title: Gene expression profiling of A549 cells exposed to Milan PM2.5.
abstract: BACKGROUND
  Particulate matter (PM) has been associated to adverse health effects in exposed population and DNA damage has been extensively reported in in vitro systems exposed to fine PM (PM2.5). The ability to induce gene expression profile modulation, production of reactive oxygen species (ROS) and strand breaks to DNA molecules has been investigated in A549 cells exposed to winter and summer Milan PM2.5.
  
  
  RESULTS
  A549 cells, exposed to 10 μg/cm(2) of both winter and summer PM2.5, showed increased cytotoxicity at 24h and a significant increase of ROS at 3h of treatment. Despite these similar effects winter PM induced a higher number of gene modulation in comparison with summer PM. Both PMs modulated genes related to the response to xenobiotic stimuli (CYP1A1, CYP1B1, TIPARP, ALDH1A3, AHRR) and to the cell-cell signalling (GREM1) pathways with winter PM2.5 inducing higher fold increases. Moreover the winter fraction modulated also JUN (cell-cell signalling), GDF15, SIPA1L2 (signal transduction), and HMOX1 (oxidative stress). Two genes, epiregulin (EREG) and FOS-like antigen1 (FOSL1), were significantly up-regulated by summer PM2.5. The results obtained with the microarray approach have been confirmed by qPCR and by the analysis of CYP1B1 expression. Comet assay evidenced that winter PM2.5 induced more DNA strand breaks than the summer one.
  
  
  CONCLUSIONS
  Winter PM2.5 is able to induce gene expression alteration, ROS production and DNA damage. These effects are likely to be related to the CYP enzyme activation in response to the polycyclic aromatic hydrocarbons (PAHs) adsorbed on particle surface.
authors.affiliation: POLARIS Research Center, Department of Environmental Science, University of Milano Bicocca, 1, piazza della Scienza, I-20126 Milan, Italy. maurizio.gualtieri@unimib.it
authors.forename: Maurizio
authors.initials: M
authors.lastname: Gualtieri
authors.forename: Eleonora
authors.initials: E
authors.lastname: Longhin
authors.forename: Michela
authors.initials: M
authors.lastname: Mattioli
authors.forename: Paride
authors.initials: P
authors.lastname: Mantecca
authors.forename: Valentina
authors.initials: V
authors.lastname: Tinaglia
authors.forename: Eleonora
authors.initials: E
authors.lastname: Mangano
authors.forename: Maria Carla
authors.initials: MC
authors.lastname: Proverbio
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Bestetti
authors.forename: Marina
authors.initials: M
authors.lastname: Camatini
authors.forename: Cristina
authors.initials: C
authors.lastname: Battaglia
mesh_terms: D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics / Q000378:metabolism; D015153:Blotting, Western; D002460:Cell Line; D002470:Cell Survival / Q000502:physiology; D020552:Comet Assay; D065633:Cytochrome P-450 CYP1B1; D004249:DNA Damage; D004781:Environmental Exposure / Q000009:adverse effects*; D004847:Epithelial Cells; D005434:Flow Cytometry; D015870:Gene Expression / Q000187:drug effects*; D020869:Gene Expression Profiling / Q000379:methods; D006801:Humans; D007558:Italy; D020411:Oligonucleotide Array Sequence Analysis; D052638:Particulate Matter / Q000737:chemistry / Q000633:toxicity*; D011084:Polycyclic Aromatic Hydrocarbons / Q000633:toxicity; D012313:RNA / Q000737:chemistry / Q000235:genetics; D017382:Reactive Oxygen Species / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012621:Seasons; D014505:Urban Population
chemical_list: D052638:Particulate Matter; D011084:Polycyclic Aromatic Hydrocarbons; D017382:Reactive Oxygen Species; D012313:RNA; D001189:Aryl Hydrocarbon Hydroxylases; C585496:CYP1B1 protein, human; D065633:Cytochrome P-450 CYP1B1