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Centre for Toxicogenomics and Human Health
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Cellular Mechanisms of Toxicity of Ingested Nanomaterials
Publication . Vieira, Adriana Isabel Ramos; Louro, Maria Henriqueta; Silva, Maria João
Titanium dioxide (TiO2) nanomaterials (NMs) are used in a variety of consumer products, namely in the food sector, but their application has raised some concerns regarding their negative impacts on human health and particularly, on the gastrointestinal tract (GIT) following digestion, as this may be a major route of exposure. However, the toxicity studies currently available in the literature are contradictory and the majority do not consider the influence of human digestion in the ingested NMs safety assessment.
This work aimed to understand the potential toxic effects of three TiO2 NMs (NM-102, NM-103 and NM-105) with distinct physicochemical properties, in the intestine, using human intestinal cells (Caco-2 and HT29-MTX-E12) as in vitro models. It was also intended to comprehend the impact of an in vitro simulated human digestion process on the NMs’ characteristics and to correlate these differences with the toxicity induced by digested TiO2 NMs, in comparison with undigested NMs.
Regarding the cytotoxicity, both undigested and digested NM-105 led to a decrease in HT29-MTX-E12 cell viability, which was more pronounced in the digested sample, concomitantly with a decrease in its hydrodynamic size. Furthermore, digested NM-105 induced an increase in the DNA strand break level in both cell lines and in oxidative DNA damage, only in HT29-MTX-E12 cells, thus being classified as potentially genotoxic, through the comet assay. Digested NM-103 showed also an equivocal genotoxic response in Caco-2 cells. FPG-modified comet assay revealed an induction of DNA oxidative base lesions in Caco-2 and HT29-MTX-E12 exposed to undigested NM-103 and NM-102. Lastly, through the micronucleus assay, increased chromosomal damage effects were observed following treatment with some of the undigested and digested NMs.
The present results reinforce the conception that NMs biological interactions are context-dependent, since their physicochemical properties can be changed after the digestion process, consequently leading to different biological effects.
Genotoxicity of Three Micro/Nanocelluloses with Different Physicochemical Characteristics in MG-63 and V79 Cells
Publication . Ventura, Célia; Marques, Catarina; Cadete, João; Vilar, Madalena; Pedrosa, Jorge F. S.; Pinto, Fátima; Fernandes, Susete Nogueira; Rosa, Rafaela Raupp da; Godinho, Maria Helena; Ferreira, Paulo J. T.; Louro, Henriqueta; Silva, Maria João; Centre for Toxicogenomics and Human Health (ToxOmics); DCM - Departamento de Ciência dos Materiais; CENIMAT-i3N - Centro de Investigação de Materiais (Lab. Associado I3N); MDPI - Multidisciplinary Digital Publishing Institute
Nanocellulose is an innovative engineered nanomaterial with an enormous potential for use in a wide array of industrial and biomedical applications and with fast growing economic value. The expanding production of nanocellulose is leading to an increased human exposure, raising concerns about their potential health effects. This study was aimed at assessing the potential toxic and genotoxic effects of different nanocelluloses in two mammalian cell lines; (2) Methods: Two micro/nanocelluloses, produced with a TEMPO oxidation pre-treatment (CNFs) and an enzymatic pre-treatment (CMFs), and cellulose nanocrystals (CNCs) were tested in osteoblastic-like human cells (MG-63) and Chinese hamster lung fibroblasts (V79) using the MTT and clonogenic assays to analyse cytotoxicity, and the micronucleus assay to test genotoxicity; (3) Results: cytotoxicity was observed by the clonogenic assay in V79 cells, particularly for CNCs, but not by the MTT assay; CNF induced micronuclei in both cell lines and nucleoplasmic bridges in MG-63 cells; CMF and CNC induced micronuclei and nucleoplasmic bridges in MG-63 cells, but not in V79 cells; (4) Conclusions: All nanocelluloses revealed cytotoxicity and genotoxicity, although at different concentrations, that may be related to their physicochemical differences and availability for cell uptake, and to differences in the DNA damage response of the cell model.
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Entidade financiadora
Fundação para a Ciência e a Tecnologia
Programa de financiamento
6817 - DCRRNI ID
Número da atribuição
UIDB/00009/2020