Investigating the Molecular Processes behind the Cell-Specific Toxicity Response to Titanium Dioxide Nanobelts

• Main Authors: Laurent A. Winckers, Chris T. Evelo, Egon L. Willighagen, Martina Kutmon
• Format: Article
• Language: English
• Published: MDPI AG 2021-08-01
• Series: International Journal of Molecular Sciences
• Subjects: nanomaterials; titanium dioxide; nanobelts; overrepresentation analysis; Gene Ontology; THP1
• Online Access: https://www.mdpi.com/1422-0067/22/17/9432

Some engineered nanomaterials incite toxicological effects, but the underlying molecular processes are understudied. The varied physicochemical properties cause different initial molecular interactions, complicating toxicological predictions. Gene expression data allow us to study the responses of genes and biological processes. Overrepresentation analysis identifies enriched biological processes using the experimental data but prompts broad results instead of detailed toxicological processes. We demonstrate a targeted filtering approach to compare public gene expression data for low and high exposure on three cell lines to titanium dioxide nanobelts. Our workflow finds cell and concentration-specific changes in affected pathways linked to four Gene Ontology terms (apoptosis, inflammation, DNA damage, and oxidative stress) to select pathways with a clear toxicity focus. We saw more differentially expressed genes at higher exposure, but our analysis identifies clear differences between the cell lines in affected processes. Colorectal adenocarcinoma cells showed resilience to both concentrations. Small airway epithelial cells displayed a cytotoxic response to the high concentration, but not as strongly as monocytic-like cells. The pathway-gene networks highlighted the gene overlap between altered toxicity-related pathways. The automated workflow is flexible and can focus on other biological processes by selecting other GO terms.