TRANSLOCATION OF INHALED ULTRAFINE ELEMENTAL CARBON PARTICLS TO EXTRAPUL TISSUE

吸入的超细元素碳颗粒转移至超薄组织

• 批准号: 7359003
• 负责人: GUNTER OBERDORSTER
• 金额: $ 1.32万
• 依托单位: UNIVERSITY OF CALIF-LAWRNC LVRMR NAT LAB
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-01 至 2007-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7359003
• 关键词: TRANSLOCATION; INHALED; ULTRAFINE; ELEMENTAL; CARBON

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Ultrafine particles (particles 100 nm in diameter) are ubiquitous in the ambient air from anthropogenic and natural sources (e.g., internal combustion engine emissions, gas to particle conversions). The new field of nanotechnology in industrial and medical use adds an additional component. Inhalation of ultrafine particles is known to cause adverse effects in pulmonary and extrapulmonary tissues. Based on our earlier studies with ultrafine 13C elemental carbon particles we hypothesize that such particles can translocate from sites of deposition to extrapulmonary organs such as the liver and the brain. Due to the inherent problem of 13C background levels in tissues for assessing significant increases in added tissue carbon a more sensitive method is needed. We propose to generate ultrafine elemental carbon particles labeled with 14C to which rats will be exposed by inhalation, gavage and i.v. injection to these particles. The size of the ultrafine 14C particles ranges from ~10 nm to ~80 nm. Rats will be sacrificed at different timepoints after exposure and lungs, liver, heart, kidney, spleen and brain sections (olfactory; cerebrum; cerebellum) excised and prepared for 14C accelerator mass spectrometry. These studies are part of an EPA-funded Ultrafine Particle Center at Rochester. Studies performed by Center investigators focus on physico-chemical characterization of ambient UFP; epidemiological studies; controlled clinical studies; toxicological animal studies; and mechanistic in vitro studies. The proposed research in collaboration with LLNL will have great significance to elucidate the fate of inhaled ultrafine particles after their deposition in the respiratory tract. If significant amounts of ultrafine particles are translocated to sensitive sites such as the heart and the brain, it may explain both short-term and long-term effects of ambient particulate pollution.

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。超细颗粒（直径100纳米的颗粒）在人为和自然来源（例如，内燃机排放，气体到颗粒的转换）的环境空气中无处不在。纳米技术在工业和医疗领域的新应用增加了一个额外的组成部分。众所周知，吸入超细颗粒会对肺和肺外组织造成不良影响。根据我们早期对超细13C元素碳颗粒的研究，我们假设这些颗粒可以从沉积部位转移到肺外器官，如肝脏和大脑。由于组织中13C背景水平的固有问题，需要一种更敏感的方法来评估添加组织碳的显着增加。我们拟制备带有14C标记的超细单质碳颗粒，通过吸入、灌胃和静脉注射的方式使大鼠暴露于这些颗粒中。超细14C颗粒的粒径范围为~10 ~ ~80 nm。暴露后于不同时间点处死大鼠，切除肺、肝、心、肾、脾和脑（嗅觉、大脑、小脑）切片，制备14C加速器质谱分析。这些研究是美国环保署资助的罗切斯特超细颗粒中心的一部分。中心研究人员进行的研究侧重于环境UFP的物理化学特性；流行病学研究;对照临床研究；动物毒理学研究；以及体外机制研究。本次与LLNL的合作研究对于阐明吸入的超细颗粒在呼吸道沉积后的命运具有重要意义。如果大量的超细颗粒转移到心脏和大脑等敏感部位，这或许可以解释环境颗粒污染的短期和长期影响。