Titanium dioxide nanoparticles exhibit genotoxicity and impair DNA repair activity in A549 cells

Abstract

Titanium dioxide nanoparticles (TiO₂-NPs) are produced in large quantities, raising concerns about their impact for human health. The aim of this study was to deeply characterize TiO₂-NPs genotoxic potential to lung cells, and to link genotoxicity to physicochemical characteristics, e.g., size, specific surface area, crystalline phase. A549 cells were exposed to a panel of TiO₂-NPs with diameters ranging from 12 to 140 nm, either anatase or rutile. A set of complementary techniques (comet and micronucleus assays, gamma-H2AX immunostaining, 8-oxoGuanine analysis, H2-DCFDA, glutathione content, antioxidant enzymes activities) allowed us to demonstrate that small and spherical TiO₂-NPs, both anatase and rutile, induce single-strand breaks and oxidative lesions to DNA, together with a general oxidative stress. Additionally we show that these NPs impair cell ability to repair DNA, by inactivation of both NER and BER pathways. This study thus confirms the genotoxic potential of TiO₂-NPs, which may preclude their mutagenicity and carcinogenicity.

Keywords::

• Titanium dioxide
• nanoparticle
• genotoxicity
• oxidative stress
• DNA repair

Acknowledgement

The authors would like to thank D. Jaillard from CCME Orsay, France, for her help in transmission electron microscopy experiments, and S. Caillat from LAN, for his help in multiplexed DNA repair assays.

Declaration of interest: This study was funded by the French national research agency through the 2007-SEST-021 grant, by the ANSES through EST-0802 grant, and by CEA through internal Toxicology and Technology for health programs. The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.