端粒长度与职业性多环芳烃暴露的关系研究

目的 探讨多环芳烃(PAHs)暴露与端粒长度的关系,以寻找评价多环芳烃致外周血遗传物质损伤的效应性生物标志物.方法 以145名焦炉作业工人(炉顶工30名、炉侧工76名、炉底工39名)作为暴露组,68名医护人员作为对照组,收集其工作周末班6 h后的尿液和1 ml肘静脉血.测定研究对象工作环境空气中苯溶物和颗粒相苯并(a)芘浓度、尿中1-羟基芘(1-OHPyr)水平;应用定量PCR方法测定其外周血全基因组DNA的相对端粒长度(RTL),分析端粒长度与PAHs外暴露水平和相关影响因素的关系.结果 暴露组空气中苯溶物和颗粒相苯并(a)芘浓度的中位数分别为328.6 μg/m3和926.9 ng/m3,均高于对照组区域苯溶物为97.8 μg/m3,颗粒相苯并(a)芘浓度为49.1 ng/m3].暴露组尿1-OHPyr水平(12.2 μmol/mol Cr)高于非暴露组(0.7 μmol/mol Cr),差异有统计学意义(t=26.971,P<0.01).暴露组RTL为1.10 ±0.75,短于非暴露组的1.43±1.06,差异有统计学意义(t=2.263,P=0.026),校正每日吸烟量和尿1-OHPyr水平后的协方差分析也显示差异有统计学意义(F校正=5.496,P校正=0.020).分层分析中发现PAHs暴露对RTL的影响在男性(暴露组:1.08 ±0.73;非暴露组:1.51±1.10;F=9.212,P=0.003)和不饮酒(暴露组:0.96±0.38;非暴露组:1.26±0.46;F=6.484,P=0.012)的工人中更为显著.非暴露组的RTL与年龄呈负相关(r=-0.284,P=0.019).结论 PAHs暴露可对工人外周血全基因组DNA的端粒长度产生影响,这种影响在男性和不饮酒的焦炉工中更为明显,提示端粒长度可能是PAHs暴露致遗传物质损伤的效应生物标志物之一.

Association between telomere length and occupational polycyclic aromatic hydrocarbons exposure

Objective To explore the association between polyeyclic aromatic hydrocarbons (PAHs) exposure and telomere length(TL),so as to investigate the effective biomarkers to evaluate the genetic daolage in peripheral blood of workers exposed to PAHs.Methods The exposure group consisted of 145 coke-oven workers (including 30 top-oven workers,76 side-oven workers and 39 bottom-oven workers),and the non-exposure control group comprised 68 medical staffs.At 6 hours after the weekend duty shift,the samples of urine and 1 ml venous blood were collected from each subject. Airborne benzene-soluble matter (BSM)and particulate-phase B(a)P in the working environment of coke-oven and controls were sampled and analyzed.The concentration of urinary 1-hydroxypyrene(1-OHPyr)was determined.A real-time PCR method was used to determine the relative telomere length(RTL)of genomic DNA in peripheral blood.The relationship between the RTL and external exposure of PAHs,the potential factors which might have influence on TL were analyzed.Results The medians of air BSM and particulate-phase B(a)P were higher in cokeoven(BSM:328.6 μg/m3;B(a)P:926.9 ng/m3)than those in control working environment(BSM:97.8 μg/m3;B(a)P:49.1 ng/m3).The level of 1-OHPyr among coke-oven workers was significantly higher than that of non-exposed group ( 12.2 μmol/mol Cr vs 0. 7 μmol/mol Cr; t = 26. 971, P < 0. 01 ). RTL in coke-oven workers were significantly shorter than those of controls ( 1.10 ±0. 75 vs 1.43 ± 1.06; t =2. 263,P =0. 026) ,and after adjusting for cigarettes per day and urinary 1-OHPyr,the significant difference was still observed ( Fadju = 5.496, Padju = 0. 020). Stratification analysis found that RTL among the male and nondrinking groups in coke-oven workers were shorter than those the same sex and alcohol using status in controls ( 1. 08± 0. 73 vs 1. 51± 1.10, F = 9. 212, P = 0. 003 ; 0. 96 ± 0. 38 vs 1. 26 ± 0.46, F = 6. 484, P =0. 012 ). Significant correlation between RTL and age was found ( r = -0. 284, P =0. 019 ) in non-exposure group. Conclusion PAH-expesure has effect on TL of genomic DNA in peripheral blood,which is mainly observed in the male and non-drinking groups between PAH-exposed workers and controls. It indicates that TL of gcnomic DNA in peripheral blood might be an effective biomarker as PAH-induced genetic damage.