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Title: Toxicogenomics of synthetic and natural nanoparticles in the nematode C. elegans
Author: Polak, Natasa
ISNI:       0000 0004 5357 5617
Awarding Body: King's College London (University of London)
Current Institution: King's College London (University of London)
Date of Award: 2014
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Natural and synthetic nanoparticles (NP) are microscopic particles, which are characterized by their small size (< 0.1 μm). It is now well established that exposure to NPs can represent a serious risk to human health and the environment. To establish the modes of action of NP toxicity, this project utilizes the nematode Caenorhabditis elegans to conduct baseline studies to screen the toxicological effects (on life-history traits, fitness, and metabolism) of metal oxide based synthetic (30 nm ZnONPs), and naturally occurring (Carbon Black M120 and NIST 1648a) NPs. The results indicate that: 1) The Nanosight NTA technique is a suitable tool to evaluate particle aggregation in biological test media. 2) All tested particles exert a shared toxic response that is manifested by a decrease in reproductive potential. The toxic effects were dose responsive to ZnONPs exposure, but not to NIST and CB. 3) The DCFH-DA assay provided in vitro evidence of the oxidative potential of particles, as the intracellular total ROS levels were altered. 4) The whole genome, qPCR analyses, and microscopy provided evidence that the majority of transcripts involved in stress response pathways (e.g. sod family; cat-2,-3; hsp-16.1) did not alter or were only marginally affected by the particles. Nevertheless, the most profound effects were the down regulation of the ribosomal RNA transcript (rrn-3.1) with increasing NIST concentrations, and the induction of cep-1 gene (p53 human orthologous) with ZnONPs. 5) Finally, spectroscopic strategies identified the importance of metallochelators in the protection from ZnONP induced toxicity. Overall, the results of this study suggest that the use of sensitive nematode mutants combined with genomic tools represents a powerful approach to assess the physicochemical toxicity of different types of particles.
Supervisor: Sturzenbaum, Stephen Richard; Kelly, Frank James Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available