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首页> 外文学位 >Effect of the nano-bio interface on the genotoxicity of titanium dioxide nanoparticles and associated cellular responses.
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Effect of the nano-bio interface on the genotoxicity of titanium dioxide nanoparticles and associated cellular responses.

机译：纳米生物界面对二氧化钛纳米粒子的遗传毒性和相关细胞反应的影响。

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摘要

Several toxicological studies have shown that titanium dioxide nanoparticles (nano-TiO2), one of the most widely produced engineered nanoparticles, can induce genotoxicity; however, potential adverse health effects associated with their physicochemical properties are not fully understood. Proteins in a biological medium can adsorb to the surface of the nanoparticle resulting in the formation of a protein corona that can alter the physicochemical properties of the particle. Furthermore, the protein corona may impact the interaction between nanoparticles and cells, referred to as the nano-bio interface, effecting the uptake, distribution, and toxicity of the particles. Despite the potential influence of the composition of the biological medium on the physicochemical properties and genotoxicity of titanium dioxide nanoparticles, the majority of studies have not examined systematically the influence of medium composition on protein corona, genotoxicity, and cellular responses.;In this dissertation we tested the overall hypothesis that titanium dioxide nanoparticles in medium that produces the smallest agglomerates would be taken up into cells and induce genotoxicity, and that exposure would initiate the signaling of key mediators of a DNA damage and inflammation response. Three major findings were shown in this study: 1) Protein corona formation on the surface of nano-TiO2 can impact the nano-bio interface and change cellular interaction. 2) Smaller agglomerates of nano-TiO2 are taken up more by cells without inducing cell cycle arrest, thereby allowing induced DNA damage to be processed into micronuclei in BEAS-2B cells. 3) Nano-TiO 2 in medium that facilitates increased cellular interaction induces the upregulation of the ATM-Chk2 DNA damage response (similar to ionizing radiation) and NF-κB inflammation pathways.;Taken together, our research provides a systematic examination of the physicochemical properties, genotoxicity, and cellular responses induced by titanium dioxide nanoparticles. The impact of cell type and cell culture conditions must be considered when analyzing in vitro studies for a health risk assessment of engineered nanoparticles. Therefore, we conclude that there is limited ability to make a general prediction regarding the in vitro genotoxicity of titanium dioxide nanoparticles without understanding further the toxicological implications of the nano-bio interface.
机译：几项毒理学研究表明，二氧化钛纳米颗粒（nano-TiO2）是最广泛生产的工程化纳米颗粒之一，可诱导遗传毒性。然而，与其理化性质有关的潜在不良健康影响尚不完全清楚。生物介质中的蛋白质可以吸附到纳米颗粒的表面，从而导致蛋白质电晕的形成，从而可以改变颗粒的物理化学性质。此外，蛋白质电晕可能会影响纳米颗粒与细胞之间的相互作用（称为纳米生物界面），从而影响颗粒的吸收，分布和毒性。尽管生物介质的组成对二氧化钛纳米颗粒的理化性质和遗传毒性有潜在的影响，但大多数研究尚未系统地检查介质组成对蛋白质电晕，遗传毒性和细胞反应的影响。检验了整个假设，即产生最小团聚体的介质中的二氧化钛纳米颗粒将被细胞吸收并引起遗传毒性，而暴露会引发DNA损伤和炎症反应的关键介质的信号传导。这项研究显示了三个主要发现：1）纳米TiO2表面的蛋白质电晕形成会影响纳米生物界面并改变细胞相互作用。 2）较小的纳米TiO2团聚物在不引起细胞周期停滞的情况下被细胞吸收，从而使诱导的DNA损伤被加工为BEAS-2B细胞中的微核。 3）促进细胞相互作用增强的介质中的纳米TiO 2诱导了ATM-Chk2 DNA损伤反应（类似于电离辐射）和NF-κB炎症途径的上调。;综合起来，我们的研究提供了对理化作用的系统检查二氧化钛纳米颗粒诱导的性质，遗传毒性和细胞反应。在分析工程化纳米粒子的健康风险评估的体外研究时，必须考虑细胞类型和细胞培养条件的影响。因此，我们得出结论，在不进一步了解纳米生物界面的毒理学含义的情况下，对二氧化钛纳米粒子的体外遗传毒性做出一般性预测的能力有限。

著录项

  • 作者

    Prasad, Raju Yashaswi.;

  • 作者单位

    The University of North Carolina at Chapel Hill.;

  • 授予单位 The University of North Carolina at Chapel Hill.;
  • 学科 Health Sciences Toxicology.;Environmental Sciences.;Nanoscience.
  • 学位 Ph.D.
  • 年度 2013
  • 页码 181 p.
  • 总页数 181
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

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