title: Cytotoxic, genotoxic and the hemolytic effect of titanium dioxide (TiO2 ) nanoparticles on human erythrocyte and lymphocyte cells in vitro.
abstract: With the increasing clinical use of titanium dioxide (TiO2 ) nanoparticles, a better understanding of their safety in the blood stream is required. The present study evaluates the toxic effect of commercially available TiO2 nanoparticles (~100 nm) using a battery of cytotoxic, genotoxic, hemolytic and morphological parameters. The cytotoxic effects of TiO2 nanoparticles in human lymphocyte cells were studied with respect to membrane damage, mitochondrial function, metabolic activity and lysosomal membrane stability. Genotoxicity in lymphocyte cells was quantitated using a comet assay. The mode of cell death (apoptosis/necrosis) was evaluated using PI/Annexin V staining. TiO2 nanoparticles were also evaluated for their hemolytic properties, osmotic fragility and interaction with hemoglobin. Human erythrocyte cells were studied for morphological alterations using atomic force microscopy (AFM). Results suggest that the particles could induce a significant reduction in mitochondrial dehydrogenase activity in human lymphocyte cells. Membrane integrity remained unaffected by nanoparticle treatment. DNA damage and apoptosis were induced by TiO2 nanoparticles in a dose-dependent manner. A study on human erythrocyte cells revealed a hemolytic property of TiO2 nanoparticles characterized by spherocytosis and echinocytosis. Spectral analysis revealed a hemoglobin TiO2 nanoparticle interaction. Our in vitro study results suggest that commercially available blood contacting nanoparticles (TiO2 nanoparticle) should be carefully evaluated for their toxic potential.
authors.affiliation: Cell Biology and Genetic Toxicology Laboratory, Centre of Advanced Study, Department of Botany, University of Calcutta, Kolkata, India.
authors.forename: Manosij
authors.initials: M
authors.lastname: Ghosh
authors.forename: Anirban
authors.initials: A
authors.lastname: Chakraborty
authors.forename: Anita
authors.initials: A
authors.lastname: Mukherjee
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D020552:Comet Assay; D004249:DNA Damage / Q000187:drug effects*; D004912:Erythrocytes / Q000166:cytology / Q000187:drug effects*; D006461:Hemolysis; D006801:Humans; D008214:Lymphocytes / Q000166:cytology / Q000187:drug effects*; D053768:Metal Nanoparticles / Q000737:chemistry / Q000633:toxicity*; D046529:Microscopy, Electron, Transmission; D009336:Necrosis / Q000139:chemically induced; D010316:Particle Size; D017382:Reactive Oxygen Species; D014025:Titanium / Q000737:chemistry / Q000633:toxicity*
chemical_list: D017382:Reactive Oxygen Species; C009495:titanium dioxide; D014025:Titanium
keywords: atomic force microscopy; cytotoxicity; echinocyte; genotoxicity; hemolysis; reactive oxygen species