NanoScience Technology Center, University of Central Florida, Orlando, Florida 32826, United States.
Anal Chem. 2013 Apr 16;85(8):4107-12. doi: 10.1021/ac400242w. Epub 2013 Apr 5.
This paper describes the use of a single cell array based assay for genotoxicity study of nanomaterials using normal human fetal fibroblast cells obtained from two-dimensional (2D) monolayer cultures and three-dimensional (3D) microtissue. After being exposed to a suspension of nanomaterials, cells are attached onto microfabricated patches with proper modification through electrostatic attraction and embedded in hydrogel. The damaged DNAs diffuse in gel matrix and form observable halo structures, where the level of DNA damage is quantified from the dimensions of core and halo. A concentration dependent genotoxicity has been found in nanomaterials. Compared to the traditional cytotoxicity (live/dead) assay, the genotoxicity results from the single cell array based assay are more robust and sensitive at the same exposure concentration, indicating that nanomaterials cause significant DNA damage without detectable cytotoxicity. In addition, cells from 3D microtissues are less damaged than 2D culture due to different cell microenvironments.
本文描述了一种基于单细胞阵列的分析方法,用于研究纳米材料的遗传毒性,所使用的细胞来自二维(2D)单层培养和三维(3D)微组织的正常人类胎儿成纤维细胞。在将纳米材料混悬液暴露于细胞后,细胞通过静电吸引附着在经过适当修饰的微加工片上,并嵌入水凝胶中。受损的 DNA 在凝胶基质中扩散,形成可观察到的晕圈结构,其中核心和晕圈的尺寸定量了 DNA 损伤的程度。在纳米材料中发现了浓度依赖性的遗传毒性。与传统的细胞毒性(死活)测定相比,单细胞阵列分析方法的遗传毒性结果在相同暴露浓度下更稳健和敏感,表明纳米材料在没有可检测细胞毒性的情况下引起了显著的 DNA 损伤。此外,由于不同的细胞微环境,来自 3D 微组织的细胞比 2D 培养的细胞受损程度更小。