Telomere Length and Particulate Matter Exposure in Steel Workers

Abstract

ISEE-0664 Background and Objective: Shortening of telomeres is a marker of biological aging that has been related with cancer, cardiovascular diseases, and ambient particle exposure. However, other conditions inducing oxidative-stress and inflammation cause telomere lengthening, possibly due to cell maturation and proliferation of inflammatory cells. Telomere length is maintained by telomerase, which is induced by methylation in its promoter. We investigated the effects of exposure to airborne particulate matter (PM) on leukocyte telomere length (LTL), telomerase expression, and telomerase promoter methylation in blood DNA from foundry workers exposed to a wide range of PM level. Methods: We measured relative LTL and telomerase expression using RT- PCR in 63 male foundry workers on the first day of a workweek (T0) and after three days of work (T1). We measured telomerase promoter methylation through PCR-Pyrosequencing. Individual exposure to PM was estimated using area measurements and time-activity records. Results: LTL was significantly increased after three days of work (T1: Mean = 1.43, SE = 0.07) compared with the baseline measurement (T0: Mean = 1.22, SE = 0.04; P-value<0.001). In T1 samples, LTL was positively associated with PM10 and PM1 levels in unadjusted (β = 0.26, P = 0.002 and β = 0.25, P = 0.04), as well as in multivariate regression models (β = 0.27, P = 0.002 and β = 0.28, P = 0.02) adjusting for age, BMI, smoking and cigarettes/day. Telomerase expression was significantly decreased between the beginning and the end of time work (T0: Mean = 1.68, SE = 0.11; T1: Mean = 1.33, SE = 0.10; P-value<0.001), and this decrease was associated with lower levels of telomerase promoter DNA methylation (T0: Mean = 92.9 %5mC, SE = 0.21; T1: Mean = 92.5, SE = 0.21; P-value = 0.02). Conclusion: Our results show that short-term exposure to metal particles, at variance with previous data on ambient particles, causes rapid changes in blood LTL, potentially reflecting clonal expansion and selection of inflammatory cell types. Telomerase expression was decreased in post-exposure samples possibly as a result of lower telomerase promoter methylation.