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外周血线粒体 DNA 拷贝数减少与焦炉工人多环芳烃暴露有关:贝叶斯核机器回归。

Reduction of mitochondrial DNA copy number in peripheral blood is related to polycyclic aromatic hydrocarbons exposure in coke oven workers: Bayesian kernel machine regression.

机构信息

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

Hong Kong Institutes of Diabetes and Obesity, The Chinese University of Hong Kong, Taiyuan, 030001, Shanxi, China.

出版信息

Environ Pollut. 2020 May;260:114026. doi: 10.1016/j.envpol.2020.114026. Epub 2020 Jan 22.

Abstract

Although association between polycyclic aromatic hydrocarbons (PAHs) exposure and mitochondrial DNA copy number (mtDNAcn) was researched by traditional linear model extensively, most of these studies analyzed independent effect of each PAHs metabolite and adjust for the confounding other metabolites concomitantly, without considering others interactions. As a complex organic pollutant, a reasonable statistical method is needed to study toxic effects of PAHs. Therefore, we aimed to conduct a novel statistical approach, Bayesian Kernel Machine Regression (BKMR), to explore the effect of PAHs exposure on mtDNAcn among coke oven workers. In this cross-sectional study, the concentrations urinary of PAHs metabolites were measured using high performance liquid chromatography mass spectrometry (HPLC-MS). The mtDNAcn was measured using real-time quantitative polymerase chain reaction (RT-PCR) in peripheral blood of 696 Chinese coke oven workers. The relationship of urinary of PAHs metabolites and mtDNAcn were evaluated by BKMR model. And the results showed a significant negative effect of PAHs metabolites on mtDNAcn when PAHs metabolites concentrations were all above 35th percentile compared to the median and the statistically significant negative single-exposure effect of 2-OHNAP and 2-OHPHE on mtDNAcn when all of the other PAHs are fixed at a particular threshold (25th, 50th, 75th percentile). The changes in log 2-OHNAP and 2-OHPHE from the 25th to the 75th percentile when other PAHs metabolites were at the 50th percentile were associated with change in mtDNAcn of -0.082 (-0.021, -0.124) and -0.048 (-0.021, -0.090) respectively. And evidence of a linear effect of urinary 2-OHNAP and 2-OHPHE were found. Finally, our findings suggested that PAHs cumulative exposures and particularly single-exposure of 2-OHNAP and 2-OHPHE might compromise mitochondrial function by decreasing mtDNAcn in Chinese coke oven workers.

摘要

虽然多环芳烃 (PAHs) 暴露与线粒体 DNA 拷贝数 (mtDNAcn) 之间的关联已被传统的线性模型广泛研究,但这些研究大多分析了每种 PAHs 代谢物的独立影响,并同时调整了其他代谢物的混杂因素,而没有考虑到其他相互作用。作为一种复杂的有机污染物,需要一种合理的统计方法来研究 PAHs 的毒性作用。因此,我们旨在采用一种新的统计方法,贝叶斯核机器回归 (BKMR),来研究焦炉工人 PAHs 暴露对 mtDNAcn 的影响。在这项横断面研究中,采用高效液相色谱-质谱联用 (HPLC-MS) 法测定尿中 PAHs 代谢物的浓度。采用实时定量聚合酶链反应 (RT-PCR) 法测定 696 名中国焦炉工人外周血 mtDNAcn。采用 BKMR 模型评价尿中 PAHs 代谢物与 mtDNAcn 的关系。结果显示,与中位数相比,当所有 PAHs 代谢物浓度均高于第 35 百分位数时,PAHs 代谢物对 mtDNAcn 有显著的负效应;当所有其他 PAHs 固定在特定阈值(第 25、50、75 百分位数)时,2-OHNAP 和 2-OHPHE 对 mtDNAcn 的单一暴露效应具有统计学意义的负效应。当其他 PAHs 代谢物处于第 50 百分位数时,log2-OHNAP 和 2-OHPHE 从第 25 百分位到第 75 百分位的变化与 mtDNAcn 的变化相关,分别为-0.082(-0.021,-0.124)和-0.048(-0.021,-0.090)。并且发现尿中 2-OHNAP 和 2-OHPHE 有线性效应。最后,我们的研究结果表明,在中国焦炉工人中,PAHs 累积暴露,特别是 2-OHNAP 和 2-OHPHE 的单一暴露,可能通过降低 mtDNAcn 来损害线粒体功能。

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