| dc.description |
Due to their unique physical, chemical, and magnetic properties, nanomaterials have
great potential for industrial development. There is a pressing need to develop rapid
whole animal-based testing assays to assess the potential toxicity of engineered
nanomaterials. To meet this challenge the embryonic zebrafish model was employed to
determine the toxicity of fullerenes. Embryonic zebrafish were exposed to graded
concentrations of C₆₀, C₇₀, and C₆₀(OH)₂₄ during early embryogenesis and evaluated for
morphological and behavioral responses. Exposure to C₆₀ and C₇₀ induced a significant
increase in malformations, pericardial edema, and mortality; while the response to
C₆₀(OH)₂₄ exposure was less pronounced at concentrations an order of magnitude higher.
Cell death was determined to be the most sensitive physiologic response. Oxidative
stress was examined as a mechanism through which C₆₀ elicited a response. This was
probed through chemical manipulation of glutathione and antioxidant levels. Finally, the global gene expression following C₆₀ exposure was evaluated. These results further
implicate glutathione depletion as a result of oxidative stress as a mechanism of action.
Analytical chemistry methods were developed to determine the dose of C₆₀ that induced
toxicity in zebrafish embryos. These results indicate only a small portion of C₆₀ in the
water was actually absorbed by the embryo to elicit a response. The versatility and
efficiency of the embryonic zebrafish model demonstrated its usefulness for screening
nanomaterials for toxicity as well as a model organism for probing pathways through
which a nanomaterial may elicit a toxic response. |
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