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

BACKGROUND: 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. OBJECTIVES: 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. METHODS: We measured LTL, and mRNA expression and promoter DNA methylation of the telomerase catalytic enzyme (hTERT) in blood samples obtained from 63 steel workers on the first day of a workweek (baseline) and after three days of work (post-exposure). RESULTS: LTL was significantly increased in post-exposure (Mean=1.43, SD=0.51) compared to baseline samples (Mean=1.23, SD=0.28; p-value<0.001). Post-exposure LTL was positively associated with PM10 (β=0.30, p-value=0.002 for a 90th-10th percentile exposure change) and PM1 (β=0.29, p-value=0.042) exposure levels in regression models adjusting for multiple covariates. hTERT expression was lower in post-exposure (Mean=1.31, SD=0.75) compared to baseline samples (Mean=1.68, SD=0.86; p-value<0.001), but the decrease in hTERT expression did not show a dose-response relationship with PM. No exposure-related differences were found in the methylation of any of the CpG sites investigated in the hTERT promoter. CONCLUSIONS: 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.