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

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.

Research on the potential for detrimental effects with environmental safety implications of engineered nanoparticles (ENPs) has a global impact across both government and industry. In addition, it also has an important impact on the public understanding of the benefits of these new technologies, as the nanoparticles will enter the environment through various sources.

The proposed research will facilitate critical evaluation of the internationally agreed process for the evaluation of potential effects and toxicity testing to determine whether the current legislative test methods are fit for purpose and are acceptable to industry. The proposal will also identify the opportunities, nationally and internationally, for research priorities to advance the interdisciplinary science and influence governmental policies and international initiatives (through e.g. OECD, ISO, EU, US EPA) to determine safe levels of exposures either for environmental or for work place exposures through different routes. The results generated in this proposal will serve as a spring board to elucidate potential interactive toxic effects along with providing critical bioavailability/uptake mechanisms and potential effects at different levels of biological organisation (molecular to individual levels), to afford the opportunity to consider which level is best to select for hazard and risk identification.

The combined effects of contaminants have been a burning issue in both scientific and regulatory communities to understand the mechanisms of actions at biological levels and to protect both our and environmental health. In a broader perspective, the proposal will help to elucidate the fundamental understanding to fill the knowledge gaps towards building a consensus approach to assess the potential biological effects of ENPs, either alone or in combination with other ubiquitous contaminants/ pollutants such as carcinogenic PAHs.

This interdisciplinary study will have an effective impact on the academic community who aim to elucidate a fundamental understanding of anthropogenic chemicals with living systems especially relating to the application of newly emerging technologies. The information could be translated to other biological systems including humans, given that a large number of genes involved in the processing of stress related response are evolutionary and are highly conserved.

The results generated could also benefit those industries aiming to develop products in areas such as photodynamic therapy and nano-medicine. The protocols developed to estimate the free radical generation could benefit those industries which are interested in sun protection, polymorphic light eruption and other UV sensitivities. Members of the project team are involved in synthesis of novel nanomaterials and uses of purpose-made nano-materials could further explore their applications in other areas (e.g. water treatment, development of photovoltaic cells). The project will also impact on advancement of analytical capabilities to determine levels of contaminants in biological matrices. The deliverables of the project will also impact on the public awareness for new technologies and impact the younger generation to opt for scientific careers to progress our future.