Effects of Short-Term Exposure to Inhalable Particulate Matter on Telomere Length, Telomerase Expression, and Telomerase Methylation in Steel Workers

Shortened leukocyte telomere length (LTL) is a marker of cardiovascular risk that has been recently associated with long-term exposure to ambient particulate matter (PM). However, LTL is increased during acute inflammation and allows for rapid proliferation of inflammatory cells. Whether short-term exposure to proinflammatory exposures such as PM increases LTL has never been evaluated.We investigated the effects of acute exposure to metal-rich PM on blood LTL, as well as molecular mechanisms contributing to LTL regulation in a group of steel workers with high PM exposure.We measured LTL, as well as mRNA expression and promoter DNA methylation of the telomerase catalytic enzyme gene [human telomerase reverse transcriptase (hTERT)] in blood samples obtained from 63 steel workers on the first day of a workweek (baseline) and after 3 days of work (postexposure).LTL was significantly increased in postexposure (mean \ub1 SD, 1.43 \ub1 0.51) compared with baseline samples (1.23 \ub1 0.28, p-value < 0.001). Postexposure LTL was positively associated with PM\u2081\u2080 (\u3b2 = 0.30, p-value = 0.002 for 90th vs. 10th percentile exposure) and PM\u2081 (\u3b2 = 0.29, p-value = 0.042) exposure levels in regression models adjusting for multiple covariates. hTERT expression was lower in postexposure samples (1.31 \ub1 0.75) than at baseline (1.68 \ub1 0.86, p-value < 0.001), but the decrease in hTERT expression did not show a dose-response relationship with PM. We found no exposure-related differences in the methylation of any of the CpG sites investigated in the hTERT promoter.Short-term exposure to PM caused a rapid increase in blood LTL. The LTL increase did not appear to be mediated by PM-related changes in hTERT expression and methylation

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

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