Assessment of the cellular effects of ingested titanium dioxide nanomaterials in intestinal cells

• Main Author: Gramacho, Ana Catarina Rodrigues
• Publication Date: 2019
• Format: Master thesis
• Language: eng
• Source: Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)
• Download full: http://hdl.handle.net/10362/87919
• topic: Nanomaterials; Titanium dioxide; Simulated digestion; Cytotoxicity; Genotoxicity; Domínio/Área Científica::Engenharia e Tecnologia::Engenharia Química

The wide commercialization of consumer products containing titanium dioxide nanomaterials (TiO2 NMs) contributes to a substantial increase of human exposure to this compound, which is worrying for public health, since the existent studies generated contradictory results about TiO2 safety. The oral exposure may occur either directly, through the consumption of products/pharmaceuticals containing NMs, or indirectly, through the ingestion of contaminated food. Therefore, the gastrointestinal tract appears to be a probable route of exposure to NMs. The fact that physicochemical properties of the NMs are dependent of the context can contribute to explain the different outcomes. This work aimed to investigate the bio-nano interactions of three TiO2 NMs (from Joint Research Centre, Ispra) with different physicochemical properties in the context of intestinal tract and digestion processes, to better understand key events that may be linked to adverse outcomes (AO). An in vitro digestion process was used to mimic human digestion and the resulting product was used for toxicity assessment in a human intestinal cell line (Caco-2), in comparison to undigested NMs. The cytotoxic and genotoxic effects of digested NMs were determined after the in vitro exposure of human intestinal cells (Caco-2). In addition, cellular uptake was investigated using confocal microscopy. The results indicated that undigested or digested NMs were not cytotoxic to cells in the studied conditions. Furthermore, none of the tested NMs, either directly or after digestion process, revealed genotoxic effects by the comet assay in intestinal cells exposed in vitro. In addition, no induction of micronucleus was detected, indicating that these TiO2 NMs do not induce clastogenic or aneugenic effects under the present conditions. However, the confocal microscopy images suggest that agglomerates of NM-102 and NM-103 can be internalized by Caco-2 cells, even reaching the nucleus, in case of NM-102, thus other genotoxic effects such as mutation induction or epigenetic effects may occur.