Effects of Particulate Matter on Genomic DNA Methylation Content and iNOS Promoter Methylation

• Published in: Environmental health perspectives 2009-02, Vol.117 (2), p.217-222
• Main Authors: Tarantini, Letizia, Bonzini, Matteo, Apostoli, Pietro, Pegoraro, Valeria, Bollati, Valentina, Marinelli, Barbara, Cantone, Laura, Rizzo, Giovanna, Hou, Lifang, Schwartz, Joel, Bertazzi, Pier Alberto, Baccarelli, Andrea
• Format: Article
• Language: English
• Subjects: Adult; Aerodynamics; Analysis; Beta; Blood; Body mass index; Cigarette smoking; Copyrights; Deoxyribonucleic acid; DNA; DNA Methylation - drug effects; Electric furnace steels; Environmental health; Foundries; Gene expression; Genes; Genetic aspects; Genomics; Health; Health aspects; Human; Humans; Iron and steel plants; Leukocytes; Male; Methylation; Middle Aged; Nitric oxide; Nitric Oxide Synthase Type II - genetics; Oxides; Particles; Particulate matter; Particulate Matter - toxicity; Piers; Polymerase Chain Reaction; Power plants; Promoter Regions, Genetic - genetics
• ISSN: 0091-6765; 1552-9924
• DOI: 10.1289/ehp.11898

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. Objectives: 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 μm (PM₁₀). 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 PM₁₀ exposure was between 73.4 and 1,220 μg/m³. Results: Global methylation content estimated in Alu and LINE-1 repeated elements did not show changes in postexposure measures compared with baseline. PM₁₀ exposure levels were negatively associated with methylation in both Alu [β = -0.19 %5-methylcytosine (%5mC); p = 0.04] and LINE-1 [β = -0.34 %5mC; p = 0.04], likely reflecting long-term PM₁₀ 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.