Williams Andrew, Buick Julie K, Moffat Ivy, Swartz Carol D, Recio Leslie, Hyduke Daniel R, Li Heng-Hong, Fornace Albert J, Aubrecht Jiri, Yauk Carole L
Environmental Health Science and Research Bureau, Health Canada, Ottawa, Ontario, Canada K1A 0K9.
Environmental Health Science and Research Bureau, Health Canada, Ottawa, Ontario, Canada K1A 0K9 ; Water and Air Quality Bureau, Health Canada, Ottawa, Ontario, Canada K1A 0K9.
Data Brief. 2015 Aug 24;5:77-83. doi: 10.1016/j.dib.2015.08.013. eCollection 2015 Dec.
Genotoxicity testing is a critical component of chemical assessment. The use of integrated approaches in genetic toxicology, including the incorporation of gene expression data to determine the DNA damage response pathways involved in response, is becoming more common. In companion papers previously published in Environmental and Molecular Mutagenesis, Li et al. (2015) [6] developed a dose optimization protocol that was based on evaluating expression changes in several well-characterized stress-response genes using quantitative real-time PCR in human lymphoblastoid TK6 cells in culture. This optimization approach was applied to the analysis of TK6 cells exposed to one of 14 genotoxic or 14 non-genotoxic agents, with sampling 4 h post-exposure. Microarray-based transcriptomic analyses were then used to develop a classifier for genotoxicity using the nearest shrunken centroids method. A panel of 65 genes was identified that could accurately classify toxicants as genotoxic or non-genotoxic. In Buick et al. (2015) [1], the utility of the biomarker for chemicals that require metabolic activation was evaluated. In this study, TK6 cells were exposed to increasing doses of four chemicals (two genotoxic that require metabolic activation and two non-genotoxic chemicals) in the presence of rat liver S9 to demonstrate that S9 does not impair the ability to classify genotoxicity using this genomic biomarker in TK6cells.
遗传毒性测试是化学物质评估的关键组成部分。在遗传毒理学中采用综合方法，包括纳入基因表达数据以确定参与反应的DNA损伤应答途径，正变得越来越普遍。在先前发表于《环境与分子突变》的相关论文中，Li等人（2015年）[6]制定了一种剂量优化方案，该方案基于在培养的人淋巴母细胞TK6中使用定量实时PCR评估几个特征明确的应激反应基因的表达变化。这种优化方法应用于对暴露于14种遗传毒性或14种非遗传毒性物质之一的TK6细胞的分析，在暴露后4小时取样。然后使用基于微阵列的转录组分析，采用最近收缩质心法开发遗传毒性分类器。确定了一组65个基因，这些基因可以准确地将毒物分类为遗传毒性或非遗传毒性。在Buick等人（2015年）[1]的研究中，评估了该生物标志物对需要代谢激活的化学物质的效用。在这项研究中，将TK6细胞在大鼠肝脏S9存在的情况下暴露于四种化学物质（两种需要代谢激活的遗传毒性物质和两种非遗传毒性化学物质）的递增剂量下，以证明S9不会损害使用该基因组生物标志物在TK6细胞中对遗传毒性进行分类的能力。
