A Toxicogenomic Comparison of Primary and Photochemically Altered Air Pollutant Mixtures

Abstract

Background: Air pollution contributes significantly to global increases in mortality, particularly within urban environments. Limited knowledge exists on the mechanisms underlying health effects resulting from exposure to pollutant mixtures similar to those occurring in ambient air. In order to clarify the mechanisms underlying exposure effects, toxicogenomic analyses are used to evaluate genomewide transcript responses and map these responses to molecular networks.Objectives: We compared responses induced by exposure to primary pollutants and photochemically altered (PCA) pollutant mixtures representing urban atmospheres to test our hypothesis that exposures to PCA pollutants would show increased modulation of inflammation-associated genes and pathways relative to primary air pollutants.Methods: We used an outdoor environmental irradiation chamber to expose human lung epithelial cells to mixtures representing either primary or PCA pollutants for 4 hr. Transcriptional changes were assessed using microarrays and confirmed using quantitative real-time reverse-transcription polymerase chain reaction (qRT-PCR) on a subset of genes.Results: We found a large difference in the cellular responses to the two pollutant exposures: Primary air pollutants altered the expression levels of 19 genes, whereas PCA pollutants altered 709 genes. Functional and molecular analyses of the altered genes revealed novel pathways, such as hepatocyte nuclear factor 4α, potentially regulating the pollutant responses. Chemical component analysis characterized and confirmed the photochemical transformation of primary air pollutants into PCA air pollutants.Conclusions: Our study shows that the photochemical transformation of primary air pollutants produces altered mixtures that cause significantly greater biological effects than the primary pollutants themselves. These findings suggest that studying individual air pollutants or primary pollutant mixtures may greatly underestimate the adverse health effects caused by air pollution.

In vitro exposure to isoprene-derived secondary organic aerosol by direct deposition and its effects on <i>COX-2</i> and <i>IL-8</i> gene expression

“…Our findings are consistent with other studies showing that photochemical oxidation of similar chemical mixtures increases toxicity in cell culture models and elevates expression of inflammatory biomarker genes (Lichtveld et al, 2012;Rager et al, 2011). Previous in vitro studies using a gasphase-only exposure system have shown that gas-phase products of isoprene photooxidation significantly enhance cytotoxicity and IL-8 expression (Doyle et al, 2004(Doyle et al, , 2007.…”

A rapid assessment of the impact of hazard reduction burning around Sydney, May 2016

“…A study in rats exposed to limonene ozone reaction products did demonstrate induction of inflammation and stress responses, associated with pulmonary pathology, but the exposure was not easily related to the real-world situation (Sunil et al, 2007). Evidence that oxidation of the primary organic aerosol alters (and might potentiate) its toxicity was recently reported by Rager et al (2011), who exposed an immortalized lung epithelial cell line to real world aerosols, either during the morning or the afternoon, the latter reflecting a more oxidized aerosol. The responses of the cells to these differing aerosols were profiled by transcriptomics, revealing a more robust transcriptional response as the primary aerosol aged.…”

Comparison of primary and secondary particle formation from natural gas engine exhaust and of their volatility characteristics

“…Fine particles (< 2.5 µm) are found to cause adverse health effects and premature mortality in people (Dockery and Pope III, 1994;Lelieveld et al, 2015). The relative contribution of primary and secondary particles to these health effects is still unknown, but there are indications that secondary particles can be even more hazardous than primary particles (Künzi et al, 2015;McWhinney et al, 2011;Rager et al, 2011). Therefore, both primary and secondary particle emissions must be taken into consideration when evaluating the health effects of particle emissions.…”