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芳香烃受体表达在多环芳烃暴露与中国职业工人氧化 DNA 损伤之间的中介效应。

Mediation effect of AhR expression between polycyclic aromatic hydrocarbons exposure and oxidative DNA damage among Chinese occupational workers.

机构信息

Department of Occupational Health, School of Public Health, Shanxi Medical University, Taiyuan, 030001, China.

School of Public Health, The University of Hong Kong, Hong Kong, China; Institute of Epidemiology and Statistics, School of Public Health, Lanzhou University, Lanzhou, Gansu, 730000, China.

出版信息

Environ Pollut. 2018 Dec;243(Pt B):972-977. doi: 10.1016/j.envpol.2018.09.014. Epub 2018 Sep 17.

DOI:10.1016/j.envpol.2018.09.014
PMID:30248604
Abstract

Polycyclic aromatic hydrocarbons (PAH) are well-known to be carcinogenic and the mechanisms that it contributes to oxidative DNA damage and aryl hydrocarbon receptor (AhR)-dependent induction are also well understood. However, little is known about the associations between PAH exposure, AhR expression, and oxidative DNA damage. We investigated their associations of AhR expression and oxidative DNA damage related to PAH exposure among 310 workers from a coke-oven plant in China. Urine biomarkers of PAH exposure (2-hydroxynaphthalene, 2-NAP; 2-hydroxyfluorene, 2-FLU; 9-hydroxyphenanthren, 9-PHE; and 1-hydroxypyrene, 1-OHP) and a marker of oxidative damage (8-hydroxy- 2'- deoxyguanosine, 8-OHdG) were measured by high performance liquid chromatography. AhR expression in venous blood was measured by reverse transcription -polymerase chain reaction. The results showed that increasing levels of urinary 1-OHP was positively associated with high 8-OHdG (OR (95% CI) was 4.01 (1.41-11.45) for 4th quartile, compared with 1st quartile, P for trend = 0.013). The similar associations were also found between urinary 1-OHP and high-AhR expressions (4th vs. 1st quartile = 3.50, 95% CI: 1.24-9.87, P for trend = 0.029). A significant association between AhR expression and high 8-OHdG was also found (4th vs. 1st quartile = 2.44, 95% CI: 1.05-5.70, P for trend = 0.027). In addition, mediation analysis showed the AhR expression could explain 35.9% of the association of oxidative DNA damage related to PAH exposure. Our findings implicated that the association between PAH exposure and oxidative DNA damage may be mediated by AhR expression among Chinese occupational workers.

摘要

多环芳烃(PAH)是众所周知的致癌物质,其导致氧化 DNA 损伤和芳烃受体(AhR)依赖性诱导的机制也已得到充分理解。然而,对于 PAH 暴露、AhR 表达与氧化 DNA 损伤之间的关联知之甚少。我们在中国一家焦炉厂的 310 名工人中调查了 AhR 表达与与 PAH 暴露相关的氧化 DNA 损伤之间的关联。通过高效液相色谱法测量了 PAH 暴露的尿生物标志物(2-羟基萘,2-NAP;2-羟基芴,2-FLU;9-羟基菲,9-PHE;和 1-羟基芘,1-OHP)和氧化损伤标志物(8-羟基-2'-脱氧鸟苷,8-OHdG)。通过逆转录-聚合酶链反应测量静脉血中的 AhR 表达。结果表明,尿 1-OHP 水平升高与高 8-OHdG 呈正相关(第 4 四分位与第 1 四分位相比,OR(95%CI)为 4.01(1.41-11.45),P 趋势=0.013)。在尿 1-OHP 与高 AhR 表达之间也发现了类似的关联(第 4 四分位与第 1 四分位相比,4th vs. 1st quartile = 3.50,95% CI:1.24-9.87,P 趋势=0.029)。还发现 AhR 表达与高 8-OHdG 之间存在显著关联(第 4 四分位与第 1 四分位相比,4th vs. 1st quartile = 2.44,95% CI:1.05-5.70,P 趋势=0.027)。此外,中介分析表明,AhR 表达可以解释 PAH 暴露与氧化 DNA 损伤相关的关联的 35.9%。我们的研究结果表明,在接触 PAH 的中国职业工人中,PAH 暴露与氧化 DNA 损伤之间的关联可能是由 AhR 表达介导的。

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