Toxicogenomic Profiling of 28 Nanomaterials in Mouse Airways
Autor: | Richard D. Handy, Hannu Norppa, Pia Anneli Sofia Kinaret, Tiina Skoog, Marit Ilves, Henrik Wolff, Gerard Vales, Sergio Moya, Harri Alenius, Kai Savolainen, Piia Karisola, Juha Kere, Bengt Fadeel, Dario Greco, Joseph Ndika |
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Přispěvatelé: | Tampere University, BioMediTech, Institute of Biotechnology, Helsinki Institute of Life Science HiLIFE, University of Helsinki, HUMI - Human Microbiome Research, Research Programs Unit, Juha Kere / Principal Investigator, Staff Services |
Jazyk: | angličtina |
Rok vydání: | 2021 |
Předmět: |
Glycosylation
General Chemical Engineering Science General Physics and Astronomy Medicine (miscellaneous) 02 engineering and technology 010402 general chemistry 01 natural sciences Biochemistry Genetics and Molecular Biology (miscellaneous) Toxicogenetics Nanomaterials Transcriptome chemistry.chemical_compound transcriptomics Mice In vivo Animals General Materials Science Lung Research Articles nanomaterials 318 Medical biotechnology immunotoxicity Chemistry General Engineering 021001 nanoscience & nanotechnology airway exposure 3. Good health 0104 chemical sciences Cell biology Nanostructures Mice Inbred C57BL Nanotoxicology toxicogenomics Toxicity Models Animal PEGylation nanoparticles Female 3111 Biomedicine nanotoxicology 221 Nano-technology 0210 nano-technology Toxicogenomics Research Article |
Zdroj: | Advanced Science Advanced Science, Vol 8, Iss 10, Pp n/a-n/a (2021) |
ISSN: | 2198-3844 |
Popis: | 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. C57BL/6 mice are exposed by oropharyngeal aspiration to 28 different engineered nanomaterials (ENM). Histological and cytological evaluation together with transcriptomics analyses reveals the important effect of surface functionalization (amination, carboxylation, or pegylation) as well as the significant role of the ENM core chemistry. |
Databáze: | OpenAIRE |
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