title: Effects of particulate matter on genomic DNA methylation content and iNOS promoter methylation.
abstract: BACKGROUND
  Altered patterns of gene expression mediate the effects of particulate matter (PM) on human health, but mechanisms through which PM modifies gene expression are largely undetermined.
  
  
  OBJECTIVE
  We aimed at identifying short- and long-term effects of PM exposure on DNA methylation, a major genomic mechanism of gene expression control, in workers in an electric furnace steel plant with well-characterized exposure to PM with aerodynamic diameters < 10 microm (PM(10)).
  
  
  METHODS
  We measured global genomic DNA methylation content estimated in Alu and long interspersed nuclear element-1 (LINE-1) repeated elements, and promoter DNA methylation of iNOS (inducible nitric oxide synthase), a gene suppressed by DNA methylation and induced by PM exposure in blood leukocytes. Quantitative DNA methylation analysis was performed through bisulfite PCR pyrosequencing on blood DNA obtained from 63 workers on the first day of a work week (baseline, after 2 days off work) and after 3 days of work (postexposure). Individual PM(10) exposure was between 73.4 and 1,220 microg/m(3).
  
  
  RESULTS
  Global methylation content estimated in Alu and LINE-1 repeated elements did not show changes in postexposure measures compared with baseline. PM(10) exposure levels were negatively associated with methylation in both Alu [beta = -0.19 %5-methylcytosine (%5mC); p = 0.04] and LINE-1 [beta = -0.34 %5mC; p = 0.04], likely reflecting long-term PM(10) effects. iNOS promoter DNA methylation was significantly lower in postexposure blood samples compared with baseline (difference = -0.61 %5mC; p = 0.02).
  
  
  CONCLUSIONS
  We observed changes in global and gene specific methylation that should be further characterized in future investigations on the effects of PM.
authors.affiliation: Laboratory of Environmental Epigenetics, Department of Preventive Medicine, University of Milan and IRCCS Maggiore Hospital, Milan, Italy.
authors.forename: Letizia
authors.initials: L
authors.lastname: Tarantini
authors.forename: Matteo
authors.initials: M
authors.lastname: Bonzini
authors.forename: Pietro
authors.initials: P
authors.lastname: Apostoli
authors.forename: Valeria
authors.initials: V
authors.lastname: Pegoraro
authors.forename: Valentina
authors.initials: V
authors.lastname: Bollati
authors.forename: Barbara
authors.initials: B
authors.lastname: Marinelli
authors.forename: Laura
authors.initials: L
authors.lastname: Cantone
authors.forename: Giovanna
authors.initials: G
authors.lastname: Rizzo
authors.forename: Lifang
authors.initials: L
authors.lastname: Hou
authors.forename: Joel
authors.initials: J
authors.lastname: Schwartz
authors.forename: Pier Alberto
authors.initials: PA
authors.lastname: Bertazzi
authors.forename: Andrea
authors.initials: A
authors.lastname: Baccarelli
mesh_terms: D000328:Adult; D019175:DNA Methylation / Q000187:drug effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D052247:Nitric Oxide Synthase Type II / Q000235:genetics*; D052638:Particulate Matter / Q000633:toxicity*; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic / Q000235:genetics*
chemical_list: D052638:Particulate Matter; D052247:Nitric Oxide Synthase Type II