Toxicogenomic analysis of the particle dose- and size-response relationship of silica particles-induced toxicity in mice

• Published in: Nanotechnology Vol. 24; no. 1; pp. 015106 - 1-12
• Main Authors: Lu, Xiaoyan, Jin, Tingting, Jin, Yachao, Wu, Leihong, Hu, Bin, Tian, Yu, Fan, Xiaohui
• Format: Journal Article
• Language: English
• Published: Bristol IOP Publishing 11.01.2013; Institute of Physics
• Subjects: Animals; Biological and medical sciences; Biotechnology; Cluster Analysis; Fundamental and applied biological sciences. Psychology; Gene Expression Profiling; Gene Expression Regulation - drug effects; Liver - drug effects; Liver - metabolism; Liver - pathology; Male; Methods. Procedures. Technologies; Mice; Mice, Inbred BALB C; Neutrophil Infiltration - drug effects; Neutrophil Infiltration - genetics; Oligonucleotide Array Sequence Analysis; Others; Particle Size; Principal Component Analysis; Protein Interaction Maps - drug effects; Protein Interaction Maps - genetics; Real-Time Polymerase Chain Reaction; Reproducibility of Results; Silicon Dioxide - chemistry; Silicon Dioxide - toxicity; Tissue Distribution - drug effects; Toxicogenetics - methods; Various methods and equipments; In vivo; Particle size; Toxicity; Imaging; Stress effects; Surface area; Dose; Silica
• ISSN: 0957-4484; 1361-6528
• DOI: 10.1088/0957-4484/24/1/015106

This study investigated the relationship between particle size and toxicity of silica particles (SP) with diameters of 30, 70, and 300 nm, which is essential to the safe design and application of SP. Data obtained from histopathological examinations suggested that SP of these sizes can all induce acute inflammation in the liver. In vivo imaging showed that intravenously administrated SP are mainly present in the liver, spleen and intestinal tract. Interestingly, in gene expression analysis, the cellular response pathways activated in the liver are predominantly conserved independently of particle dose when the same size SP are administered or are conserved independently of particle size, surface area and particle number when nano- or submicro-sized SP are administered at their toxic doses. Meanwhile, integrated analysis of transcriptomics, previous metabonomics and conventional toxicological results support the view that SP can result in inflammatory and oxidative stress, generate mitochondrial dysfunction, and eventually cause hepatocyte necrosis by neutrophil-mediated liver injury.