Dipartimento di Medicina Clinica e Sperimentale, Unità di Biologia applicata e Genetica, Università di Pisa, Via A. Volta 4, 56126 Pisa, Italy.
Mutagenesis. 2013 Mar;28(2):171-80. doi: 10.1093/mutage/ges068. Epub 2013 Jan 15.
Although amorphous silica is used in food products, cosmetics and paints and as vector for drug delivery, data on its potential health hazard are limited. The aim of this study was to investigate the cytotoxic and genotoxic potential of silica particles of different sizes (250 and 500nm) and structures (dense and mesoporous). Dense silica (DS) spheres were prepared by sol-gel synthesis, mesoporous silica particles (MCM-41) were prepared using hexadecyltrimethyl ammonium bromide as a structure-directing agent and tetraethylorthosilicate as silica source. Particles were accurately characterised by dynamic light scattering, nitrogen adsorption, X-ray diffraction and field emission scanning electron microscopy. Murine macrophages (RAW264.7) and human epithelial lung (A549) cell lines were selected for investigation. Genotoxicity was evaluated by Comet assay and micronucleus test. Cytotoxicity was tested by the trypan blue method. Cells were treated with 0, 5, 10, 20, 40 and 80 µg/cm(2) of different silica powders for 4 and 24 h. The intracellular localisation of silica was investigated by transmission electron microscopy. Amorphous particles penetrated into the cells, being compartmentalised within endocytic vacuoles. DS and MCM-41 particles induced cytotoxic and genotoxic effects in A549 and RAW264.7 although to different extent in the two cell lines. A549 were resistant in terms of cell viability, but showed a generalised induction of DNA strand breaks. RAW264.7 were susceptible to amorphous silica exposure, exhibiting both cytotoxic and genotoxic responses as DNA strand breaks and chromosomal alterations. The cytotoxic response of RAW264.7 was particularly relevant after MCM-41 exposure. The genotoxicity of amorphous silica highlights the need for a proper assessment of its potential hazard for human health.
虽然无定形二氧化硅被用于食品、化妆品和涂料中，并作为药物输送载体，但关于其潜在健康危害的数据有限。本研究旨在研究不同尺寸（250 和 500nm）和结构（致密和介孔）的二氧化硅颗粒的细胞毒性和遗传毒性潜力。致密二氧化硅（DS）球体通过溶胶-凝胶合成制备，介孔二氧化硅颗粒（MCM-41）使用十六烷基三甲基溴化铵作为结构导向剂和四乙氧基硅烷作为硅源制备。通过动态光散射、氮气吸附、X 射线衍射和场发射扫描电子显微镜对颗粒进行了准确的表征。选择小鼠巨噬细胞（RAW264.7）和人上皮肺（A549）细胞系进行研究。通过彗星试验和微核试验评估遗传毒性。通过台盼蓝法测试细胞毒性。用 0、5、10、20、40 和 80µg/cm(2)的不同二氧化硅粉末处理细胞 4 和 24 小时。通过透射电子显微镜研究二氧化硅在细胞内的定位。无定形颗粒穿透细胞，被区室化在胞内体中。DS 和 MCM-41 颗粒在 A549 和 RAW264.7 中诱导细胞毒性和遗传毒性效应，尽管在两种细胞系中程度不同。A549 在细胞活力方面具有抗性，但表现出 DNA 链断裂的普遍诱导。RAW264.7 对无定形二氧化硅暴露敏感，表现出 DNA 链断裂和染色体改变的细胞毒性和遗传毒性反应。RAW264.7 的细胞毒性反应在 MCM-41 暴露后尤为明显。无定形二氧化硅的遗传毒性突出表明需要对其对人类健康的潜在危害进行适当评估。
