Evidence that ultrafine titanium dioxide induces micronuclei and apoptosis in Syrian hamster embryo fibroblasts.

Abstract

Inhaled ultrafine titanium dioxide (UF-TiO2) particles cause pronounced pulmonary inflammation, in contrast to fine TiO2. Previous studies provide evidence for the production of reactive oxygen species by alveolar macrophages, after overloading with UF-TiO2 particles and cytotoxicity of UF-TiO2 in rat lung alveolar macrophages. UF-TiO2 also causes pulmonary fibrosis and lung tumors in rats. UF-TiO2 particles are photogenotoxic, but in general, information on the genotoxicity of UF-TiO2 is still limited. We studied the potential of UF-TiO2 (particle size less than or equal to 20 nm) and fine TiO2 (particle size > 200 nm) to induce chromosomal changes, which can be monitored by the formation of micronuclei (MN) in Syrian hamster embryo (SHE) cells. We also analyzed UF-TiO2-treated cells for apoptosis induction. The MN assay revealed a significant increase in MN induction (p less than or equal to 0.05) in SHE cells after treatment with UF-TiO2 (1.0 micro g/cm2) for 12 hr (mean, 24.5 MN/1,000 cells), 24 hr (mean, 31.13 MN/1,000 cells), 48 hr (mean, 30.8 MN/1,000 cells), 66 hr (mean, 31.2 MN/1,000 cells), and 72 hr (mean, 31.3 MN/1,000 cells). Bisbenzimide staining of the fixed cells revealed typical apoptotic structures (apoptotic bodies), and the apoptosis-specific "DNA ladder pattern" resulting from internucleosomal cleavage was identified by gel electrophoresis. Furthermore, transmission electron microscopy of the exposed cells revealed the typical chromatin compaction of apoptosis.

In vitro cytotoxicity and genotoxicity studies of titanium dioxide (TiO2) nanoparticles in Chinese hamster lung fibroblast cells

“…Recent studies have reported chromosomal damage induced by nano-TiO 2 in hamster embryo fibroblasts, blood lymphocytes, and in a human B-cell lymphoblastoid cell line using the micronucleus assay (Kang et al, 2008;Rahman et al, 2002;Wang et al, 2007), which was mostly associated with ROS-related DNA injury. Similarly, an in vivo study has shown the induction of DNA breakage in mice cells after exposure to P25-TiO 2 in drinking water (Trouiller et al, 2009).…”

In vitro studies on chemoprotective effect of borax against aflatoxin B1-induced genetic damage in human lymphocytes

“…However, depletion of GSH leads to oxidative stress. The decrease in cellular glutathione content can affect signaling pathways that participate in various physiological responses from cell proliferation to gene expression (Rahman et al 2002). Thus, it is possible that AFB1-induced oxidative stress acted as an intermediate for the observed genetic damage.…”

In vitro tagging of embryos with nanoparticles

“…Studies in other cell types have shown that internalized nanoparticles [7] derived from materials other than that tested here disrupted fibroblast and cancer cells after adhering to the cell membranes, impaling and/or releasing toxic ions [27][28][29][30][31][32]. Moreover, nanoparticles internalized into cells increased the reactive oxygen species (ROS), elevated intracellular calcium, activated transcription factors [10] and initiated apoptosis or cell death [14]. Although these events have not been reported for embryos, the possibility exists that specific nanomaterials may interfere with the further development of the blastocysts.…”

“…A nanoparticle or ultrafine particle has a particle mass of less than 100 nm in diameter. Nanoparticles are made from materials such as cadmium selenide [4,5], gold [6], silver [7], perylene [8], polystyrene [9], carbon [10,11], iron oxide [12], silica [13], titanium dioxide [14]. Some types of nanoparticles are organic-based such as latex [15], polylactic acid [16], polyglycolic acid [17] and polyalkylcyanoacrylate [18] while others are based on carbon, sulfates, nitrates [19,20], aluminum, silicon, or titanium [21].…”