title: Nano-sized titanium dioxide-induced splenic toxicity: a biological pathway explored using microarray technology.
abstract: Titanium dioxide nanoparticles (TiO2 NPs) have been widely used in various areas, and its potential toxicity has gained wide attention. However, the molecular mechanisms of multiple genes working together in the TiO2 NP-induced splenic injury are not well understood. In the present study, 2.5, 5, or 10mg/kg body weight TiO2 NPs were administered to the mice by intragastric administration for 90 consecutive days, their immune capacity in the spleen as well as the gene-expressed characteristics in the mouse damaged spleen were investigated using microarray assay. The findings showed that with increased dose, TiO2 NP exposure resulted in the increases of spleen indices, immune dysfunction, and severe macrophage infiltration as well as apoptosis in the spleen. Importantly, microarray data showed significant alterations in the expressions of 1041 genes involved in immune/inflammatory responses, apoptosis, oxidative stress, stress responses, metabolic processes, ion transport, signal transduction, cell proliferation/division, cytoskeleton and translation in the 10 mg/kg TiO2 NP-exposed spleen. Specifically, Cyp2e1, Sod3, Mt1, Mt2, Atf4, Chac1, H2-k1, Cxcl13, Ccl24, Cd14, Lbp, Cd80, Cd86, Cd28, Il7r, Il12a, Cfd, and Fcnb may be potential biomarkers of spleen toxicity following exposure to TiO2 NPs.
authors: Medical College of Soochow University, Suzhou 215123, China.
authors: Lei
authors: L
authors: Sheng
authors: Library of Soochow University, Suzhou 215123, China.
authors: Ling
authors: L
authors: Wang
authors: Medical College of Soochow University, Suzhou 215123, China.
authors: Xuezi
authors: X
authors: Sang
authors: Medical College of Soochow University, Suzhou 215123, China.
authors: Xiaoyang
authors: X
authors: Zhao
authors: Medical College of Soochow University, Suzhou 215123, China.
authors: Jie
authors: J
authors: Hong
authors: Medical College of Soochow University, Suzhou 215123, China.
authors: Shen
authors: S
authors: Cheng
authors: Medical College of Soochow University, Suzhou 215123, China.
authors: Xiaohong
authors: X
authors: Yu
authors: Medical College of Soochow University, Suzhou 215123, China.
authors: Dong
authors: D
authors: Liu
authors: Medical College of Soochow University, Suzhou 215123, China.
authors: Bingqing
authors: B
authors: Xu
authors: Medical College of Soochow University, Suzhou 215123, China.
authors: Renping
authors: R
authors: Hu
authors: Medical College of Soochow University, Suzhou 215123, China.
authors: Qingqing
authors: Q
authors: Sun
authors: Medical College of Soochow University, Suzhou 215123, China.
authors: Jie
authors: J
authors: Cheng
authors: Medical College of Soochow University, Suzhou 215123, China.
authors: Zhe
authors: Z
authors: Cheng
authors: Medical College of Soochow University, Suzhou 215123, China.
authors: Suxin
authors: S
authors: Gui
authors: Medical College of Soochow University, Suzhou 215123, China. Electronic address: Hongfsh_cn@sina.com.
authors: Fashui
authors: F
authors: Hong
mesh_terms: D000818:Animals; D001772:Blood Cell Count; D005260:Female; D020869:Gene Expression Profiling; D008813:Mice, Inbred ICR; D046228:Microarray Analysis; D046529:Microscopy, Electron, Transmission; D053758:Nanoparticles / Q000633:toxicity*; D009929:Organ Size / Q000187:drug effects; D012313:RNA / Q000235:genetics / Q000378:metabolism; D013154:Spleen / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D014025:Titanium / Q000378:metabolism / Q000493:pharmacokinetics / Q000633:toxicity*
chemical_list: C009495:titanium dioxide; D012313:RNA; D014025:Titanium
keywords: Gene-expressed profile; Spleen injury; Splenic dysfunction; Titanium dioxide nanoparticles