Elucidating the potential interaction of manufactured nanoparticles with polycyclic aromatic hydrocarbons: An integrated toxicogenomics approach

阐明人造纳米粒子与多环芳烃的潜在相互作用：综合毒物基因组学方法

• 批准号: NE/L006782/1
• 负责人: Awadhesh Jha
• 金额: $ 72.25万
• 依托单位: Plymouth University
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2014
• 资助国家: 英国
• 起止时间: 2014 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=NE%2FL006782%2F1
• 关键词: Elucidating; potential; interaction; manufactured; nanoparticles

Particles in the range of 1-100 nanometers (a nanometer is one billionth of a meter) are termed nanoparticles and are widely present in the environment. But, man-made nanoparticles (i.e. engineered nanoparticles or ENPs) are of tremendous technological and economic interest. They have a wide range of potential applications in environmental remediation, medical and consumer products. The small sizes of ENPs give them special chemical properties, making them potentially reactive. These particles are being discharged, voluntary or involuntary, into the environment in common with other pollutants such as those present in diesel exhaust, oil leaks and spills, tobacco smokes. These chemicals are collectively known as polycyclic aromatic hydrocarbons (PAHs) and they have known detrimental effects on the health of humans and the natural biota, including induction of cancer. The reactive property of ENPs can potentially cause harm to humans and other life forms and in the environment, they can occur in all probable combinations with other pollutants such as PAHs. They can interact and behave in different ways, opposed to when they are present on their own in the environment. Their potential interactive effects are however unknown. Within the cells (the smallest unit of life), they can cause damage to biomolecules (e.g. membranes, proteins and DNA). In addition to direct interaction of ENPs and PAHs with biomolecules (e.g. DNA, cell membrane), the resultant damage could be through the formation of highly reactive molecules called free radicals which are involved in many pathological conditions, which we aim to measure using specific technique, the methodologies for which have not been properly developed. This is particularly so in cases where they are brought into contact with water under different conditions (e.g. salinity, acidity, oxygen level etc.) either alone or in combinations with other pollutants such as PAHs. We will be synthesise ENPs in our laboratory and will characterise them for their specific properties in various conditions, track their uptake by the mussels (alone or in combination with PAHs) and localise them in different tissues using analytical techniques where appropriate. Using two chemically different, widely used, environmentally relevant ENPs (i.e. C60 fullerenes and carbon nanotubes), the aim of the present proposal is to determine the potential effects of these ENPs either alone or in combinations with environmentally relevant PAHs. We will be using a range of biological measures, which will include damage to DNA or genes, the blueprint of life, and determine how either the single or group of genes behave in different conditions, which could lead to potential detrimental effects in different organs or tissues of marine mussels. We will vary the extent of damage produced, by altering the exposure conditions (chronically or acute) and will also determine the antioxidants levels to correlate the effects. The damaging effect of generated radicals on cell membranes will also be examined. We will use modelling techniques to incorporate individual biological responses to draw a bigger picture of potential effects. Using analytical techniques, we will determine the levels of ENPs and PAHs in seawater and the tissues of the organism and will correlate these levels with observed effects. Such an approach will help us to determine the potential risk to our health from these chemicals and will inform the regulators and the industries to take appropriate actions to safeguard the health of humans and the environment. We will use the generated information to explain the pathways of exposure to ENPs and PAHs and suggest ways to reduce any potential harm. This may also have application in the treatment of diseases such as cancer. We will share the information with the scientific community, industries, and all other stake holders.

1-100纳米(一纳米等于十亿分之一米)的颗粒被称为纳米颗粒，广泛存在于环境中。但是，人造纳米颗粒(即工程纳米颗粒或ENPs)具有巨大的技术和经济利益。它们在环境修复、医疗和消费产品中具有广泛的潜在应用。ENPs的小尺寸赋予了它们特殊的化学性质，使它们具有潜在的活性。这些颗粒物与柴油废气、漏油和泄漏、烟草烟雾等其他污染物一样，自愿或非自愿地排放到环境中。这些化学物质统称为多环芳烃(PAHs)，它们已知对人类健康和自然生物群的有害影响，包括诱发癌症。ENPs的反应性可能对人类和其他生命形式造成潜在危害，在环境中，它们可能与多环芳烃等其他污染物以各种可能的组合出现。它们可以以不同的方式互动和行为，而不是当它们独自出现在环境中时。然而，它们潜在的交互作用尚不清楚。在细胞内(生命的最小单位)，它们会对生物分子(如膜、蛋白质和DNA)造成损害。除了ENPs和PAHs与生物分子(如DNA、细胞膜)的直接相互作用外，由此产生的损害可能是通过形成称为自由基的高活性分子来实现的，这些分子参与了许多病理条件，我们的目标是使用特定的技术来测量，但方法还没有适当地开发出来。当它们在不同条件下(如盐度、酸度、氧气水平等)与水接触时，情况尤其如此。单独或与多环芳烃等其他污染物结合使用。我们将在我们的实验室合成ENPs，并将在各种条件下表征它们的特定性质，跟踪它们被贻贝(单独或与多环芳烃结合)的摄取，并在适当的情况下使用分析技术在不同的组织中定位它们。使用两种化学上不同的、广泛使用的与环境相关的ENPs(即C60富勒烯和碳纳米管)，本提案的目的是确定这些ENPs单独或与与环境相关的多环芳烃结合在一起的潜在影响。我们将使用一系列生物学措施，包括对DNA或基因的破坏，这是生命的蓝图，并确定单个或一组基因在不同条件下的行为，这可能会对海洋贻贝的不同器官或组织产生潜在的有害影响。我们将通过改变暴露条件(慢性或急性)来改变产生的损害程度，并将确定抗氧化剂水平以关联影响。还将检测生成的自由基对细胞膜的破坏作用。我们将使用建模技术来结合个体的生物反应，以描绘潜在影响的更大图景。利用分析技术，我们将确定海水和生物体组织中的ENPs和PAHs水平，并将这些水平与观察到的影响相关联。这种方法将有助于我们确定这些化学品对我们健康的潜在风险，并将通知监管机构和行业采取适当行动，以保障人类和环境的健康。我们将使用生成的信息来解释接触ENPs和PAHs的途径，并提出减少任何潜在危害的方法。这也可能在癌症等疾病的治疗中得到应用。我们将与科学界、行业和所有其他利益相关者共享信息。

项目成果

Sources and reactivity of C60-fullerenes in the environment: preliminary investigations

环境中 C60-富勒烯的来源和反应性：初步调查

• 发表时间: 2016
• 作者: Aminot Y

Differentiation-associated urothelial cytochrome P450 oxidoreductase predicates the xenobiotic-metabolizing activity of "luminal" muscle-invasive bladder cancers.

• DOI: 10.1002/mc.22784
• 发表时间: 2018-05
• 期刊: Molecular carcinogenesis
• 影响因子: 4.6
• 作者: Baker SC;Arlt VM;Indra R;Joel M;Stiborová M;Eardley I;Ahmad N;Otto W;Burger M;Rubenwolf P;Phillips DH;Southgate J
• 通讯作者: Southgate J

Combined effects of benzo(a)pyrene and multi-walled carbon nanotubes in Mytilus galloprovincialis tissues: A transcriptomic and immunohistochemical study

苯并(a)芘和多壁碳纳米管在贻贝组织中的联合作用：转录组学和免疫组织化学研究

• 发表时间: 2016
• 作者: Banni M

Interactive effects of carbon nanoparticles and benzo(a)pyrene on marine mussels, Mytilus galloproviancialis

碳纳米粒子和苯并（a）芘对贻贝（Mytilus galloproviancialis）的相互作用

• 发表时间: 2018
• 作者: Audrey Barranger

Impact of genetic modulation of SULT1A enzymes on DNA adduct formation by aristolochic acids and 3-nitrobenzanthrone.

• DOI: 10.1007/s00204-016-1808-6
• 发表时间: 2017-04
• 期刊: Archives of toxicology
• 影响因子: 6.1
• 作者: Arlt VM;Meinl W;Florian S;Nagy E;Barta F;Thomann M;Mrizova I;Krais AM;Liu M;Richards M;Mirza A;Kopka K;Phillips DH;Glatt H;Stiborova M;Schmeiser HH
• 通讯作者: Schmeiser HH