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Polycyclic Aromatic Hydrocarbons-Associated MicroRNAs and Their Interactions with the Environment: Influences on Oxidative DNA Damage and Lipid Peroxidation in Coke Oven Workers
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文摘
We previously identified five polycyclic aromatic hydrocarbons (PAHs)-associated microRNAs (miRNAs) and found they were associated with chromosome damage. As oxidative damage is the common contributory cause of various PAHs-related diseases, we further investigated the influences of these miRNAs and their interactions with environmental factors on oxidative DNA damage and lipid peroxidation. We measured PAHs internal exposure biomarkers [urinary monohydroxy-PAHs (OH-PAHs) and plasma benzo[a]pyrene-r-7,t-8,t-9,c-10-tetrahydotetrol-albumin (BPDE-Alb) adducts], the expression levels of PAHs-associated plasma miRNAs (miR-24-3p, miR-27a-3p, miR-142-5p, miR-28-5p, and miR-150-5p), and urinary biomarkers of oxidative DNA damage [8-hydroxydeoxyguanosine (8-OH-dG)] and lipid peroxidation [8-iso-prostaglandin-F2伪 (8-iso-PGF2伪)] in 365 healthy male coke oven workers. These miRNAs were associated with a dose鈥搑esponse increase in 8-OH-dG (尾 > 0), and with a dose鈥搑esponse decrease in 8-iso-PGF2伪 (尾 < 0), especially in workers with lower PAHs exposure levels, in nonsmokers, and in nondrinkers. These miRNAs interacted antagonistically with 危OH-PAHs and BPDE-Alb adducts (尾interaction < 0) and synergistically with drinking status (尾interaction > 0) to influence 8-OH-dG, while they interacted synergistically with BPDE-Alb adducts (尾interaction > 0) and antagonistically with smoking status (尾interaction < 0) to influence 8-iso-PGF2伪. Our results suggested that miRNAs and their interactions with environmental factors might be novel mechanisms mediating the effects of PAHs exposure on oxidative DNA damage and lipid peroxidation.

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