邻苯二甲酸酯暴露对多环芳烃与8-羟基-2'-脱氧鸟苷结合的影响。
Effect of exposure to phthalates on association of polycyclic aromatic hydrocarbons with 8-hydroxy-2'-deoxyguanosine.
作者信息
Hou Jian, Yin Wenjun, Li Pei, Huang Yidan, Wan Yanjian, Hu Chen, Xu Tian, Cheng Juan, Wang Lin, Yu Zhiqiang, Yuan Jing
机构信息
Department of Occupational and Environmental Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Hangkong Road 13, Wuhan 430030, Hubei, PR China; Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, and State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Hangkong Road 13, Wuhan 430030, Hubei, PR China.
State Key Laboratory of Organic Geochemistry, Guangdong Key Laboratory of Environment and Resources, Guangzhou Institute of Geochemistry, Chinese Academy of Sciences, Guangzhou 510640, PR China.
出版信息
Sci Total Environ. 2019 Nov 15;691:378-392. doi: 10.1016/j.scitotenv.2019.07.113. Epub 2019 Jul 9.
BACKGROUND
Although polycyclic aromatic hydrocarbons (PAHs) and phthalates separately related to oxidative DNA damage have been reported, the joint effect of them on oxidative DNA damage need to be evaluated.
METHODS
In this pilot study, 106 participants were recruited from the community-dwelling residents (n=1240) of Wuhan city, China. Each individual provided three continuous days of spot urine samples for measuring the urinary monohydroxylated PAHs (OH-PAHs), phthalates metabolites and 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels in the two seasons. Linear mixed effect model and Bayesian Kernel Machine Regression (BKMR) were used to analyze joint effect of urinary PAHs and phthalates metabolites on urinary 8-OHdG levels. We measured cellular and mitochondrial reactive oxygen species (ROS), malondialdehyde (MDA) and glutathione peroxidase (GSH-Px) levels as well as IL-6 and IL-8 secretions by the corresponding commercial kits in HepG2 cells treated with di (2-ethylhexyl) phthalate (DEHP, 62.5, 125.00, 250.00, 500.00 or 1000.00μM) alone, benzo[a]pyrene (BaP, 50.00μM) alone or both DEHP and BaP.
RESULTS
Linear mixed effect model showed that each of urinary PAHs metabolite was positively associated with urinary 8-OHdG levels; urinary level of mono (2-ethylhexyl) phthalate or monoisononyl phthalate was positively associated with urinary 8-OHdG levels; BKMR model indicated that a positive association of eight OH-PAHs with urinary 8-OHdG levels, nine urinary phthalates metabolites enhanced the association. We found that DEHP at the indicated concentration plus 50.00μM BaP increased cellular and mitochondrial ROS levels, IL-6 and IL-8 secretions at 24 and 48h as well as MDA levels and GSH-Px activities at 48h, compared to the solvent control.
CONCLUSIONS
Exposure to certain dose phthalates may attenuate the positive association of PAHs exposure with oxidative DNA damage in the body. DEHP at the certain concentrations enhanced BaP-induced mitochondrial ROS, pro-inflammatory response and the activation of the antioxidant defense system in HepG2 cells.
背景
尽管已有报道多环芳烃（PAHs）和邻苯二甲酸酯分别与氧化性DNA损伤有关，但它们对氧化性DNA损伤的联合作用仍需评估。
方法
在这项初步研究中，从中国武汉市的社区居民（n = 1240）中招募了106名参与者。每位参与者提供连续三天的即时尿样，用于测量两个季节中尿中单羟基化多环芳烃（OH-PAHs）、邻苯二甲酸酯代谢物和8-羟基-2'-脱氧鸟苷（8-OHdG）的水平。采用线性混合效应模型和贝叶斯核机器回归（BKMR）分析尿中多环芳烃和邻苯二甲酸酯代谢物对尿中8-OHdG水平的联合作用。我们使用相应的商业试剂盒测量了用邻苯二甲酸二（2-乙基己基）酯（DEHP，62.5、125.00、250.00、500.00或1000.00μM）、苯并[a]芘（BaP，50.00μM）单独处理或DEHP和BaP共同处理的HepG2细胞中的细胞和线粒体活性氧（ROS）、丙二醛（MDA）和谷胱甘肽过氧化物酶（GSH-Px）水平，以及IL-6和IL-8的分泌。
结果
线性混合效应模型显示，每种尿中多环芳烃代谢物均与尿中8-OHdG水平呈正相关；单（2-乙基己基）邻苯二甲酸酯或单异壬基邻苯二甲酸酯的尿水平与尿中8-OHdG水平呈正相关；BKMR模型表明，八种OH-PAHs与尿中8-OHdG水平呈正相关，九种尿中邻苯二甲酸酯代谢物增强了这种相关性。我们发现，与溶剂对照相比，在指定浓度的DEHP加50.00μM BaP处理下，细胞和线粒体ROS水平、24小时和48小时的IL-6和IL-8分泌以及48小时的MDA水平和GSH-Px活性均增加。
结论
接触一定剂量的邻苯二甲酸酯可能会减弱多环芳烃暴露与体内氧化性DNA损伤之间的正相关。特定浓度的DEHP增强了BaP诱导的HepG2细胞线粒体ROS、促炎反应和抗氧化防御系统的激活。
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