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

作　　者：刘艳丽 张红杰 张慧涛 牛莹莹 傅晔 杨瑾 LIU Yan-li;ZHANG Hong-jie;ZHANG Hui-tao;NIU Ying-ying;FU Ye;YANG Jin(Department of Occupational Health, School of Public Health, Shanxi Medical University, Taiyuan, Shanxi 030001, China)

机构地区：[1]山西医科大学公共卫生学院劳动卫生学教研室,山西太原030001

出　　处：《环境与职业医学》2018年第5期400-405,共6页Journal of Environmental and Occupational Medicine

基　　金：山西省自然科学基金项目(编号:201701D121146);国家自然科学基金项目(编号:81273041)

摘　　要：[目的]探讨芳烃受体(Ah R)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-OHd G)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-OHd G的水平。逆转录PCR法测定血液Ah R的表达量。[结果]根据尿中1-OHP的水平(<P25,P25~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Ah R表达量、8-OHd G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Ah R表达量和8-OHd G水平均呈线性剂量反应关系(P趋势<0.05);尿中8-OHd G水平与Ah R表达量相关,OR值为2.18(95%CI:1.35~3.51),并且Ah R表达与8-OHd G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、c和c’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c和c’均有意义,说明存在中介效应和直接效应;ab与c’同号,则说明是部分中介效应。可以认为Ah R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、Ah R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Ah R表达引起DNA的氧化损伤。[Objective] To study the role of aryl hydrocarbon receptor（Ah R） 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;Ah R 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 Ah R 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（P trend〈0.05）.In addition,Ah R expression was positively related to 8-OHdG level（OR=2.18,95%CI：1.35-3.51） in a linear dose-response relationship（P trend=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 Ah R expression played a partial mediation effect in PAH-related oxidative DNA damage.[Conclusion] There are linear dose-response relationships of PAH exposure with Ah R expression and oxidative DNA damage,and the effect of PAH exposure on DNA oxidative damage may be mediated by Ah R expression

关 键 词：多环芳烃 芳烃受体 氧化损伤 1-羟基芘 8-羟基脱氧鸟苷 

分 类 号：R134[医药卫生—劳动卫生]