Mediation of the association between polycyclic aromatic hydrocarbons exposure and telomere attrition by oxidative stress: A prospective cohort study

Abstract

Previous studies have reported associations between polycyclic aromatic hydrocarbons (PAHs) exposure and telomere attrition, but the underlying mechanisms remain to be elucidated. This study aimed to explore the mediation role of oxidative stress on the effects of PAHs exposure on telomere attrition in a cohort study of 1180 coke-oven workers. We determined baseline urinary concentrations of ten urinary PAH metabolites, two oxidative stress biomarkers [8-hydroxydeoxyguanosine (8-OHdG) and 8-iso-prostaglandin-F2α (8-isoPGF2α)] and peripheral leukocytes telomere length (TL) in both baseline and follow-up visits. Mediation analysis was applied to assess effects of oxidative stress biomarkers on the PAHs-TL attrition associations. The baseline 8-OHdG had a significant dose-response relationship with TL decline [β(95 %CI) = 0.07(0.03-0.12), P = 0.001] and TL ratio [β(95 %CI)]=0.07 (0.02-0.12), P = 0.003]. Mediation analyses indicated that 8-OHdG mediated a separate 39.1 %, 47.0 %, 43.3 %, and 58.0 % of the associations between 1-hydroxynaphthalene (1-OHNa), 2-OHNa, ΣOHNa, 1-hydroxypyrene (1-OHP) and TL decline (P = 0.016, 0.008, 0.012, and 0.014, respectively). Additionally, 8-OHdG mediated a separate 44.8 %, 49.4 %, 49.2 %, and 35.5 % of the associations between 1-OHNa, 2-OHNa, ΣOHNa, 1-OHP and TL ratio (P = 0.012, 0.008, 0.012, and 0.046, respectively). Our study proposed the positive association of 8-OHdG with TL attrition and revealed the mediation roles of 8-OHdG in PAHs-TL attrition associations.

Keywords: Mediation; Oxidative stress; Polycyclic aromatic hydrocarbons; Prospective cohort study; Telomere shortening.