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Theme 2: Project 4 - Genotoxicity of air pollutants
Air pollution is carcinogenic. Genotoxic components of polluted air can interact with cellular macromolecules to form adducts. High resolution mass spectrometry affords the opportunity to conduct global analyses of DNA and protein adducts (adductomics) to determine the normal variation in both human populations and model systems and then to inform on mechanisms of adversity of chemicals (or combinations of chemicals) of concern. Mass spectrometry will be employed in biomonitoring of the population to identify potential hazards and determine exposures. A major source of nitropolycyclic aromatic hydrocarbons (nitro-PAHs) is diesel combustion.
We aim to develop and refine sensitive analytical methods to measure diesel-specific nitro-PAHs in urban air particulate matter. We aim to examine the effect of particle-bound polycyclic aromatic hydrocarbons (PAHs) and nitro-PAHs on pulmonary inflammation and DNA alteration, alone and in combination with aeroallergens. We will develop co-culture systems for inflammatory responses, analogous to those in Project 4 for allergic responses, involving epithelial cells, macrophages and neutrophils. Responses to challenge with ambient air particulate matter, diesel exhaust particles, selected PAHs and nitro-PAHs and complex mixture of them will be determined, including DNA adduct formation, changes in gene expression of xenobiotic metabolising enzymes (XMEs) and changes in expression of markers of genetic damage and inflammatory response.