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Toxicity of metal and metal oxide nanoparticles in developing zebrafish

Posted on:2012-09-01Degree:Ph.DType:Dissertation
University:The University of Wisconsin - MadisonCandidate:Bar-Ilan, OfekFull Text:PDF
GTID:1451390008998031Subject:Health Sciences
Abstract/Summary:
There is an immediate need to assess nanomaterials' potential toxicities due to exponential growth of use, characteristics that differ from bulk materials, and uncertainties about interactions with biological entities. We chose developing zebrafish for these toxicity studies because of their well-characterized genetics, rapid development, and transparency. Many published reports claim that metal nanoparticle toxicity is size-dependent, but fail to acknowledge that chemical composition may be crucial in inducing toxicity as well. To reconcile the size-composition debate, we exposed zebrafish embryos to multiple metals (silver and gold) and sizes (3, 10, 50, and 100 nm) of nanoparticles. We found that nanoparticle composition is as important, if not more so, than specific sizes at inducing toxicity in vivo, with silver being more toxic than gold in all sizes tested. Also of interest is how environmental conditions, like sunlight, could alter nanoparticle behavior and toxicity. To study this, we chose titanium dioxide nanoparticles (TiO2NPs) for their photocatalytic property—a property that makes them useful, but which we thought would also be the key in predicting their biological impact. TiO2NPs absorb photons with energy equal to or larger than their band gap (e.g., shorter-wavelength light reaching Earth's surface), which leads to separated electron-hole pairs. Separated electrons and holes can generate reactive oxygen species (ROS) that indiscriminately damage cellular macromolecules, eventually leading to cellular death through oxidative stress. Therefore, we hypothesized that upon illumination with light of energy exceeding the band gap, TiO2NPs would induce oxidative toxicity in developing zebrafish. Embryos were exposed to commercially available TiO2NPs with and without illumination for five days. In this acute study, we found that mortality was photo- and dose-dependent, and that toxicity was caused by oxidative stress. Because cellular damage produced by ROS can be continuous and cumulative, we expected that given more time, lower more environmentally relevant concentrations of illuminated TiO 2NPs would produce enough oxidative damage to manifest as toxic responses. Two commercial brands of TiO2NPs were applied subchronically for 23 days during embryolarval development and metamorphosis into the adult form. Both TiO2NP brands produced photodependent toxicity at concentrations as low as the environmentally relevant 1 ng/ml.
Keywords/Search Tags:Toxicity, Metal, Nanoparticles, Developing, Zebrafish
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