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Cytoxic and Genotoxic Effects of Manufactured Nanoparticles on Stem Cells

人造纳米粒子对干细胞的细胞毒性和基因毒性作用

基本信息

批准号：
8600773
负责人：
Yiling Hong
金额：
$ 23.27万
依托单位：
WESTERN UNIVERSITY OF HEALTH SCIENCES
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-09-01 至 2015-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8600773
关键词：
Cytoxic Genotoxic Effects Manufactured Nanoparticles

项目摘要

Project Summary The use of NPs in commercially available products is rapidly increasing. As their use becomes more widespread, human exposure will consequently increase. Due to NPs unique properties, the potential hazards of NPs are only now being identified. There is a growing need for systematic toxicity studies especially to the very special cell type-stem cells. However, information is very limited regarding how stem cells respond to NPs. Our previous studies indicated the carbon nanotube and nanosilver particles can induce a DNA damage response in mouse embryonic stem cells. Stem cells are a unique cell population with the ability to undergo both self-renewal and differentiation. Adult stem cells constantly provide new cell lineages in our body. Increasing amounts of evidence suggest that stem cells may be the sources of mutant cells that give rise to cancerous tumors and maintain tumor growth. The systemic and detailed characterization of both cytotoxic and genotoxic Microsoft Office Word 2007.lnk effects of manufactured NP exposure to both embryonic stem cells, induced stem cells (iPS) and adult stem cells will thoroughly evaluate the health and safety effects of NPs and greatly enhance consumer confidence. In this proposal, we will be initially using four NP types that are, or will be, prominently used in commercially available products: carbon NPs (car wax, fuel lines, cosmetics), silver NPs (antimicrobial wound dressings, odor-reducing socks), titanium dioxide NPs (sunscreens, paints), and zinc oxide NPs (sunscreens). It is vital to have confidence in the suppliers of these NPs. We are fortunate to have strong collaborative links with NP manufacturing experts within the University of Dayton and other institutes who will provide these particles. We propose the following specific aims: Aim 1. Characterize the impact of these selected manufactured nanoparticles to stem cells self renewal and differentiation potentials. Mouse embryonic stem cells, induced human pluripotent stem cells (ihPS), and human mesenchymal stem cells will be used for this study. Aim2. Investigate p53 activation as a possible molecular marker to study the stem cell cytotoxic and genotoxic response to these selected manufactured nanoparticles. Aim3. Using an endogenous molecular marker adenine phosphoribosyltransferase (Aprt) as a reporter to study genotoxic effect to these selected nanoparticles.

项目摘要纳米粒子在市售产品中的使用正在迅速增加。使用雇佣军如果辐射范围越来越广，人类接触的辐射也会随之增加。由于NP 由于其独特的性质，纳米颗粒的潜在危害现在才被发现。有一个越来越需要系统的毒性研究，特别是对非常特殊的细胞类型-干细胞细胞然而，关于干细胞如何响应NP的信息非常有限。我们以前的研究表明，碳纳米管和纳米银颗粒可以诱导DNA 小鼠胚胎干细胞的损伤反应。干细胞是一个独特的细胞群体具有自我更新和分化的能力。成体干细胞为我们的身体提供新的细胞谱系。越来越多的证据表明，细胞可能是突变细胞的来源，这些突变细胞引起癌性肿瘤，肿瘤生长细胞毒性和遗传毒性的系统和详细表征 Microsoft Office Word 2007.lnk暴露于胚胎干细胞的人造NP的影响干细胞，诱导干细胞（iPS）和成体干细胞将彻底评估健康和纳米粒子的安全效果，大大增强了消费者的信心。在这份提案中，我们将最初使用四种NP类型，这些NP类型是或将主要用于商业上可获得的产品：碳纳米颗粒（汽车蜡，燃料线，化妆品），银纳米颗粒（抗菌伤口敷料、除臭袜）、二氧化钛纳米颗粒（防晒霜、油漆）和氧化锌 NPs（防晒霜）。对这些NP的供应商有信心至关重要。我们幸运的是，我们与NP制造专家建立了强大的合作关系，代顿大学和其他研究所谁将提供这些粒子。我们建议具体目标如下：目标1。表征这些选定的制造纳米颗粒对股骨柄的影响细胞自我更新和分化潜能。小鼠胚胎干细胞，诱导的人多能干细胞（ihPS）和人间充质干细胞将用于本研究。目标2。探讨p53活化作为研究干细胞的可能分子标志物细胞毒性和遗传毒性反应。目标3。利用内源性分子标记腺嘌呤磷酸核糖转移酶（Aprt）作为报告基因，研究这些选定的纳米颗粒的遗传毒性效应。