Tungsten carbide-cobalt can function as a particle positive control for genotoxicity in vitro in specific cell lines.

IF 4.3 4区 医学 Q3 GENETICS & HEREDITY
Mutagenesis Pub Date : 2025-10-03 DOI:10.1093/mutage/geaf021
Michael J Burgum, Stephen J Evans, Ilaria Zanoni, Magda Blosi, Gareth J Jenkins, Shareen H Doak
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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.

碳化钨钴可作为特定细胞系体外遗传毒性的颗粒阳性对照物。
纳米颗粒遗传毒性可通过多种机制诱导,但目前还没有纳米颗粒阳性对照物可用于体外遗传毒性评价。碳化钨-钴(WC/Co)被认为是一种可能的候选材料。因此,本研究的目的是利用细胞分裂阻断微核(CBMN)测定、哺乳动物细胞基因突变试验和暴露24小时后的彗星测定来研究WC/Co (Co 8% wt.)的遗传毒性谱。这是在人淋巴母细胞(TK6)和中国仓鼠肺成纤维细胞(V79-4)细胞中进行的。在TK6 CBMN实验中,即使在100 μg/ml(2倍于对照)的浓度下观察到微核的显著诱导,也未观察到细胞毒性。相比之下,V79-4细胞在CBMN实验中没有表现出明显的遗传毒性或细胞毒性。在基因突变实验中,100 μg/ml的剂量对V79-4细胞有显著的致突变性(2倍于对照组)。在透射电子显微镜(TEM)下,两种细胞类型均未定性检测到WC/Co纳米颗粒的细胞摄取。彗星试验在两种细胞类型中均未观察到遗传毒性。所产生的数据表明,当仅使用TK6细胞时,WC/Co纳米颗粒可以用作CBMN试验中的阳性颗粒对照;而在基因突变试验中,它可以作为V79-4细胞的阳性对照。然而,只有在最高检测浓度为100 μg/ml时,才有可能将其用作颗粒阳性对照。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Mutagenesis
Mutagenesis 生物-毒理学
CiteScore
5.90
自引率
3.70%
发文量
22
审稿时长
6-12 weeks
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.
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