Toxicogenomic Profiling of 28 Nanomaterials in Mouse Airways.

Area of Science:

• Nanomaterial toxicology
• Computational toxicology
• Immunopathology

Background:

• Toxicogenomics offers advanced hazard assessment by integrating molecular data and computational analysis.
• Understanding engineered nanomaterials' (ENM) biological impact is crucial for safety evaluations.

Purpose of the Study:

• To investigate transcriptomic and immunopathological changes in mouse lungs following airway exposure to diverse ENMs.
• To correlate molecular responses with observed inflammatory effects and identify key toxicological markers.

Main Methods:

• Mice were exposed via oropharyngeal aspiration to 28 ENMs with varied core compositions, surface chemistries, sizes, and shapes.
• Lung tissues underwent histological, cytological, and transcriptomic analyses to assess toxicity.
• Computational methods were used to map molecular events and identify shared gene expression patterns.

Main Results:

• Transcriptomic alterations strongly correlated with inflammatory cell infiltration in lung tissues.
• Surface modification significantly influenced toxicity: amination enhanced inflammatory response, while PEGylation mitigated it.
• ENM core chemistry also played a role in toxicological outcomes.

Conclusions:

• A shared set of 50 differentially expressed genes effectively clusters ENMs based on their toxicity.
• This comprehensive in vivo dataset is valuable for developing predictive models for ENM toxicity.
• Findings highlight the critical role of surface chemistry in modulating ENM-induced lung responses.