Effect of exposure to phthalates on association of polycyclic aromatic hydrocarbons with 8-hydroxy-2'-deoxyguanosine

Jian Hou; Wenjun Yin; Pei Li; Yidan Huang; Yanjian Wan; Chen Hu; Tian Xu; Juan Cheng; Lin Wang; Zhiqiang Yu; Jing Yuan

doi:10.1016/j.scitotenv.2019.07.113

Effect of exposure to phthalates on association of polycyclic aromatic hydrocarbons with 8-hydroxy-2'-deoxyguanosine

Sci Total Environ. 2019 Nov 15:691:378-392. doi: 10.1016/j.scitotenv.2019.07.113. Epub 2019 Jul 9.

Authors

Jian Hou¹, Wenjun Yin¹, Pei Li², Yidan Huang¹, Yanjian Wan³, Chen Hu¹, Tian Xu¹, Juan Cheng¹, Lin Wang⁴, Zhiqiang Yu⁵, Jing Yuan⁶

Affiliations

¹ 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.
² 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.
³ Wuhan Center for Disease Prevention and Control, Department of Environmental Health and Food Safety, Wuhan 430022, Hubei, PR China.
⁴ 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.
⁵ 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. Electronic address: zhiqiang@gig.ac.cn.
⁶ 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. Electronic address: jyuan@tjh.tjmu.edu.cn.

PMID: 31323583
DOI: 10.1016/j.scitotenv.2019.07.113

Abstract

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.

Keywords: 8-hydroxy-2′-deoxyguanosine; Bayesian kernel machine regression; Phthalates; Polycyclic aromatic hydrocarbons; Reactive oxygen species.