Autor(es):
Tavares, Ana 
; Louro, Henriqueta ; Vital, Nádia ; Antunes, Susana ; Lavinha, João ; Silva, Maria João
Data: 2013
Identificador Persistente: http://hdl.handle.net/10400.18/1738
Origem: Repositório Científico do Instituto Nacional de Saúde
Assunto(s): Genotoxicidade Ambiental; Nanomaterials; Titanium Dioxide; Micronucleus
Descrição
Human exposure to manufactured nanomaterials such as titanium dioxide (TiO2), often used in sunscreens and cosmetics, has increased worldwide. Their specific properties, such as size and high surface area/mass, render them attractive for many applications, but may also be associated to higher toxicity in biological systems and adverse effects in humans. In the context of EU Joint Action NANOGENOTOX (www.nanogenotox.com), the present work aimed to analyse the potential genotoxic effects of a well-characterized TiO2 nanomaterial, correlating in vitro and in vivo effects. TiO2 dispersions were prepared according to a standardized protocol and were used for exposure of human cells (in vitro) or mice (in vivo). The cytokinesis-block micronucleus assay (OECD guideline 487) was performed in human bronchial epithelial cells (BEAS-2B) and primary cultures of human lymphocytes. Additionally, Comet assay was conducted in BEAS-2B cells. In vivo testing was carried out on a mouse model after exposure of groups of mice intravenously. The mammalian erythrocyte micronucleus test in mouse blood (OECD guideline 474) and comet assay in mouse organs were performed. Concurrent positive chemical controls and a nanoparticle control (ZnO) were included.
While the results obtained in BEAS-2B cells showed no induction of micronucleated cells, a significant increase was observed in human lymphocytes at the dose of 125 μg/ml. Exposure of BEAS-2B to TiO2 caused an increase in DNA damage detected by comet assay (3-fold increase, p< 0.006) although no dose-response effect was seen. In mice, there was no genotoxicity in both assays.
In summary, using a standardized preparation of nanomaterials, results obtained were mostly negative after TiO2 exposure, in both in vitro and in vivo assays. However, somewhat different genotoxicity outcomes may reflect tissue-specific effects affecting, e.g., cellular uptake of the nanomaterial.
