New “omics” approaches as a tool to explore mechanistic nanotoxicology

Ventura, Célia; Vieira, Luís; Silva, Catarina; Silva, Maria João

http://hdl.handle.net/10400.18/7053

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Abstract(s)

In the last years, genomic approaches have been applied to study the toxicity of nanomaterials with the aim of obtaining insightful information on their effects on gene expression and consequent cellular changes. Toxicogenomics expects to find unique transcriptional profiles that, besides providing evidence of the mechanistic mode of action of nanomaterials, may also be used as biomarkers for biomonitoring purposes. Moreover, several nanomaterials have been associated with epigenetic alterations, i.e., changes in the regulation of gene expression caused by DNA methylation, histone tail alterations and differential microRNA (miRNA) expression. DNA methylation is frequently studied when analysing the epigenetic regulation of gene expression and the role of miRNAs is being increasingly understood, either promoting or supressing biological pathways. Consequently, the identification of the differently expressed miRNAs in cells or tissues after exposure to a toxic can allow the recognition of its possible mechanisms of action. An example of an epigenomic study will be presented, focusing on the exposure of epithelial alveolar cells to a multi-walled carbon nanotube (MWCNT) and asbestos (crocidolite). MWCNTs are one of the most promising products of nanotechnology with an extensive variety of applications in industry and biomedicine. Several toxicological studies have demonstrated that exposure to some MWCNTs can induce immunotoxic, cytotoxic and genotoxic effects, and nowadays they are considered as an occupational hazard. Particularly, those with a fiber-like shape similar to asbestos have raised concern about their carcinogenicity, and one (MWCNT-7) was classified in Group 2B (IARC) as a possibly human carcinogenic. By elucidating the molecular pathways that are involved in key events of nanomaterials toxicity, the new “omics” studies are expected contribute to exclude or reduce the handling of hazardous nanomaterials in the workplace and support the implementation of regulation to protect human health.