications, however, only in the C57 we observed upregulation of p53-dependent mediators Ccng1 and Pmaip1, previously associated with cell cycle arrest, apoptosis and NTD formation. In addition, we also identified a greater reduction in expression of nervous system development-related genes (e.g., Zic1, En2, Neurog1, Elavl4, Metrn, Nr2f1, Nr2f2) in the C57 compared to the SWV (12-h p.i.). In summary, our results indicate that differences in Cd-induced gene expression profiles between NTD resistant and sensitive strains within enriched biological processes (including developmental and cell cycle-related categories) associate with increased sensitivity to developmental toxicity as determined by observations of increased NTD formation, mortality (resorptions) and reduced fetal growth. Such observations may provide more detailed and useful mechanistic clues for identification of differences in life-stage specific teratogenic response.

Dataset Information

Toxicogenomic Profiling of 28 Nanomaterials in Mouse Airways.

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Toxicogenomic Profiling of 28 Nanomaterials in Mouse Airways.

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