Journal
ACS NANO
Volume 5, Issue 9, Pages 7284-7295Publisher
AMER CHEMICAL SOC
DOI: 10.1021/nn202116p
Keywords
high content imaging; transition metal oxide nanoparticle; dissolution; hsp70; zebrafish; hazard ranking
Categories
Funding
- National Science Foundation
- Environmental Protection Agency [DBI 0830117]
- U.S. Public Health Service [RO1 CA133697, RO1 ES016746, RC2 ES018766, U19 ES019528]
- Div Of Biological Infrastructure
- Direct For Biological Sciences [0830117] Funding Source: National Science Foundation
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Zebrafish is an aquatic organism that can be used for high content safety screening of engineered nanomaterials (ENMs). We demonstrate, for the first time, the use of high content bright-field and fluorescence-based imaging to compare the toxicological effect of transition metal oxide (CuO, ZnO, NiO, and Co3O4) nanoparticles in zebrafish embryos and larvae. High content bright-field imaging demonstrated potent and dose-dependent hatching interference in the embryos, with the exception of Co3O4 which was relatively inert. We propose that the hatching interference was due to the shedding of Cu and Ni ions, compromising the activity of the hatching enzyme, ZHE1, similar to what we previously proposed for Zn2+. This hypothesis is based on the presence of metal-sensitive histidines in the catalytic center of this enzyme. Co-introduction of a metal ion chelator, diethylene triamine pentaacetic acid (DTPA), reversed the hatching interference of Cu, Zn, and Ni. While neither the embryos nor larvae demonstrated morphological abnormalities, high content fluorescence-based imaging demonstrated that CuO ZnO, and NiO could induce increased expression of the heat shock protein 70:enhanced green fluorescence protein (hsp70:eGFP) in transgenic zebrafish larvae. Induction of this response by CO required a higher nanoparticle dose than the amount leading to hatching interference. This response was also DTPA-sensitive. We demonstrate that high content imaging of embryo development, morphological abnormalities, and HSP70 expression can be used for hazard ranking and determining the dose response relationships leading to ENM effects on the development of the zebrafish embryo.
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