Please use this identifier to cite or link to this item: https://doi.org/10.1016/j.biomaterials.2011.07.036
Title: The role of the tumor suppressor p53 pathway in the cellular DNA damage response to zinc oxide nanoparticles
Authors: Ng, K.W.
Khoo, S.P.K.
Heng, B.C.
Setyawati, M.I.
Tan, E.C.
Zhao, X.
Xiong, S.
Fang, W. 
Leong, D.T. 
Loo, J.S.C.
Keywords: DNA damage
Genotoxicology
Nanoparticles
Nanotoxicology
P53
Zinc oxide
Issue Date: Nov-2011
Source: Ng, K.W.,Khoo, S.P.K.,Heng, B.C.,Setyawati, M.I.,Tan, E.C.,Zhao, X.,Xiong, S.,Fang, W.,Leong, D.T.,Loo, J.S.C. (2011-11). The role of the tumor suppressor p53 pathway in the cellular DNA damage response to zinc oxide nanoparticles. Biomaterials 32 (32) : 8218-8225. ScholarBank@NUS Repository. https://doi.org/10.1016/j.biomaterials.2011.07.036
Abstract: In this paper, we explored how ZnO nanoparticles cross-interact with a critical tumor suppressive pathway centered around p53, which is one of the most important known tumor suppressors that protects cells from developing cancer phenotypes through its control over major pathways like apoptosis, senescence and cell cycle progression. We showed that the p53 pathway was activated in BJ cells (skin fibroblasts) upon ZnO nanoparticles treatment with a concomitant decrease in cell numbers. This suggests that cellular responses like apoptosis in the presence of ZnO nanoparticles require p53 as the molecular master switch towards programmed cell death. This also suggests that in cells without robust p53, protective response can be tipped towards carcinogenesis when stimulated by DNA damage inducing agents like ZnO nanoparticles. We observed this precarious tendency in the same BJ cells with p53 knocked down using endogeneous expressing shRNA. These p53 knocked down BJ cells became more resistant to ZnO nanoparticles induced cell death and increased cell progression. Collectively, our results suggest that cellular response towards specific nanoparticle induced cell toxicity and carcinogenesis is not only dependent on specific nanoparticle properties but also (perhaps more importantly) the endogenous genetic, transcriptomic and proteomic landscape of the target cells. © 2011 Elsevier Ltd.
Source Title: Biomaterials
URI: http://scholarbank.nus.edu.sg/handle/10635/64718
ISSN: 01429612
DOI: 10.1016/j.biomaterials.2011.07.036
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