title: The role of the tumor suppressor p53 pathway in the cellular DNA damage response to zinc oxide nanoparticles.
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.
authors.affiliation: School of Materials Science and Engineering, Nanyang Technological University, Singapore 639798, Singapore.
authors.forename: Kee Woei
authors.initials: KW
authors.lastname: Ng
authors.forename: Stella P K
authors.initials: SP
authors.lastname: Khoo
authors.forename: Boon Chin
authors.initials: BC
authors.lastname: Heng
authors.forename: Magdiel I
authors.initials: MI
authors.lastname: Setyawati
authors.forename: Eng Chok
authors.initials: EC
authors.lastname: Tan
authors.forename: Xinxin
authors.initials: X
authors.lastname: Zhao
authors.forename: Sijing
authors.initials: S
authors.lastname: Xiong
authors.forename: Wanru
authors.initials: W
authors.lastname: Fang
authors.forename: David T
authors.initials: DT
authors.lastname: Leong
authors.forename: Joachim S C
authors.initials: JS
authors.lastname: Loo
mesh_terms: D000818:Animals; D016923:Cell Death / Q000187:drug effects; D002460:Cell Line; D004249:DNA Damage; D006801:Humans; D051379:Mice; D008954:Models, Biological; D009153:Mutagens / Q000633:toxicity; D053758:Nanoparticles / Q000633:toxicity* / Q000648:ultrastructure; D015398:Signal Transduction / Q000187:drug effects*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D015034:Zinc Oxide / Q000633:toxicity*
chemical_list: D009153:Mutagens; D016159:Tumor Suppressor Protein p53; D015034:Zinc Oxide