title: Toxicogenomic analysis of the particle dose- and size-response relationship of silica particles-induced toxicity in mice.
abstract: 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.
authors.affiliation: Pharmaceutical Informatics Institute, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, People's Republic of China.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Lu
authors.forename: Tingting
authors.initials: T
authors.lastname: Jin
authors.forename: Yachao
authors.initials: Y
authors.lastname: Jin
authors.forename: Leihong
authors.initials: L
authors.lastname: Wu
authors.forename: Bin
authors.initials: B
authors.lastname: Hu
authors.forename: Yu
authors.initials: Y
authors.lastname: Tian
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Fan
mesh_terms: D000818:Animals; D016000:Cluster Analysis; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D020556:Neutrophil Infiltration / Q000187:drug effects / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D010316:Particle Size; D025341:Principal Component Analysis; D060066:Protein Interaction Maps / Q000187:drug effects / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D015203:Reproducibility of Results; D012822:Silicon Dioxide / Q000737:chemistry* / Q000633:toxicity*; D014018:Tissue Distribution / Q000187:drug effects; D043922:Toxicogenetics / Q000379:methods*
chemical_list: D012822:Silicon Dioxide