Titanium dioxide nanoparticles exhibit genotoxicity and impair DNA repair activity in A549 cells. 2012

Mary-Line Jugan, and Sabrina Barillet, and Angelique Simon-Deckers, and Nathalie Herlin-Boime, and Sylvie Sauvaigo, and Thierry Douki, and Marie Carriere
UMR3299 CEA-CNRS, Service Interdisciplinaire des Systèmes Moléculaires et Matériaux, Laboratoire Structure et Dynamique par Résonance Magnétique, CEA Saclay, Gif sur Yvette.

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.

UI MeSH Term Description Entries
D002460 Cell Line Established cell cultures that have the potential to propagate indefinitely. Cell Lines,Line, Cell,Lines, Cell
D002470 Cell Survival The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability. Cell Viability,Cell Viabilities,Survival, Cell,Viabilities, Cell,Viability, Cell
D004249 DNA Damage Injuries to DNA that introduce deviations from its normal, intact structure and which may, if left unrepaired, result in a MUTATION or a block of DNA REPLICATION. These deviations may be caused by physical or chemical agents and occur by natural or unnatural, introduced circumstances. They include the introduction of illegitimate bases during replication or by deamination or other modification of bases; the loss of a base from the DNA backbone leaving an abasic site; single-strand breaks; double strand breaks; and intrastrand (PYRIMIDINE DIMERS) or interstrand crosslinking. Damage can often be repaired (DNA REPAIR). If the damage is extensive, it can induce APOPTOSIS. DNA Injury,DNA Lesion,DNA Lesions,Genotoxic Stress,Stress, Genotoxic,Injury, DNA,DNA Injuries
D004260 DNA Repair The removal of DNA LESIONS and/or restoration of intact DNA strands without BASE PAIR MISMATCHES, intrastrand or interstrand crosslinks, or discontinuities in the DNA sugar-phosphate backbones. DNA Damage Response
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000704 Analysis of Variance A statistical technique that isolates and assesses the contributions of categorical independent variables to variation in the mean of a continuous dependent variable. ANOVA,Analysis, Variance,Variance Analysis,Analyses, Variance,Variance Analyses
D014025 Titanium A dark-gray, metallic element of widespread distribution but occurring in small amounts with atomic number, 22, atomic weight, 47.867 and symbol, Ti; specific gravity, 4.5; used for fixation of fractures.
D015162 Micronucleus Tests Induction and quantitative measurement of chromosomal damage leading to the formation of micronuclei (MICRONUCLEI, CHROMOSOME-DEFECTIVE) in cells which have been exposed to genotoxic agents or IONIZING RADIATION. Micronucleus Assays,Assay, Micronucleus,Assays, Micronucleus,Micronucleus Assay,Micronucleus Test,Test, Micronucleus,Tests, Micronucleus
D053758 Nanoparticles Nanometer-sized particles that are nanoscale in three dimensions. They include nanocrystaline materials; NANOCAPSULES; METAL NANOPARTICLES; DENDRIMERS, and QUANTUM DOTS. The uses of nanoparticles include DRUG DELIVERY SYSTEMS and cancer targeting and imaging. Nanocrystalline Materials,Nanocrystals,Material, Nanocrystalline,Materials, Nanocrystalline,Nanocrystal,Nanocrystalline Material,Nanoparticle
D018384 Oxidative Stress A disturbance in the prooxidant-antioxidant balance in favor of the former, leading to potential damage. Indicators of oxidative stress include damaged DNA bases, protein oxidation products, and lipid peroxidation products (Sies, Oxidative Stress, 1991, pxv-xvi). Anti-oxidative Stress,Antioxidative Stress,DNA Oxidative Damage,Nitro-Oxidative Stress,Oxidative Cleavage,Oxidative DNA Damage,Oxidative Damage,Oxidative Injury,Oxidative Nitrative Stress,Oxidative Stress Injury,Oxidative and Nitrosative Stress,Stress, Oxidative,Anti oxidative Stress,Anti-oxidative Stresses,Antioxidative Stresses,Cleavage, Oxidative,DNA Damage, Oxidative,DNA Oxidative Damages,Damage, DNA Oxidative,Damage, Oxidative,Damage, Oxidative DNA,Injury, Oxidative,Injury, Oxidative Stress,Nitrative Stress, Oxidative,Nitro Oxidative Stress,Nitro-Oxidative Stresses,Oxidative Cleavages,Oxidative DNA Damages,Oxidative Damage, DNA,Oxidative Damages,Oxidative Injuries,Oxidative Nitrative Stresses,Oxidative Stress Injuries,Oxidative Stresses,Stress Injury, Oxidative,Stress, Anti-oxidative,Stress, Antioxidative,Stress, Nitro-Oxidative,Stress, Oxidative Nitrative,Stresses, Nitro-Oxidative

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