title: 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.
  
  
  OBJECTIVE
  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.
authors.affiliation: Department of Environmental Sciences and Engineering, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
authors.forename: Julia E
authors.initials: JE
authors.lastname: Rager
authors.forename: Kim
authors.initials: K
authors.lastname: Lichtveld
authors.forename: Seth
authors.initials: S
authors.lastname: Ebersviller
authors.forename: Lisa
authors.initials: L
authors.lastname: Smeester
authors.forename: Ilona
authors.initials: I
authors.lastname: Jaspers
authors.forename: Kenneth G
authors.initials: KG
authors.lastname: Sexton
authors.forename: Rebecca C
authors.initials: RC
authors.lastname: Fry
mesh_terms: D000393:Air Pollutants / Q000737:chemistry / Q000494:pharmacology*; D001273:Atmosphere Exposure Chambers; D002460:Cell Line; D045424:Complex Mixtures / Q000737:chemistry / Q000494:pharmacology; D004847:Epithelial Cells / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D006801:Humans; D007249:Inflammation; D016209:Interleukin-8 / Q000032:analysis / Q000096:biosynthesis; D008168:Lung / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D055668:Photochemical Processes; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013472:Sunlight; D043922:Toxicogenetics / Q000379:methods*; D014504:Urban Health
chemical_list: D000393:Air Pollutants; D045424:Complex Mixtures; D016209:Interleukin-8