Noves aproximacions per avaluar els efectes derivats de l'exposició a nanomaterials
- Autores: Sandra Ballesteros Ribera
- Directores de la Tesis: Ricardo Marcos Dauder (dir. tes.), Alba Hernández Bonilla (codir. tes.)
- Lectura: En la Universitat Autònoma de Barcelona ( España ) en 2021
- Idioma: catalán
- Tribunal Calificador de la Tesis: Noel Xamena López (presid.), Antonio Rodriguez Fernandez de Henestrosa (secret.), Adriana Sampayo Reyes (voc.)
- Programa de doctorado: Programa de Doctorado en Genética por la Universidad Autónoma de Barcelona
- Materias:
- Enlaces
- Tesis en acceso abierto en: TDX
- Resumen
Nanomaterials (NMs) are considered emerging pollutants that are increasingly detected in different environmental matrices, with potential risks for human health and the ecosystems. In this sense, the focus of this Thesis has been directed to provide new approach methodologies for hazard assessment of NMs via advanced in vitro and ex vivo models, as well as novel biomarkers.
From our first study, a novel approach was developed to understand the risk of polystyrene nanoparticles (PSNPs) exposure for humans, as a model of micro-nanoplastics (MNPLs). Thus, ex vivo whole blood samples from 5 donors were exposed to several doses of PSNPLs and different end-points were evaluated in diverse subsets of white peripheral blood cells (WBCs). The results showed sharp differences in PSNPLs internalization with very limited uptake in lymphocytes and high uptake in monocytes. Moreover, the genotoxic DNA damage evaluation revealed a specific cellular sensitivity, being polymorphonuclear cells (PMNs), and monocytes those cells with the most significant levels of genotoxic damage. Additionally, PSNPLs exposure triggered changes in the whole blood secretome, with a significant increase in the expression of cytokines related to the inflammatory, immune, and stress response, as well as cell proliferation.
In the second study, the before-mentioned whole blood ex vivo model was used to evaluate the impact of three different graphene-based nanomaterials (GBNMs) at the level of the blood secretome. For that purpose, a large panel of cytokines was analysed, and the results showed important cytokine expression changes, most of them related with the immune and inflammatory response. At the same time, the indirect soft-agar assay, was used to unravel the functional consequences of these cytokine changes. The results showed that the GBNMs-altered secretome can inhibit the anchorage-independent cell growth capacity of HeLa cells, used as a model cell-line.
In the third study, the cell-transforming properties of nanoceria were confirmed through a long-term low-dose in vitro model. Stem-like properties, anchorage-independent growth, and invasion abilities were analysed as they are considered important oncogenic features driven by NMs exposure. Also, their potential interactions with cigarette smoke condensate (CSC), as a model of environmental carcinogenic pollutant were confirmed, showing a positive interaction in the induction of cell transformation. Besides, a battery of microRNAs related to the acquisition of the tumoral phenotype was assessed, revealing that cerium dioxide nanoparticles (CeO2NPs) and the co-exposure produced potential toxicity at the transcriptome level.
Finally, our fourth study evaluated the potential epigenetic consequences of long-term exposure to titanium nanoparticles (TiO2NPs) and multi-walled carbon nanotubes (MWCNT), specifically the microRNAs expression changes. The analysed microRNA battery revealed a big impact on the expression profiling in cells exposed to both nanomaterials. Moreover, from our initial battery, a small set of five microRNAs were selected as potential biomarkers of effect after NMs’ exposures. This set was tested in BEAS-2B and MEF cells previously long-term exposed to different NMs, showing positive effects in all the tested samples, confirming the suitability of this battery.
