Effects of particulate matter on genomic DNA methylation content and iNOS promoter methylation

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

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 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.

Keywords: DNA methylation; epigenetics; etiology; interspersed repetitive sequences; nitric oxide synthase; particulate matter.

Figures

Figure 1
Figure 1
Long-term effects of PM10 on blood DNA methylation in Alu (A) and LINE-1 (B) repeated elements. PM10 concentrations, taken as a measure of usual exposure to particles, was examined in relation to all the measures of DNA methylation performed in the study, regardless of whether they were measured on samples taken on the first day of work (i.e., after 2 days off) or after 3 consecutive days of exposure to PM10 in the plant. Abbreviations: adj, adjusted; nonadj, nonadjusted. Data points represent the average of DNA.

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