Abstract
BackgroundTungsten carbide (WC) and tungsten carbide cobalt (WC-Co) nanoparticles are of occupational health relevance because of the increasing usage in hard metal industries. Earlier studies showed an enhanced toxic potential for WC-Co compared to WC or cobalt ions alone. Therefore, we investigated the impact of these particles, compared to cobalt ions applied as CoCl2, on the global gene expression level in human keratinocytes (HaCaT) in vitro.ResultsWC nanoparticles exerted very little effects on the transcriptomic level after 3 hours and 3 days of exposure. In contrast, WC-Co nanoparticles caused significant transcriptional changes that were similar to those provoked by CoCl2. However, CoCl2 exerted even more pronounced changes in the transcription patterns. Gene set enrichment analyses revealed that the differentially expressed genes were related to hypoxia response, carbohydrate metabolism, endocrine pathways, and targets of several transcription factors. The role of the transcription factor HIF1 (hypoxia inducible factor 1) is particularly highlighted and aspects of downstream events as well as the role of other transcription factors related to cobalt toxicity are considered.ConclusionsThis study provides extensive data useful for the understanding of nanoparticle and cobalt toxicity. It shows that WC nanoparticles caused low transcriptional responses while WC-Co nanoparticles are able to exert responses similar to that of free cobalt ions, particularly the induction of hypoxia-like effects via interactions with HIF1α in human keratinocytes. However, the enhanced toxicity of WC-Co particles compared to CoCl2 could not be explained by differences in gene transcription.
Highlights
Tungsten carbide (WC) and tungsten carbide cobalt (WC-Co) nanoparticles are of occupational health relevance because of the increasing usage in hard metal industries
It shows that WC nanoparticles caused low transcriptional responses while WC-Co nanoparticles are able to exert responses similar to that of free cobalt ions, the induction of hypoxia-like effects via interactions with HIF1a in human keratinocytes
In a previous study [21] we have investigated the impact of WC and WC-Co nanoparticles on the vitality of various mammalian cells
Summary
Tungsten carbide (WC) and tungsten carbide cobalt (WC-Co) nanoparticles are of occupational health relevance because of the increasing usage in hard metal industries. Engineered nanomaterials are used in large amounts in several industries and an increasing demand, including new types of particles, is anticipated in the future [1]. Their physico-chemical properties, i.e. the small size and the high surface to volume ratio are one of the most interesting characteristics, which is useful for many applications in medicine, chemistry, material sciences and physics. Griffitt and colleagues [11] showed that metal ions (silver and copper) caused similar expression patterns as nanoparticles of the same materials in zebrafish, but the numbers of affected genes were always higher after exposure to the particles. The majority of biological processes represented by the differentially expressed genes were nearly identical, irrespective of particle diameter
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