Please use this identifier to cite or link to this item: http://hdl.handle.net/11455/40410
標題: Disturbed mitotic progression and genome segregation are involved in cell transformation mediated by nano-TiO2 long-term exposure
作者: Huang, S.
闕斌如
Chueh, P.J.
Lin, Y.W.
Shih, T.S.
Chuang, S.M.
莊秀美
關鍵字: Nano-particles
Aneuploidy
Cytotoxicity
Genotoxicity
TiO2
PLK1
ultrafine titanium-dioxide
polo-like kinases
oxidative stress
lung-cancer
alveolar macrophages
inhaled particles
epithelial-cells
mammalian-cells
surface-area
carbon-black
期刊/報告no:: Toxicology and Applied Pharmacology, Volume 241, Issue 2, Page(s) 182-194.
摘要: Titanium dioxide (TiO2) nano-particles (<100 nm in diameter) have been of interest in a wide range of applications, such as in cosmetics and pharmaceuticals because of their low toxicity. However recent Studies, have shown that TiO2 nano-particles (nano-TiO2) induce cytotoxicity and genotoxicity in various lines of Cultured cells as well as tumorigenesis in animal models. The biological roles of nano-TiO2 are shown to be controversial and no comprehensive study paradigm has been developed to investigate their molecular mechanisms. In this study, we showed that short-term exposure to nano-TiO2 enhanced cell proliferation, survival, ERK signaling activation and ROS production in Cultured fibroblast cells. Moreover, long-term exposure to nano-TiO2 not only increased cell Survival and growth on soft agar but also the numbers of multinucleated cells and micronucleus (MN) as suggested in confocal Microscopy analysis. Cell cycle phase analysis showed G2/M delay and slower cell division in long-term exposed cells. Most importantly, long-term TiO2 exposure remarkably affected mitotic progression at anaphase and telophase leading to aberrant multipolar spindles and chromatin alignment/segregation. Moreover, PLK1 was demonstrated as the target for nano-TiO2 in the regulation of mitotic progression and exit. Notably, a higher fraction of sub-G1 phase population appeared in TiO2-exposed cells after releasing from G2/M synchronization. Our results demonstrate that long-term exposure to nano-TiO2 disturbs cell cycle progression and duplicated genome segregation, leading to chromosomal instability and cell transformation. (C) 2009 Elsevier Inc. All rights reserved.
URI: http://hdl.handle.net/11455/40410
ISSN: 0041-008X
文章連結: http://dx.doi.org/10.1016/j.taap.2009.08.013
Appears in Collections:生物醫學研究所

文件中的檔案:

取得全文請前往華藝線上圖書館



Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.