Defining the Deleterious Effects of Environmental Pollutants at a Mechanistic Level

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Humans are constantly exposed to a complex mixture of damaging chemicals in the environment. Young children, especially those that are unborn, and the elderly are most at risk from environmental contaminants. Air pollution is a particular concern and has been linked to 3.7 million excess deaths worldwide each year, with diesel exhaust emissions being a major contributor. Contaminated foodstuffs - such as seafood contaminated by mercury - and pollution of water supplies by heavy metals such as arsenic also play a role, as do lifestyle factors, such as drinking and smoking. The World Health Organisation (WHO) estimates that 23% of global deaths, rising to 36% amongst children under 14 years of age, are attributable to environment factors such as these. Despite these alarming statistics, in most cases we do not understand how pollutants increase risk of disease. Our lack of understanding means that we cannot predict the likely health outcomes of exposure to specific pollutants. Nor are we in a position to develop public health interventions that might reduce the harmful impact of pollutants. This work will test the hypothesis that pollutants associated with diesel engine emissions increase disease risk by causing damage to proteins, fats and DNA, the three major types of chemical that make up our bodies. We will do this using a panel of models we have generated that allow responses to damage to be measured following in vivo exposure. This work will improve our understanding of how diesel exhaust fumes, and facilitate studies into how many other types of pollutants cause disease and also how pollutants exacerbate diseases such as asthma. It will allow us to identify affected organs and cell types and thus to predict the specific health outcomes that are likely to result from exposure to specific chemical mixtures. In the future, the models developed during this study will also allow us to evaluate the effectiveness of public-health interventions designed to reduce the impact of harmful pollutants. Finally, this work will provide us with potential biomarkers (chemicals that can be easily and safely measured in humans) that can be used to assess public exposure to dangerous levels of pollution.