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Letizia Tarantini,¹ Matteo Bonzini,¹ Pietro Apostoli,² Valeria Pegoraro,¹ Valentina Bollati,¹ Barbara Marinelli,¹ Laura Cantone,¹ Giovanna Rizzo,¹ Lifang Hou,³ Joel Schwartz,⁴ Pier Alberto Bertazzi,¹ and Andrea Baccarelli^1,4

¹Laboratory of Environmental Epigenetics, Department of Preventive Medicine and Department of Environmental and Occupational Health, University of Milan and IRCCS Maggiore Hospital, Mangiagalli and Regina Elena Foundation, Milan, Italy; ²Department of Experimental and Applied Medicine, Occupational Medicine and Industrial Hygiene, University of Brescia, Brescia, Italy; ³Department of Preventive Medicine, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA; ⁴Exposure, Epidemiology and Risk Program, Department of Environmental Health, Harvard School of Public Health, Boston, Massachusetts, USA

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.

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.

Key words: DNA methylation, epigenetics, etiology, interspersed repetitive sequences, nitric oxide synthase, particulate matter. Environ Health Perspect 117:217–222 (2009) . doi:10.1289/ehp.11898 available via http://dx.doi.org/ [Online 26 September 2008]

Address correspondence to A. Baccarelli, Laboratory of Environmental Epigenetics, Department of Environmental and Occupational Health, University of Milan and Maggiore Hospital, Mangiagalli and Regina Elena Foundation, Via San Barnaba 8, 20122 Milan, Italy. Telephone: 39 02 503 20145. Fax: 39 02 503 20103. E-mail: andrea.baccarelli@unimi.it

This work was supported by research grants from the CARIPLO Foundation (2007-5469) and the National Institute of Environmental Health Sciences (ES015172-01) and by additional funding from CARIPLO Foundation and Lombardy Region Research Contracts UniMi 8614/2006 and UniMi 9167/2007.

The authors declare they have no competing financial interests.

Received 4 July 2008 ; accepted 25 September 2008.

An erratum is posted online at http://www.ehponline.org/docs/2009/117-4/errata1.html.