Michael J Burgum, Stephen J Evans, Ilaria Zanoni, Magda Blosi, Gareth J Jenkins, Shareen H Doak
{"title":"Tungsten carbide-cobalt can function as a particle positive control for genotoxicity in vitro in specific cell lines.","authors":"Michael J Burgum, Stephen J Evans, Ilaria Zanoni, Magda Blosi, Gareth J Jenkins, Shareen H Doak","doi":"10.1093/mutage/geaf021","DOIUrl":null,"url":null,"abstract":"<p><p>Nanoparticle genotoxicity can be induced through several mechanisms, but there are currently no nanoparticle positive controls available for the evaluation of in vitro genotoxicity. Tungsten carbide-cobalt (WC/Co) has been proposed as one possible candidate. The aim of this study was therefore to investigate the genotoxic profile of WC/Co (Co 8% wt.) utilising the cytokinesis-blocked micronucleus (CBMN) assay, the mammalian cell gene mutation test, and comet assay following a 24-hour exposure. This was conducted in human lymphoblast (TK6) and Chinese hamster lung fibroblast (V79-4) cells. No cytotoxicity was observed in the TK6 CBMN assay even when significant induction of micronuclei was observed at 100 μg/ml (2-fold over control). In contrast, V79-4 cells demonstrated no significant genotoxicity or cytotoxicity in the CBMN assay. In the gene mutation assay significant mutagenicity was observed in V79-4 cells at 100 μg/ml (2-fold over control). Cellular uptake of the WC/Co nanoparticles was not qualitatively detected in either cell type when investigated with transmission electron microscopy (TEM). No genotoxicity was observed in either cell type with the comet assay. The data generated indicates that WC/Co nanoparticles may be used as a positive particulate control in the CBMN assay when using TK6 cells only; whilst in the gene mutation assay it can be used as a positive control for V79-4 cells. However, its use as a particle positive control is only possible when applying the highest test concentration of 100 μg/ml.</p>","PeriodicalId":18889,"journal":{"name":"Mutagenesis","volume":" ","pages":""},"PeriodicalIF":4.3000,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Mutagenesis","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1093/mutage/geaf021","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"GENETICS & HEREDITY","Score":null,"Total":0}
引用次数: 0
Abstract
Nanoparticle genotoxicity can be induced through several mechanisms, but there are currently no nanoparticle positive controls available for the evaluation of in vitro genotoxicity. Tungsten carbide-cobalt (WC/Co) has been proposed as one possible candidate. The aim of this study was therefore to investigate the genotoxic profile of WC/Co (Co 8% wt.) utilising the cytokinesis-blocked micronucleus (CBMN) assay, the mammalian cell gene mutation test, and comet assay following a 24-hour exposure. This was conducted in human lymphoblast (TK6) and Chinese hamster lung fibroblast (V79-4) cells. No cytotoxicity was observed in the TK6 CBMN assay even when significant induction of micronuclei was observed at 100 μg/ml (2-fold over control). In contrast, V79-4 cells demonstrated no significant genotoxicity or cytotoxicity in the CBMN assay. In the gene mutation assay significant mutagenicity was observed in V79-4 cells at 100 μg/ml (2-fold over control). Cellular uptake of the WC/Co nanoparticles was not qualitatively detected in either cell type when investigated with transmission electron microscopy (TEM). No genotoxicity was observed in either cell type with the comet assay. The data generated indicates that WC/Co nanoparticles may be used as a positive particulate control in the CBMN assay when using TK6 cells only; whilst in the gene mutation assay it can be used as a positive control for V79-4 cells. However, its use as a particle positive control is only possible when applying the highest test concentration of 100 μg/ml.
期刊介绍:
Mutagenesis is an international multi-disciplinary journal designed to bring together research aimed at the identification, characterization and elucidation of the mechanisms of action of physical, chemical and biological agents capable of producing genetic change in living organisms and the study of the consequences of such changes.