In many studies, upon TiO 2 nanoparticle exposure, damage to lipids, proteins, and DNA leads to damage of subcellular organelles and cell death –. However, conflicting observations have made it difficult to establish a detailed molecular mechanism of TiO 2 nanoparticle cytotoxicity. In vitro experiments involving the effects of TiO 2 nanoparticles on various cell lines have generally confirmed the results obtained from animal studies. The cytotoxic effects of TiO 2 nanoparticles depend on physicochemical properties of TiO 2 nanoparticles, particularly their size, with smaller particles causing more damage than bigger ones. Similarly, oral delivery of TiO 2 nanoparticles leads to inflammation and damage to liver and kidney. For instance, intratracheal instillation of TiO 2 nanoparticles in mice causes pulmonary inflammation, emphysema, and epithelial cell apoptosis. Research on animal models has further confirmed the cytotoxic effects of TiO 2 nanoparticles. Through inhalation, ingestion, and injection, TiO 2 nanoparticles can enter the human body, where they may interact with cells and components of cells, such as proteins and lipids, to compromise cellular functions, leading to cell toxicity –. Emerging evidence suggests that the unique physical and chemical properties of TiO 2 nanoparticles, such as ultra-small size, increased surface area per unit mass, chemical composition, surface structure, shape, aggregation, and high reactivity, may pose potential risks to human health and the environment. Titanium dioxide (TiO 2) nanoparticles have a wide range of commercial applications, particularly in consumer products. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Ĭompeting interests: The authors have declared that no competing interests exist. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.įunding: This study was supported by National Institutes of Health (NIH) grants CA106599, RR018733 and funding from the Kentucky Lung Cancer Research Program and the University of Louisville (CL) and NIH grant AA018016 and the Commonwealth of Kentucky Research Challenge Trust Fund (JWE). Received: AugAccepted: OctoPublished: November 21, 2012Ĭopyright: © 2012 Zhu et al. Roswell Park Cancer Institute, United States of America Overall, our data indicate that TiO 2 nanoparticles induce cytotoxicity preferentially in transformed cells independent of a major apoptotic signaling pathway.Ĭitation: Zhu Y, Eaton JW, Li C (2012) Titanium Dioxide (TiO 2) Nanoparticles Preferentially Induce Cell Death in Transformed Cells in a Bak/Bax-Independent Fashion.
Because transformation does not affect cellular fluid-phase endocytosis or nanoparticle uptake, it is likely that the increased cytotoxicity in tumor cells is due to the interaction between TiO 2 nanoparticles and the lysosomal compartment. Importantly, the elevated cytotoxicity of TiO 2 nanoparticles was independent of a major Bak/Bax-dependent apoptosis pathway. TiO 2 nanoparticles preferentially reduced viability of tumorigenic cells in a dose-dependent fashion compared with their untransformed counterparts. Isogenic wild-type (WT) and apoptosis-resistant (Bak −/−Bax −/−) cell lines with and without tumorigenic transformation were examined. Here we investigated the influence of oncogenic transformation and a major apoptotic signaling pathway on cellular responses to TiO 2 nanoparticles.
While the cytotoxic effects of titanium dioxide (TiO 2) nanoparticles have been under intense investigation, the molecular mechanisms of this cytotoxicity remain unknown.
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