Effects of Particulate Matter on Genomic DNA Methylation Content and <i>iNOS</i> Promoter Methylation

TLDR

Particulate matter influences human health by altering gene expression, yet the mechanisms by which PM modifies gene expression remain largely unknown. This study aimed to determine the short‑ and long‑term effects of PM10 exposure on DNA methylation in steel‑plant workers. Researchers measured global Alu and LINE‑1 methylation and iNOS promoter methylation using bisulfite‑PCR pyrosequencing on blood samples from 63 workers at baseline and after three workdays. PM10 exposure was linked to decreased methylation of Alu and LINE‑1 elements and to lower iNOS promoter methylation post‑exposure, suggesting long‑term epigenetic changes induced by PM.

Abstract

BackgroundAltered 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.ObjectivesWe 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).MethodsWe 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.ResultsGlobal 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).ConclusionsWe observed changes in global and gene specific methylation that should be further characterized in future investigations on the effects of PM.