title: Molecular mechanisms of nanosized titanium dioxide-induced pulmonary injury in mice.
abstract: The pulmonary damage induced by nanosized titanium dioxide (nano-TiO2) is of great concern, but the mechanism of how this damage may be incurred has yet to be elucidated. Here, we examined how multiple genes may be affected by nano-TiO2 exposure to contribute to the observed damage. The results suggest that long-term exposure to nano-TiO2 led to significant increases in inflammatory cells, and levels of lactate dehydrogenase, alkaline phosphate, and total protein, and promoted production of reactive oxygen species and peroxidation of lipid, protein and DNA in mouse lung tissue. We also observed nano-TiO2 deposition in lung tissue via light and confocal Raman microscopy, which in turn led to severe pulmonary inflammation and pneumonocytic apoptosis in mice. Specifically, microarray analysis showed significant alterations in the expression of 847 genes in the nano-TiO2-exposed lung tissues. Of 521 genes with known functions, 361 were up-regulated and 160 down-regulated, which were associated with the immune/inflammatory responses, apoptosis, oxidative stress, the cell cycle, stress responses, cell proliferation, the cytoskeleton, signal transduction, and metabolic processes. Therefore, the application of nano-TiO2 should be carried out cautiously, especially in humans.
authors: Medical College of Soochow University, Suzhou, China.
authors: Bing
authors: B
authors: Li
authors: Yuguan
authors: Y
authors: Ze
authors: Qingqing
authors: Q
authors: Sun
authors: Ting
authors: T
authors: Zhang
authors: Xuezi
authors: X
authors: Sang
authors: Yaling
authors: Y
authors: Cui
authors: Xiaochun
authors: X
authors: Wang
authors: Suxin
authors: S
authors: Gui
authors: Danlin
authors: D
authors: Tan
authors: Min
authors: M
authors: Zhu
authors: Xiaoyang
authors: X
authors: Zhao
authors: Lei
authors: L
authors: Sheng
authors: Ling
authors: L
authors: Wang
authors: Fashui
authors: F
authors: Hong
authors: Meng
authors: M
authors: Tang
mesh_terms: D000818:Animals; D001992:Bronchoalveolar Lavage Fluid; D015536:Down-Regulation; D020869:Gene Expression Profiling; D015227:Lipid Peroxidation; D008168:Lung / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D053768:Metal Nanoparticles / Q000633:toxicity*; D051379:Mice; D018613:Microscopy, Confocal; D020411:Oligonucleotide Array Sequence Analysis; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D014025:Titanium / Q000633:toxicity*; D015854:Up-Regulation
chemical_list: D017382:Reactive Oxygen Species; C009495:titanium dioxide; D014025:Titanium