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Research Project
A novelty study on the human uptake, genotoxicity and immunotoxicity of nanoparticles and legacy contaminants mixtures
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Publications
Assessing the in vitro toxicity of airborne (nano)particles to the human respiratory system: from basic to advanced models
Publication . Bessa, Maria João; Brandão, Fátima; Rosário, Fernanda; Moreira, Luciana; Reis, Ana Teresa; Valdiglesias, Vanessa; Laffon, Blanca; Fraga, Sónia; Teixeira, João Paulo
Several studies have been conducted to address the potential adverse health risks attributed to exposure to nanoscale materials. While in vivo studies are fundamental for identifying the relation-ship between dose and occurrence of adverse effects, in vitro model systems provide important information regarding the mechanism(s) of action at the molecular level. With a special focus on exposure to inhaled (nano)particulate material toxicity assessment, this review provides an over-view of the available human respiratory models and exposure systems for in vitro testing, advan-tages, limitations, and existing investigations using models of different complexity. A brief overview of the human respiratory system, pathway and fate of inhaled (nano)particles is also presented.
Salivary Leucocytes as In Vitro Model to Evaluate Nanoparticle-Induced DNA Damage
Publication . Valdiglesias, Vanessa; Fernández-Bertólez, Natalia; Lema-Arranz, Carlota; Rodríguez-Fernández, Raquel; Pásaro, Eduardo; Reis, Ana Teresa; Teixeira, João Paulo; Costa, Carla; Laffon, Blanca
Metal oxide nanoparticles (NPs) have a wide variety of applications in many consumer products and biomedical practices. As a result, human exposure to these nanomaterials is highly frequent, becoming an issue of concern to public health. Recently, human salivary leucocytes have been proposed as an adequate non-invasive alternative to peripheral blood leucocytes to evaluate genotoxicity in vitro. The present study focused on proving the suitability of salivary leucocytes as a biomatrix in the comet assay for in vitro nanogenotoxicity studies, by testing some of the metal oxide NPs most frequently present in consumer products, namely, titanium dioxide (TiO2), zinc oxide (ZnO), and cerium dioxide (CeO2) NPs. Primary and oxidative DNA damage were evaluated by alkaline and hOGG1-modified comet assay, respectively. Any possible interference of the NPs with the methodological procedure or the hOGG1 activity was addressed before performing genotoxicity evaluation. Results obtained showed an increase of both primary and oxidative damage after NPs treatments. These data support the use of salivary leucocytes as a proper and sensitive biological sample for in vitro nanogenotoxicity studies, and contribute to increase the knowledge on the impact of metal oxide NPs on human health, reinforcing the need for a specific regulation of the nanomaterials use.
Co-exposure with CeO2NPs results in an antagonistic effect on the cytotoxicity and genotoxicity of TiO2NP on A549 cells
Publication . Rosário, Fernanda; Vilaça, Cláudia; Costa, Carla; Lopes, Cláudia B.; Estrada, Ana C.; Tavares, Daniela S.; Teixeira, João Paulo; Reis, Ana Teresa
Objective: Assess the CYTOTOXIC and GENOTOXIC POTENTIAL resulting
from titanium dioxide nanoparticles (TiO2NP) and cerium oxide
nanoparticles (CeO2NP) co-exposure in human lung epithelial cell line
A549.
In Vitro Hepatotoxic and Neurotoxic Effects of Titanium and Cerium Dioxide Nanoparticles, Arsenic and Mercury Co-Exposure
Publication . Rosário, Fernanda; Costa, Carla; Lopes, Cláudia B.; Estrada, Ana C.; Tavares, Daniela S.; Pereira, Eduarda; Teixeira, João Paulo; Reis, Ana Teresa
Considering the increasing emergence of new contaminants, such as nanomaterials, mixing with legacy contaminants, including metal(loid)s, it becomes imperative to understand the toxic profile resulting from these interactions. This work aimed at assessing and comparing the individual and combined hepatotoxic and neurotoxic potential of titanium dioxide nanoparticles (TiO2NPs 0.75-75 mg/L), cerium oxide nanoparticles (CeO2NPs 0.075-10 μg/L), arsenic (As 0.01-2.5 mg/L), and mercury (Hg 0.5-100 mg/L) on human hepatoma (HepG2) and neuroblastoma (SH-SY5Y) cells. Viability was assessed through WST-1 (24 h) and clonogenic (7 days) assays and it was affected in a dose-, time- and cell-dependent manner. Higher concentrations caused greater toxicity, while prolonged exposure caused inhibition of cell proliferation, even at low concentrations, for both cell lines. Cell cycle progression, explored by flow cytometry 24 h post-exposure, revealed that TiO2NPs, As and Hg but not CeO2NPs, changed the profiles of SH-SY5Y and HepG2 cells in a dose-dependent manner, and that the cell cycle was, overall, more affected by exposure to mixtures. Exposure to binary mixtures revealed either potentiation or antagonistic effects depending on the composition, cell type and time of exposure. These findings prove that joint toxicity of contaminants cannot be disregarded and must be further explored.
Integrated Use of Bioaccumulation, Genotoxic, and Haematological Endpoints to Assess the Effect of Water Remediation Strategies on Fish Health: A Complementary Study
Publication . Mieiro, Cláudia; Coelho, João; Reis, Ana Teresa; Castro, Diana; Figueira, Paula; Martinho, Filipe; Pardal, Miguel; Pereira, Eduarda; Pacheco, Mário; Lopes, Cláudia
Biosorption successfully remediates saline water contaminated with legacy contaminants, but its effects on the health of marine organisms remain unclear. Therefore, our aim was to address this knowledge gap with data on the accumulation ability, as well as the cytogenetic and biochemical effects in turbot (Scophthalmus maximus). To this end, we exposed turbot for seven days to a mixture of remediated metals (Rem treatments: Cd, Hg, and Pb), with and without the presence of nanoparticles (NP), and compared them with the maximum allowable concentrations (MAC treatment) for effluent discharges. We determined the metal accumulation in the blood and kidney and evaluated haematological changes (red blood cell count, haemoglobin, and mean cell haemoglobin (MCH)) and genotoxicity (erythrocytic nuclear abnormalities assay) in the blood. The results showed that remediation with non-living macroalgae significantly reduced the metallic blood and kidney burdens in the Rem treatments. Furthermore, no genotoxic potential occurred in the Rem and MAC treatments in parallel with the reduction in MCH levels in the Rem treatments, which would reflect hematopoietic disturbances in the MAC. Our results validate biosorption remediation as we achieved a considerable reduction in metal loads while maintaining the health status of fish, highlighting the importance of testing water remediation methods in the biota.
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Funding agency
Fundação para a Ciência e a Tecnologia
Funding programme
Funding Award Number
SFRH/BPD/122112/2016