Open Access Research

Ambient PM exposure and DNA methylation in tumor suppressor genes: a cross-sectional study

Lifang Hou12*, Xiao Zhang1, Letizia Tarantini3, Francesco Nordio37, Matteo Bonzini4, Laura Angelici3, Barbara Marinelli3, Giovanna Rizzo3, Laura Cantone3, Pietro Apostoli5, Pier Alberto Bertazzi3 and Andrea Baccarelli6

Author Affiliations

1 Department of Preventive Medicine, Feinberg School of Medicine, Northwestern University, 680 N. Lakeshore Drive, Chicago, 60611, USA

2 Robert H. Lurie Comprehensive Cancer Center Feinberg School of Medicine, Northwestern University, 303 E Superior Street, Chicago, 60611, USA

3 Department of Preventive Medicine and Department of Environmental and Occupational Health, University of Milan and IRCCS Maggiore Hospital, Mangiagalli and Regina Elena Foundation, Via Pace 9, Milan, 20122, Italy

4 Department of Clinical and Biological Sciences, University of Insubria, Viale Borri 57, Varese, 21100 Italy

5 Department of Experimental and Applied Medicine, Occupational Medicine and Industrial Hygiene, University of Brescia, P.le Spedali Civili 1, Brescia, 25123, Italy

6 Laboratory of Environmental Epigenetics, Department of Environmental Health, Harvard School of Public Health, 665 Huntington Ave, Boston, 02115, USA

7 Department of Clinical Medicine, Nephrology and Health Science, University of Parma Medical School, Via Gramsci 14, Parma, 43126, Italy

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Particle and Fibre Toxicology 2011, 8:25  doi:10.1186/1743-8977-8-25

Published: 30 August 2011


Exposure to ambient air particles matter (PM) has been associated with increased risk of lung cancer. Aberrant tumor suppressor gene promoter methylation has emerged as a promising biomarker for cancers, including lung cancer. Whether exposure to PM is associated with peripheral blood leukocyte (PBL) DNA methylation in tumor suppressor genes has not been evaluated. In 63 male healthy steel workers with well-characterized exposure to metal-rich particles nearby Brescia, Italy, we evaluated whether exposure to PM and metal components was associated with PBL DNA methylation in 4 tumor suppressor genes (i.e., APC, p16, p53 and RASSF1A). Blood samples were obtained on the 1st (baseline) and 4th day (post-exposure) of the same work week and DNA methylation was measured using pyrosequencing. A linear mixed model was used to examine the correlations of the exposure with promoter methylation levels. Mean promoter DNA methylation levels of APC or p16 were significantly higher in post-exposure samples compared to that in baseline samples (p-values = 0.005 for APC, and p-value = 0.006 for p16). By contrast, the mean levels of p53 or RASSF1A promoter methylation was decreased in post-exposure samples compared to that in baseline samples (p-value = 0.015 for p53; and p-value < 0.001 for RASSF1A). In post-exposure samples, APC methylation was positively associated with PM10 (β = 0.27, 95% CI: 0.13-0.40), and PM1 (β = 0.23, 95% CI: 0.09-0.38). In summary, ambient PM exposure was associated with PBL DNA methylation levels of tumor suppressor genes of APC, p16, p53 and RASSF1A, suggesting that such methylation alterations may reflect processes related to PM-induced lung carcinogenesis.