Polycyclic Aromatic Hydrocarbons-Associated MicroRNAs and Their Interactions with the Environment: Influences on Oxidative DNA Damage and Lipid Peroxidation in Coke Oven Workers
Polycyclic Aromatic Hydrocarbons-Associated MicroRNAs and Their Interactions with the Environment: Influences on Oxidative DNA Damage and Lipid Peroxidation in Coke Oven Workers
复制标题
DOI：
10.1021/es4055516
复制
发表时间：
2014-04-01
影响因子：
11.4
通讯作者：
Wu, Tangchun
中科院分区：
文献类型：
--
作者：
Deng, Qifei;Dai, Xiayun;Wu, Tangchun
我们之前鉴定了五种多环芳烃（PAHs）相关的microRNAs（miRNAs），发现它们与染色体损伤有关。由于氧化损伤是多种多环芳烃相关疾病的共同原因，我们进一步研究了这些miRNA及其与环境因素的相互作用对氧化DNA损伤和脂质过氧化的影响。我们测量了多环芳烃内暴露生物标志物[尿中单羟基-多环芳烃（OH-PAT-Is）和血浆苯并[a]芘-r-7，t-8，t-9，c-10-四氢四醇-白蛋白（BPDE-Alb）加合物]，PAH相关血浆miRNA的表达水平（miR-24-3p、miR-27a-3p、miR-142-5p、miR-28-5p和miR-150-5p），以及氧化性DNA损伤[8-羟基脱氧鸟苷（8-OH-dG）]和脂质过氧化[8-异前列腺素-F2 α]的尿生物标志物（8-iso-PGF_2 α）]测定。这些miRNAs与8-OH-dG（β> 0）的剂量反应增加和8-iso-PGF 2 α（β < 0）的剂量反应减少相关，尤其是在多环芳烃暴露水平较低的工人、非吸烟者和非饮酒者中。这些miRNA与Sigma OH-PAH和BPDE-Alb加合物拮抗性相互作用（β（相互作用）< 0），与饮酒状态协同作用（β（相互作用）> 0），影响8-OH-dG，而它们与BPDE-Alb加合物协同作用（β（相互作用）> 0），与吸烟状态拮抗性相互作用（β（相互作用）< 0），影响8-iso-PGF 2 α。我们的研究结果表明，miRNAs及其与环境因素的相互作用可能是新的机制介导的多环芳烃暴露对DNA氧化损伤和脂质过氧化的影响。
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-PAT-Is) 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 alpha (8-iso-PGF2 alpha)] in 365 healthy male coke oven workers. These miRNAs were associated with a dose response increase in 8-OH-dG (beta > 0), and with a dose-response decrease in 8-iso-PGF2 alpha (beta < 0), especially in workers with lower PAHs exposure levels, in nonsmokers, and in nondrinkers. These miRNAs interacted antagonistically with Sigma OH-PAHs and BPDE-Alb adducts (beta(interaction) < 0) and synergistically with drinking status ((beta(interaction) > 0) to influence 8-OH-dG, while they interacted synergistically with BPDE-Alb adducts ((beta(interaction) > 0) and antagonistically with smoking status ((beta(interaction) < 0) to influence 8-iso-PGF2 alpha. 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.