A preliminary assessment of levels of bioavailable anthropogenic platinum-group, lanthanide and high field strength metals in human tissue and DNA.

对人体组织和 DNA 中生物可利用的人为铂族、镧系元素和高场强金属水平的初步评估。

• 批准号: NE/E008062/1
• 负责人: David Pearson
• 金额: $ 7.78万
• 依托单位: Newcastle University
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2008
• 资助国家: 英国
• 起止时间: 2008 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=NE%2FE008062%2F1
• 关键词: preliminary; assessment; levels; bioavailable; anthropogenic

The addition of lead substitutes to automotive fuel and the introduction of catalytic converters have led to the appearance of several other, normally rare metals, in exhaust emissions. Over 95% of all cars now manufactured have metal-based two or three-way catalytic converters and emissions from these systems is leading to a well documented, dramatic increase in the concentration of platinum in roadside and tunnel dusts. Little information is available for some of the other rare metals such as cerium, hafnium and zirconium, which can be present in very much higher abundances than Pt in the wash coats of converters, but it is likely that they are accumulating too, probably in much greater abundances. These metals are emitted as ultra-fine reactive particles, and so are readily absorbed when inhaled and consequently are more likely to produce toxicological effects. A chance discovery that at least one of these metals, hafnium, may become incorporated into the primary genetic material (DNA) of some individuals implies that even metals which are usually innocuous can become biologically active if absorbed by the lung in this way. More importantly, this incorporation into DNA implies that they might increase the risk of lung or other cancers by altering or damaging DNA replication. Some of the metals in question (cerium and hafnium) have isotopic compositions that vary in nature and it may be possible to specifically identify the source and sink of these elements in the environment and in the human body through characteristic isotopic compositions that will 'fingerprint' their origin. To properly evaluate the risk to human health through accumulation of these metals in the environment we need to instigate a research programme to define basic information such as:- Is there evidence for accumulation of anthropogenic cerium, hafnium and zirconium consistent with the increase in some platinum group elements? What are the main environmental sources and pathways of these metals into human receptors and what are the most bioavailable forms? To what extent do these levels vary between individuals? To what extent can we distinguish sources using isotope ratio tracing? What are typical baseline levels of these metals, in human organs such as the lungs and the liver, in human blood and in DNA extracts? To what extent do the metals become mobilised and biologically active by measurement of the levels bound to DNA and certain proteins We have assembled a diverse team of scientists with environmental, biomedical, clinical and toxicological expertise that offer a very fortuitous combination of the latest analytical and extraction technology plus access to human tissue and blood samples. This cross-disciplinary team, together with a post-doctoral scientist, will be well pace to answer the above questions and hence provide preliminary data on which to base future studies and risk assessments for human health.

在汽车燃料中添加铅替代品和采用催化转化器，导致废气排放中出现了其他几种通常是稀有金属。现在生产的所有汽车中有95%以上都装有金属基二元或三元催化转化器，这些系统的排放导致路边和隧道灰尘中铂浓度的显著增加。关于铈、铪和锆等其他一些稀有金属的信息很少，这些金属在转炉洗涂层中的丰度可能比铂高得多，但它们可能也在积累，而且可能以更高的丰度积累。这些金属以超细活性颗粒的形式排放，因此在吸入时很容易被吸收，因此更有可能产生毒理学效应。一个偶然的发现，这些金属中至少有一种，铪，可能会被纳入一些人的主要遗传物质（DNA），这意味着即使是通常无害的金属，如果以这种方式被肺部吸收，也会变得具有生物活性。更重要的是，这种结合到DNA中意味着它们可能会通过改变或破坏DNA复制来增加肺癌或其他癌症的风险。某些金属（铈和铪）的同位素组成在性质上各不相同，通过特征同位素组成，可以明确识别这些元素在环境和人体中的来源和汇，这将“指纹”它们的来源。为了正确评估这些金属在环境中积累对人类健康的风险，我们需要发起一项研究方案，以确定基本信息，如：-是否有证据表明人为铈、铪和锆的积累与某些铂族元素的增加一致？这些金属进入人体受体的主要环境来源和途径是什么？生物利用度最高的形式是什么？这些水平在多大程度上因人而异？同位素比示踪能在多大程度上区分放射源？这些金属在人体器官（如肺和肝）、人体血液和DNA提取物中的典型基线水平是多少？通过测量与DNA和某些蛋白质结合的水平，金属在多大程度上被动员和具有生物活性我们组建了一支由环境、生物医学、临床和毒理学专业知识的多元化科学家团队，提供最新分析和提取技术以及人体组织和血液样本的非常偶然的组合。这个跨学科小组将与一名博士后科学家一起，迅速回答上述问题，从而提供初步数据，作为今后研究和人类健康风险评估的基础。