刘艳丽, 张红杰, 张慧涛, 牛莹莹, 傅晔, 杨瑾. 芳烃受体表达在焦炉工多环芳烃暴露致DNA氧化损伤中的作用[J]. 环境与职业医学, 2018, 35(5): 400-405. DOI: 10.13213/j.cnki.jeom.2018.17585
引用本文: 刘艳丽, 张红杰, 张慧涛, 牛莹莹, 傅晔, 杨瑾. 芳烃受体表达在焦炉工多环芳烃暴露致DNA氧化损伤中的作用[J]. 环境与职业医学, 2018, 35(5): 400-405. DOI: 10.13213/j.cnki.jeom.2018.17585
LIU Yan-li, ZHANG Hong-jie, ZHANG Hui-tao, NIU Ying-ying, FU Ye, YANG Jin. Role of aryl hydrocarbon receptor expression in oxidative DNA damage induced by polycyclic aromatic hydrocarbons in coke oven workers[J]. Journal of Environmental and Occupational Medicine, 2018, 35(5): 400-405. DOI: 10.13213/j.cnki.jeom.2018.17585
Citation: LIU Yan-li, ZHANG Hong-jie, ZHANG Hui-tao, NIU Ying-ying, FU Ye, YANG Jin. Role of aryl hydrocarbon receptor expression in oxidative DNA damage induced by polycyclic aromatic hydrocarbons in coke oven workers[J]. Journal of Environmental and Occupational Medicine, 2018, 35(5): 400-405. DOI: 10.13213/j.cnki.jeom.2018.17585

芳烃受体表达在焦炉工多环芳烃暴露致DNA氧化损伤中的作用

Role of aryl hydrocarbon receptor expression in oxidative DNA damage induced by polycyclic aromatic hydrocarbons in coke oven workers

  • 摘要: 目的 探讨芳烃受体(AhR)基因表达在焦炉工多环芳烃(PAH)暴露致DNA氧化损伤中的作用。

    方法 选择某钢铁厂焦炉工312人为研究对象,问卷调查工人的基本信息,并采集其血液和尿液。以尿中PAH代谢物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)作为PAH暴露的生物标志物,8-羟基脱氧鸟苷(8-OHdG)作为DNA氧化损伤的指标,采用高效液相色谱法检测2-NAP、2-FLU、9-PHE、1-OHP和8-OHdG的水平。逆转录PCR法测定血液AhR的表达量。

    结果 根据尿中1-OHP的水平(< P25P25~P75,>P75)将工人分为低、中、高暴露组,随着尿中1-OHP水平的升高,2-FLU和9-PHE的水平也逐渐升高。logistic回归显示,校正了性别、年龄、吸烟、饮酒、2-NAP、2-FLU和9-PHE等因素后,尿中1-OHP水平与AhR表达量、8-OHdG水平相关,OR值分别为2.08(95%CI:1.21~3.58)、2.98(95%CI:1.65~5.32),尿中1-OHP水平与AhR表达量和8-OHdG水平均呈线性剂量反应关系(P趋势 < 0.05);尿中8-OHdG水平与AhR表达量相关,OR值为2.18(95%CI:1.35~3.51),并且AhR表达与8-OHdG水平呈线性剂量反应关系(P趋势=0.001)。中介效应分析结果显示:a、b、cc'4个回归系数(分别为1.59、0.32、0.36和1.61)的检验均具有统计学意义(P < 0.05),其中cc'均有意义,说明存在中介效应和直接效应;abc'同号,则说明是部分中介效应。可以认为AhR表达在PAH致DNA氧化损伤作用中起到中介作用,且为部分中介效应。

    结论 PAH暴露、AhR表达与DNA氧化损伤之间具有线性剂量反应关系,并且PAH可能通过影响AhR表达引起DNA的氧化损伤。

     

    Abstract: Objective To study the role of aryl hydrocarbon receptor (AhR) gene expression in oxidative DNA damage induced by polycyclic aromatic hydrocarbons (PAH) in coke oven workers.

    Methods A total of 312 coke oven workers from a steel plant were selected to complete a questionnaire survey on general information and have blood and urine samples collected. Urinary concentrations of four PAH metabolites (PAH biomarkers), including 2-hydroxynaphthalene (2-NAP), 2-hydroxyfluorene (2-FLU), 9-phenanthrol (9-PHE), and 1-pyrenol (1-OHP), and 8-hydroxydeoxyguanosine (8-OHdG, DNA oxidative damage indicator) were determined by high performance liquid chromatography; AhR expression was measured by reverse transcription PCR.

    Results The workers were divided into low, medium, and high exposure groups according to urinary 1-OHP level (< P25, P25-P75, and >P75). With the increasing of 1-OHP level, the levels of 2-FLU and 9-PHE increased. The multiple logistic regression analysis results showed that urinary 1-OHP level was associated with AhR expression (OR=2.08, 95%CI:1.21-3.58) and 8-OHdG level (OR=2.98, 95%CI:1.65-5.32) after adjusted for sex, age, smoking, drinking, 2-NAP, 2-FLU, and 9-PHE in a liner dose-response relationship (Ptrend < 0.05). In addition, AhR expression was positively related to 8-OHdG level (OR=2.18, 95%CI:1.35-3.51) in a linear dose-response relationship (Ptrend=0.001). The mediation analysis results found the regression coefficients of a, b, c, and c' (1.59, 0.32, 0.36 and 1.61, respectively) were of statistical significance (P < 0.05). Specifically, c and c' were both significant, indicating mediation effect and direct effect; ab had a same sign with c' indicating partial mediation effect. So AhR expression played a partial mediation effect in PAH-related oxidative DNA damage.

    Conclusion There are linear dose-response relationships of PAH exposure with AhR expression and oxidative DNA damage, and the effect of PAH exposure on DNA oxidative damage may be mediated by AhR expression.

     

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