Abstract

We utilized size-tunable gold nanoparticles (Au NPs) to investigate the toxicogenomic responses of the model organism Caenorhabditis elegans. We demonstrated that the nematode C. elegans can uptake Au NPs coated with or without 11-mercaptoundecanoic acid (MUA), and Au NPs are detectable in worm intestines using X-ray microscopy and confocal optical microscopy. After Au NP exposure, C. elegans neurons grew shorter axons, which may have been related to the impeded worm locomotion behavior detected. Furthermore, we determined that MUA to Au ratios of 0.5, 1 and 3 reduced the worm population by more than 50% within 72 hours. In addition, these MUA to Au ratios reduced the worm body size, thrashing frequency (worm mobility) and brood size. MTT assays were employed to analyze the viability of cultured C. elegans primary neurons exposed to MUA-Au NPs. Increasing the MUA to Au ratios increasingly reduced neuronal survival. To understand how developmental changes (after MUA-Au NP treatment) are related to changes in gene expression, we employed DNA microarray assays and identified changes in gene expression (e.g., clec-174 (involved in cellular defense), cut-3 and fil-1 (both involved in body morphogenesis), dpy-14 (expressed in embryonic neurons), and mtl-1 (functions in metal detoxification and homeostasis)).

Highlights

  • Bare Au and mercaptoundecanoic acid (MUA)-Au NPs were synthesized by intense X-ray irradiation as described previously[13]. This method provides a simple and rapid procedure to reduce Au ions into Au NPs and further control the size of MUA-Au NPs produced by X-ray irradiation[13]

  • Note that MUA plays an important role in terminating the nucleation and growth of Au NPs due to its high affinity for Au

  • The process of reducing Au ions into Au NPs occurs in the subsecond range and is independent of the MUA concentration, allowing accurate particle size control

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Summary

Introduction

Affecting motor neuron function (indicated by changes in animal mobility), remains unclear. Primary neurons can be isolated from C. elegans embryos and cultured for several days at room temperature without adjusting the CO2 atmosphere. This straightforward protocol enables the determination of developmental changes in neurons (e.g., axon growth) upon MUA-Au NP exposure. We investigated how Au NP uptake affects gene regulation in nematodes by employing commercially available DNA microarray gene chips. With this assay, changes in the expression of 22,548 C. elegans genes (with high homology to human genes) were detected by comparing control animals and Au NP-treated animals

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