Journal
NANOTOXICOLOGY
Volume 10, Issue 7, Pages 913-923Publisher
TAYLOR & FRANCIS LTD
DOI: 10.3109/17435390.2016.1141338
Keywords
Genotoxicity; mechanistic toxicology; nanoparticles; TiO2; toxicity
Categories
Funding
- CEA through the Nanoscience and Toxicology research programs
- European Commission [NMP4-LA-2013-310451]
- Investissements d'Avenir French Government program of the French National Research Agency (ANR) through the A*MIDEX project [ANR-11-LABX-0064, ANR-11-IDEX-0001-02]
- QualityNano Project - European Community Research Infrastructures under the FP7 Capacities Program [INFRA-2010-262163]
- University of Birmingham
Ask authors/readers for more resources
Titanium dioxide nanoparticles (TiO2-NPs) are one of the most produced NPs in the world. Their toxicity has been studied for a decade using acute exposure scenarios, i.e. high exposure concentrations and short exposure times. In the present study, we evaluated their genotoxic impact using long-term and low concentration exposure conditions. A549 alveolar epithelial cells were continuously exposed to 1-50g/mL TiO2-NPs, 86% anatase/14% rutile, 24 +/- 6nm average primary diameter, for up to two months. Their cytotoxicity, oxidative potential and intracellular accumulation were evaluated using MTT assay and reactive oxygen species measurement, transmission electron microscopy observation, micro-particle-induced X-ray emission and inductively-coupled plasma mass spectroscopy. Genotoxic impact was assessed using alkaline and Fpg-modified comet assay, immunostaining of 53BP1 foci and the cytokinesis-blocked micronucleus assay. Finally, we evaluated the impact of a subsequent exposure of these cells to the alkylating agent methyl methanesulfonate. We demonstrate that long-term exposure to TiO2-NPs does not affect cell viability but causes DNA damage, particularly oxidative damage to DNA and increased 53BP1 foci counts, correlated with increased intracellular accumulation of NPs. In addition, exposure over 2 months causes cellular responses suggestive of adaptation, characterized by decreased proliferation rate and stabilization of TiO2-NP intracellular accumulation, as well as sensitization to MMS. Taken together, these data underline the genotoxic impact and sensitization effect of long-term exposure of lung alveolar epithelial cells to low levels of TiO2-NPs.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available