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

Abstract

Titanium dioxide nanoparticles (TiO(2)-NPs) are produced in large quantities, raising concerns about their impact for human health. The aim of this study was to deeply characterize TiO(2)-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 TiO(2)-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 TiO(2)-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 TiO(2)-NPs, which may preclude their mutagenicity and carcinogenicity.

Molecular responses of alveolar epithelial A549 cells to chronic exposure to titanium dioxide nanoparticles: A proteomic view

“…P53 is a central player in the DNA damage response. Its activation can be directly caused by the DNA damage that we and others previously reported in cells exposed to TiO 2 -NPs either acutely [4,21,48] or chronically [13] and which is characterized by oxidative lesions and DNA strand breaks, including double-strand breaks that may result from the duplication of cells with replication fork blockade [48]. It may also be linked to the impaired glucose metabolism that our proteomics results reveal; indeed p53 is also activated upon cell starvation and metabolic stress [49].…”

“…The energy delivered by our sonicator was measured, amplitude of 28% corresponds to 16.7 W [20]. The physico-chemical properties of these TiO 2 -NPs have already been described in our previous articles [19,21]. Briefly, their crystalline structure is mixed anatase/rutile (86%/14%) [21], their primary diameter is 25±7 nm and their specific surface area is 46±1 m²/g [19].…”

“…Cell viability was determined using the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) assay as described previously [21].…”

Genotoxicity, potential cytotoxicity and cell uptake of titanium dioxide nanoparticles in the marine fish Trachinotus carolinus (Linnaeus, 1766)

“…Titanium dioxide nanoparticles (TiO 2 -NP) are widely used in the manufacture of paints, paper, plastic, laminate flooring materials, food coloring and cosmetics (Jugan et al, 2012). Due to their photocatalytic properties these nanoparticles are also used in wastewater and as environmental disinfectants (Cho et al, 2004).…”

Toxicology of nanosized titanium dioxide: an update

“…They also observed that the DNA damage caused by nano-TiO 2 was single-strand breaks and 8-oxodGuo, but not double-strand breaks or chromosomal breaks or losses. Furthermore, the nanoparticles inactivated both nucleotide excision repair abilities (NER) and base excision repair (BER) pathways leading to the losing of cell ability to repair the damaged DNA (Jugan et al 2012). Two more recent papers presented similar conclusion.…”