title: Tungsten carbide cobalt nanoparticles exert hypoxia-like effects on the gene expression level in human keratinocytes.
abstract: BACKGROUND
  Tungsten 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 CoCl(2), on the global gene expression level in human keratinocytes (HaCaT) in vitro.
  
  
  RESULTS
  WC 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 CoCl(2). However, CoCl(2) 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.
  
  
  CONCLUSIONS
  This 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 HIF1alpha in human keratinocytes. However, the enhanced toxicity of WC-Co particles compared to CoCl(2) could not be explained by differences in gene transcription.
authors.affiliation: UFZ - Helmholtz-Centre for Environmental Research Leipzig, Department of Bioanalytical Ecotoxicology, 04318 Leipzig, Germany. wibke.busch@ufz.de
authors.forename: Wibke
authors.initials: W
authors.lastname: Busch
authors.forename: Dana
authors.initials: D
authors.lastname: Kühnel
authors.forename: Kristin
authors.initials: K
authors.lastname: Schirmer
authors.forename: Stefan
authors.initials: S
authors.lastname: Scholz
mesh_terms: D050260:Carbohydrate Metabolism; D015687:Cell Hypoxia; D002460:Cell Line; D016000:Cluster Analysis; D003035:Cobalt / Q000633:toxicity; D020869:Gene Expression Profiling; D006801:Humans; D051793:Hypoxia-Inducible Factor 1 / Q000378:metabolism; D015603:Keratinocytes / Q000187:drug effects* / Q000378:metabolism; D053758:Nanoparticles / Q000633:toxicity*; D020411:Oligonucleotide Array Sequence Analysis; D025341:Principal Component Analysis; D015398:Signal Transduction; D017973:Tungsten Compounds / Q000633:toxicity*
chemical_list: D051793:Hypoxia-Inducible Factor 1; D017973:Tungsten Compounds; C002802:tungsten carbide; D003035:Cobalt; C018021:cobaltous chloride