Toxicogenomic Study of Indoor and Outdoor Air Chemical Mixtures

Although environmental exposures occur to mixtures of chemicals rather than to individual agents, most of the toxic effects of air pollutants are ascribed to single chemicals. There is a growing feeling in both the scientific and regulatory communities, however that, as the need for better air quality increases, there is also a need for more comprehensive toxicological approaches on the potential impact of complex environmental chemical mixtures on human health. In this perspective, it is expected that the toxicogenomics approach would be the appropriate screening method for assessing biological effects of complex chemical mixtures, allowing us to review the whole spectrum of potential biological response rather than focusing on a pre-defined number of endpoints as in classical toxicological analysis. In this study, we focused on a typical indoor air mixture as defined in the EU-wide review study INDEX and on a mixture of polyaromatic hydrocarbons (PAHs) isolated from urban air in the city of Milan with the aim to identify specific sets of biomarkers for each type of exposure (indoor or outdoor). A human cell line derived from a bronco-pulmonary system (A549) was used. Applying a Total Gene Expression assay by Applied Biosystems Microarrays, we profiled large sets of genes modulated by single mixtures exposure and identified common biochemical pathways and specific molecular responses. Indoor air mixtures induced a higher gene modulation than PAHs, confirming major differences in toxic mode of action of the two mixtures. Indoor air induced primarily modulation of genes associated to protein targeting and localization including in particular cytoskeletal organization; PAHs modulated mostly the expression of genes related to cell motility and gene networks regulating cell-cell signaling, as well as cell proliferation and differentiation. These results provide biological information useful for articulating mechanistic hypotheses of exposure to xenobiotic mixtures and physiological responses.JRC.I.5-Physical and chemical exposure