Document Detail


Evaluation of the apoptogenic potential of hard metal dust (WC-Co), tungsten carbide and metallic cobalt.
MedLine Citation:
PMID:  15475175     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The present study aimed at comparing in vitro the apoptogenic properties of metallic cobalt (Co), tungsten carbide (WC) and tungsten carbide-cobalt (WC-Co) in conditions known to cause genotoxicity. Human peripheral blood mononucleated cells were incubated with 2.0-6.0 microg/ml of Co alone or mixed with WC particles and 33.3-100.0 microg/ml WC alone for up to 24 h. Under these culture conditions the majority (60%) of the cobalt metal particles were almost immediately solubilised in the culture medium, while WC remained under the form of particles that were progressively phagocytosed by monocytes. Apoptosis was assessed by Annexin-V staining, flow cytometry and analysis of DNA fragmentation by ELISA. Metallic Co-particles induced apoptosis in vitro. Furthermore, although so far considered as biologically inert, WC particles also induced apoptosis. When compared with its individual components WC-Co displayed an additive apoptotic effect in the DNA fragmentation assay. Apoptosis induced by WC particles was found largely dependent on caspase-9 activation and occurred presumably in monocytes, while that induced by Co involved both caspase-9 and -8 activation. The data suggest that apoptosis induced by the tested WC-Co mixture results from the additive effects of WC apoptosis induced in monocytes and Co-specific apoptosis in both monocytes and lymphocytes. The apoptogenic properties of these metals may be important in the mechanism of lung pathologies induced by the cobalt-containing particles.
Authors:
Noömi Lombaert; Marlies De Boeck; Ilse Decordier; Enrico Cundari; Dominique Lison; Micheline Kirsch-Volders
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Toxicology letters     Volume:  154     ISSN:  0378-4274     ISO Abbreviation:  Toxicol. Lett.     Publication Date:  2004 Dec 
Date Detail:
Created Date:  2004-10-11     Completed Date:  2004-11-16     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  7709027     Medline TA:  Toxicol Lett     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  23-34     Citation Subset:  IM    
Affiliation:
Laboratorium voor Cellulaire Genetica, Vrije Universiteit Brussel, Pleinlaan 2, B-1050 Brussel, Belgium. nlombaer@vub.ac.be
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MeSH Terms
Descriptor/Qualifier:
Annexin A5 / metabolism
Apoptosis / drug effects*
Caspases / biosynthesis
Cells, Cultured
Cobalt / toxicity*
DNA Fragmentation
Dose-Response Relationship, Drug
Drug Combinations
Enzyme-Linked Immunosorbent Assay
Flow Cytometry
Humans
Leukocytes, Mononuclear / drug effects*,  metabolism,  ultrastructure
Microscopy, Electron
Monocytes / drug effects,  enzymology,  pathology
Tungsten Compounds / toxicity*
Chemical
Reg. No./Substance:
0/Annexin A5; 0/Drug Combinations; 0/Tungsten Compounds; 11130-73-7/tungsten carbide; 7440-48-4/Cobalt; EC 3.4.22.-/Caspases

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