Department of Occupational & Environmental Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, China; Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, Wuhan, Hubei, 430030, China; State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, China.
Department of Occupational & Environmental Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, China; Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, Wuhan, Hubei, 430030, China; State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, China.
Environ Pollut. 2020 Oct;265(Pt A):114860. doi: 10.1016/j.envpol.2020.114860. Epub 2020 May 28.
Polycyclic aromatic hydrocarbon (PAH) exposure has been considered a risk factor for cardiovascular diseases (CVD), whereas possible mechanisms for this association have not been fully understood. This study focused on exploring the potential effect of oxidatively damaged DNA on the relationships between PAH exposure and the 10-year atherosclerotic CVD (ASCVD) risk. Urinary levels of monohydroxy PAH metabolites (OH-PAHs) and 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG, the typical biomarker for oxidatively damaged DNA) were measured among 3052 subjects in the baseline of the Wuhan-Zhuhai cohort. The relationships between urinary OH-PAHs, 8-oxodG and 10-year risk of ASCVD were analyzed by linear mixed models and logistic regression models, respectively. The mediation analysis was further applied to explore the role of 8-oxodG in the relationship between urinary OH-PAHs and 10-year ASCVD risk. After controlling for potential confounders, the log-transformed level of total urinary low molecular weight OH-PAHs (∑LMW OH-PAHs) was significantly associated with an elevated risk of 10-year ASCVD [odds ratio (OR) = 1.222, 95% confidence interval (CI): 1.065-1.402]. More specifically, significantly positive dose-response relationships between total urinary hydroxynaphthalene (∑OHNa), hydroxyfluorene (∑OHFlu), hydroxyphenanthrene (∑OHPh) and 10-year ASCVD risk were observed (all P for trend <0.05). We also found positive relationships between urinary OH-PAH levels and 8-oxodG, as well as between urinary 8-oxodG levels and 10-year risk of ASCVD. Moreover, mediation analyses indicated that urinary 8-oxodG mediated 14.49%, 12.62% and 10.55% of the associations between urinary ∑LMW OH-PAHs, ∑OHNa, ∑OHFlu and 10-year ASCVD risk, respectively. These findings suggest that the oxidatively damaged DNA pathway may be a possible mechanism underlying PAH-associated ASCVD risk elevation.
多环芳烃（PAH）暴露已被认为是心血管疾病（CVD）的危险因素，而这种关联的可能机制尚未完全阐明。本研究旨在探讨氧化损伤 DNA 对 PAH 暴露与 10 年动脉粥样硬化性 CVD（ASCVD）风险之间关系的潜在影响。在武汉-珠海队列的基线中，测量了 3052 名受试者的单羟基 PAH 代谢物（OH-PAHs）和 8-氧-7,8-二氢-2'-脱氧鸟苷（8-oxodG，氧化损伤 DNA 的典型生物标志物）的尿水平。线性混合模型和逻辑回归模型分别分析了尿 OH-PAHs、8-oxodG 与 10 年 ASCVD 风险之间的关系。进一步应用中介分析探讨了 8-oxodG 在尿 OH-PAHs 与 10 年 ASCVD 风险之间关系中的作用。在控制潜在混杂因素后，总尿低分子量 OH-PAHs（∑LMW OH-PAHs）的对数转换水平与 10 年 ASCVD 风险升高显著相关[比值比（OR）=1.222，95%置信区间（CI）：1.065-1.402]。更具体地说，总尿羟基萘（∑OHNa）、羟基芴（∑OHFlu）和羟基菲（∑OHPh）与 10 年 ASCVD 风险之间观察到显著的正剂量反应关系（所有趋势 P 值<0.05）。我们还发现尿 OH-PAH 水平与 8-oxodG 之间以及尿 8-oxodG 水平与 10 年 ASCVD 风险之间存在正相关关系。此外，中介分析表明，尿 8-oxodG 介导了尿∑LMW OH-PAHs、∑OHNa、∑OHFlu 与 10 年 ASCVD 风险之间的关联的 14.49%、12.62%和 10.55%。这些发现表明，氧化损伤 DNA 途径可能是 PAH 相关 ASCVD 风险升高的潜在机制。
