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Little is known about the biological effects of metals on adult stem/progenitor cells, which play key roles in tissue homeostasis and repair. We recently reported that autophagy is a prominent response of hematopoietic stem/progenitor cells to toxic concentrations of hexavalent chromium (Cr[VI]) and cadmium (Cd), two well known carcinogenic heavy metal cations. No data exhist on the effects of nanoparticles. We investigated the biological responses to particulated metals, that could be modulated by particle size, type and release of metal ions.
Methods
To gain insight into the acute biological effects of particulated versus solubilized metals we used cDNA microarrays to screen differences in gene expression after exposure to cobalt ions or cobalt nano- and micro-particles in the BALB3T3 A31-1-1 murine cell model. Changes in gene expression induced after 72 h exposure to cobalt microparticles, cobalt nanoparticles and cobalt ions (0.2-0.8mM) were assessed using murine whole genome arrays.
Results
Using gold, we found that metal particles were readily internalized by human cord blood hematopoietic stem/progenitor cells, distributing to all subcellular compartments, including nucleus. Selected gene expression changes were confirmed by real-time PCR. Several gene classes were modulated, and, most notably, differences related to type of exposure emerged. Modulation of Rab18, a gene that regulates secretory pathways, was common to all forms of exposure. Microparticles and nanoparticles differentially modulated genes involved in defense and repair pathways: genes in the interferon, apoptosis, JAK/STAT and death receptor signaling pathways were modulated by nanoparticles; genes implicated in nucleotide sugar metabolism, G1/S cell cycle checkpoint regulation, hypoxia signalling and protein ubiquitination pathways by microparticles.
Discussion
Nanoparticles can have different toxicological effects than micro particles and ion of the corresponding metal