Please use this identifier to cite or link to this item: http://hdl.handle.net/11455/95489
標題: Disturbed mitotic progression and genome segregation are involved in cell transformation mediated by nano-TiO2 long-term exposure
作者: Huang, Shing
Chueh, Pin Ju
Lin, Yun-Wei
Shih, Tung-Sheng
Chuang, Show-Mei
莊秀美
關鍵字: Animals
Cell Cycle Proteins
Cell Proliferation
Cell Survival
Cell Transformation, Neoplastic
Cytotoxins
DNA Damage
Dose-Response Relationship, Drug
Drug Administration Schedule
Extracellular Signal-Regulated MAP Kinases
Mice
Mitosis
NIH 3T3 Cells
Nanoparticles
Protein-Serine-Threonine Kinases
Proto-Oncogene Proteins
Reactive Oxygen Species
Titanium
Chromosome Segregation
出版社: TOXICOLOGY AND APPLIED PHARMACOLOGY
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.
URI: http://hdl.handle.net/11455/95489
文章連結: https://www.sciencedirect.com/science/article/pii/S0041008X09003494?via%3Dihub
Appears in Collections:生物醫學研究所

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