Tungsten carbide-cobalt as a nanoparticulate reference positive control in in vitro genotoxicity assays.

Abstract

With the increasing human exposure to nanoparticles (NP), the evaluation of their genotoxic potential is of significant importance. However, relevance for NP of the routinely used in vitro genotoxicity assays is often questioned, and a nanoparticulate reference positive control would therefore constitute an important step to a better testing of NP, ensuring that test systems are really appropriate. In this study, we investigated the possibility of using tungsten carbide-cobalt (WC-Co) NP as reference positive control in in vitro genotoxicity assays, including 2 regulatory assays, the mouse lymphoma assay and the micronucleus assay, and in the Comet assay, recommended for the toxicological evaluation of nanomedicines by the French Agency of Human Health Products (Afssaps). Through these assays, we were able to study different genetic endpoints in 2 cell types commonly used in regulatory genotoxicity assays: the L5178Y mouse lymphoma cell line and primary cultures of human lymphocytes. Our results showed that the use of WC-Co NP as positive control in in vitro genotoxicity assays was conceivable, but that different parameters have to be considered, such as cell type and treatment schedule. L5178Y mouse lymphoma cells did not provide satisfactory results in the 3 performed tests. However, human lymphocytes were more sensitive to genotoxic effects induced by WC-Co NP, particularly after a 24-h treatment in the in vitro micronucleus assay and after a 4-h treatment in the in vitro Comet assay. Under such conditions, WC-Co could be used as a nanoparticulate reference positive control in these assays.

• Authors: Hélène Moche, Dany Chevalier, Nicolas Barois, Elisabeth Lorge, Nancy Claude, Fabrice Nesslany
• Journal: Toxicological sciences : an official journal of the Society of Toxicology (Toxicol Sci) Vol. 137 Issue 1 Pg. 125-34 (Jan 2014) ISSN: 1096-0929 [Electronic] United States
• PMID: 24085191 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Tungsten Compounds
• tungsten carbide
• Cobalt

Topics

• Adult
• Animals
• Cell Line, Tumor
• Cobalt (toxicity)
• Comet Assay (standards)
• Dose-Response Relationship, Drug
• Female
• Humans
• Lymphocytes (drug effects, metabolism, pathology)
• Lymphoma (genetics, metabolism, pathology)
• Male
• Metal Nanoparticles (toxicity)
• Mice
• Micronuclei, Chromosome-Defective (chemically induced)
• Micronucleus Tests (standards)
• Mutagenicity Tests (standards)
• Reference Standards
• Tungsten Compounds (toxicity)