低浓度苯接触工人线粒体DNA拷贝数的追踪研究

Follow-up study on mitochondrial DNA copy number in workers exposed to low concentration benzene in China

目的探索低浓度苯接触工人线粒体DNA拷贝数的变化及其影响因素。方法选择上海某化工厂150名低浓度苯接触工人作为2018、2019年连续两年的追踪研究对象,采用问卷调查收集研究对象一般情况,采用实时荧光定量PCR法检测外周血相对线粒体DNA拷贝数并作为氧化应激的检测指标,利用重复测量分析以及广义估计模型分析两年间苯接触工人线粒体DNA拷贝数情况的变化,并探讨其与作业环境中苯接触的关系。结果研究对象在追踪期间的苯接触浓度中位数为0.46 mg/m^3,第25百分位数为0.14 mg/m^3,第75百分位数为0.49 mg/m^3。2018年苯接触工人相对线粒体DNA拷贝数为5.79±0.84,2019年工人相对线粒体DNA拷贝数显著降低,为(4.66±0.58),差异有统计学意义(P<0.01)。重复测量方差分析结果显示:不同接触浓度工人相对线粒体DNA拷贝数差异有统计学意义(P<0.05);不同时间观察的线粒体DNA拷贝数不全相同,差异有统计学意义(P<0.05)。广义估计模型分析结果显示:与高接触浓度组相比,中接触浓度组工人相对线粒体DNA拷贝数降低了0.25(P<0.05)。未发现工龄、年龄、吸烟和饮酒对相对线粒体DNA拷贝数的影响。结论在低于我国现行职业卫生标准的情况下,接触低浓度苯的作业工人仍可出现相对线粒体DNA拷贝数的改变,提示职业性苯接触可能导致线粒体损伤以及氧化应激的产生。

Objective To explore the changes of the mitochondrial DNA copy number in workers exposed to low concentration benzene and the factors associated with such change.Methods A total of 150 workers exposed to low concentration of benzene in a chemical plant in Shanghai were studied,and the mitochondrial DNA copy number for the indicators of oxidative stress were measured twice in a follow-up study during year 2018 and 2019.The repeated measurement analysis and generalized estimation model were used to investigate the changes of the mitochondrial DNA copy number and the relationship between the mitochondrial DNA copy number and low concentration of benzene exposure in the working environment.Results The median of benzene exposure concentration level of the workers was 0.46 mg/m^3,the 25 th percentile was 0.14 mg/m^3,and the 75 th percentile was 0.50 mg/m^3.Compared with the relative mitochondrial DNA copy number of workers exposed to benzene in 2018(5.79±0.84),the relative mitochondrial DNA copy number in 2019(4.66±0.58)was significantly lower(P<0.01).The results of repeated measurement ANOVA showed that the relative mitochondrial DNA copy number of workers with different exposure concentrations was significantly different(P<0.05);the mitochondrial DNA copy number observed at these two years was not the same,and the difference was statistically significant(P<0.05).The results of generalized estimation model analysis showed that compared with high exposure group,the relative mitochondrial DNA copy number of workers exposed to medium concentration group decreased by 0.25(P<0.05).No effect of employment time in this plant,age,smoking and drinking habits on relative mitochondrial DNA copy number was found.Conclusions In the workplaces with the concentration of benzene lower than the current occupational exposure limits in China,it can still observed the change of the relative copy number of mitochondrial DNA among these workers,suggesting that low occupational benzene exposure may lead to oxidative stress and mitochondrial damage,and its mechanism needs further study.