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

在1-100纳米（一纳米是一米的十亿分之一）范围内的粒子被称为纳米粒子，广泛存在于环境中。但是，人造纳米粒子（即工程纳米粒子或ENPs）具有巨大的技术和经济利益。它们在环境修复、医疗和消费产品方面具有广泛的潜在应用。enp的小尺寸赋予它们特殊的化学性质，使它们具有潜在的反应性。这些颗粒自愿或非自愿地排放到环境中，与柴油废气、石油泄漏和泄漏、烟草烟雾等其他污染物一样。这些化学物质统称为多环芳烃（PAHs），已知它们对人类健康和自然生物群有有害影响，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，它们可能与其他污染物（如多环芳烃）以所有可能的组合发生。它们可以以不同的方式互动和行为，而不是单独存在于环境中。然而，它们潜在的相互作用尚不清楚。在细胞（最小的生命单位）内，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（例如DNA，细胞膜）的直接相互作用外，所产生的损伤可能是通过形成称为自由基的高活性分子而产生的，自由基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，其方法尚未得到适当的开发。当它们在不同条件下（例如盐度、酸度、氧含量等）单独或与其他污染物（如多环芳烃）结合接触时，尤其如此。我们将在实验室中合成ENPs，并将在各种条件下表征它们的特定特性，跟踪贻贝对它们的吸收（单独或与多环芳烃结合），并在适当的情况下使用分析技术将它们定位在不同的组织中。使用两种化学上不同，广泛使用的环境相关的ENPs（即C60富勒烯和碳纳米管），本提案的目的是确定这些ENPs单独或与环境相关的多环芳烃组合的潜在影响。我们将使用一系列生物学测量方法，包括对DNA或基因（生命蓝图）的损害，并确定单个或一组基因在不同条件下的行为，这些条件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）来改变所产生的损害程度，并将确定抗氧化剂水平以关联影响。所产生的自由基对细胞膜的破坏作用也将被检查。我们将使用建模技术来整合个体生物反应，以绘制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ENPs和PAHs的水平，并将这些水平与观察到的影响联系起来。这种方法将帮助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暴露于ENPs和PAHs的途径，并提出减少任何潜在危害的方法。这也可以应用于癌症等疾病的治疗。我们将与科学界、工业界和所有其他利益相关者分享这些信息。

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.