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暴露于纳米银的人胃肠道上皮Caco2细胞中全局基因表达谱的改变

Altered global gene expression profiles in human gastrointestinal epithelial Caco2 cells exposed to nanosilver.

作者信息

Sahu Saura C

机构信息

Division of Toxicology, Office of Applied Research and Safety Assessment, Center for Food Safety and Applied Nutrition, U. S. Food and Drug Administration, Laurel, MD 20708, USA.

出版信息

Toxicol Rep. 2016 Jan 22;3:262-268. doi: 10.1016/j.toxrep.2016.01.012. eCollection 2016.

Abstract

Extensive consumer exposure to food- and cosmetics-related consumer products containing nanosilver is of public safety concern. Therefore, there is a need for suitable models and sensitive predictive rapid screening methods to assess their toxicity. Toxicogenomic profile showing subtle changes in gene expressions following nanosilver exposure is a sensitive toxicological endpoint for this purpose. We evaluated the Caco2 cells and global gene expression profiles as tools for predictive rapid toxicity screening of nanosilver. We evaluated and compared the gene expression profiles of Caco-2 cells exposed to 20 nm and 50 nm nanosilver at a concentration 2.5 μg/ml. The global gene expression analysis of Caco2 cells exposed to 20 nm nanosilver showed that a total of 93 genes were altered at 4 h exposure, out of which 90 genes were up-regulated and 3 genes were down-regulated. The 24 h exposure of 20 nm silver altered 15 genes in Caco2 cells, out of which 14 were up-regulated and one was down-regulated. The most pronounced changes in gene expression were detected at 4 h. The greater size (50 nm) nanosilver at 4 h exposure altered more genes by more different pathways than the smaller (20 nm) one. Metallothioneins and heat shock proteins were highly up-regulated as a result of exposure to both the nanosilvers. The cellular pathways affected by the nanosilver exposure is likely to lead to increased toxicity. The results of our study presented here suggest that the toxicogenomic characterization of Caco2 cells is a valuable tool for assessing toxicity of nanomaterials such as nanosilver.

摘要

消费者广泛接触含有纳米银的食品和化妆品相关消费品引发了公众安全担忧。因此,需要合适的模型和灵敏的预测性快速筛选方法来评估其毒性。纳米银暴露后基因表达出现细微变化的毒理基因组特征是用于此目的的一个灵敏毒理学终点。我们评估了Caco2细胞和全基因组表达谱作为纳米银预测性快速毒性筛选工具的情况。我们评估并比较了暴露于浓度为2.5μg/ml的20nm和50nm纳米银的Caco-2细胞的基因表达谱。对暴露于20nm纳米银的Caco2细胞进行的全基因组表达分析表明,暴露4小时时有总共93个基因发生改变,其中90个基因上调,3个基因下调。20nm银暴露24小时使Caco2细胞中的15个基因发生改变,其中14个上调,1个下调。在4小时时检测到基因表达变化最为明显。与较小尺寸(20nm)的纳米银相比,较大尺寸(50nm)的纳米银在暴露4小时时通过更多不同途径改变了更多基因。暴露于两种纳米银均导致金属硫蛋白和热休克蛋白高度上调。纳米银暴露所影响的细胞途径可能会导致毒性增加。我们在此呈现的研究结果表明,Caco2细胞的毒理基因组特征是评估纳米银等纳米材料毒性的一种有价值的工具。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9862/5615829/8766e2c725f9/gr1.jpg

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