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Co-exposure to metals and polycyclic aromatic hydrocarbons, microRNA expression, and early health damage in coke oven workers
Abstract Background All humans are now co-exposed to multiple toxic chemicals, among which metals and polycyclic aromatic hydrocarbons (PAHs) are of special concern as they are often present at high levels in various human environments. They can also induce similar early health damage, such as genetic damage, oxidative stress, and heart rate variability (HRV). Exposure to metals, PAHs, and their combined pollutants can alter microRNA (miRNA) expression patterns. Objectives To explore the associations of metal-PAH co-exposure with miRNA expression, and of the associated miRNAs with early health damage. Methods We enrolled 360 healthy male coke oven workers and quantified their exposure levels of metals and PAHs by urinary metals, urinary monohydroxy-PAHs (OH-PAHs), and plasma benzo[a]pyrene-r-7,t-8,t-9,c-10-tetrahydotetrol-albumin (BPDE-Alb) adducts, respectively. We selected and measured ten miRNAs: let-7b-5p, miR-126-3p, miR-142-5p, miR-150-5p, miR-16-5p, miR-24-3p, miR-27a-3p, miR-28-5p, miR-320b, and miR-451a. For miRNAs influenced by the effect modification of metals or PAHs and/or metal-PAH interactions, we further evaluated their associations with biomarkers for genetic damage, oxidative stress, and HRV. Results After adjusting for PAHs and other metals, miRNA expression was found to be negatively associated with aluminum, antimony, lead, and titanium, and positively associated with molybdenum and tin (p < 0.05). Antimony showed modifying effects on the PAH-miRNA associations, while OH-PAHs and BPDE-Alb adducts modified the associations of metals with miRNAs (p for modifying effect < 0.05). Furthermore, miRNA expression was influenced by the antagonistic interactions between antimony and OH-PAHs, and by the synergistical interactions between metals and BPDE-Alb adducts (p interaction < 0.05). Let-7b-5p, miR-126-3p, miR-16-5p, and miR-320b were additionally found to be associated with increased genetic damage in the present study [false discovery rate (FDR)-adjusted p < 0.05]. Conclusions Associations of metal-PAH co-exposure with miRNA expression, and of associated miRNAs with early health damage, suggested potential mechanistic connections between the complex metal-PAH interactions and their deleterious effects that are worthy of further investigation.
Highlights Metals, such as antimony and titanium, were associated with miRNA expression. Metal-miRNA associations were modified by PAH exposure levels, and vice versa. Metals, especially antimony, interacted with PAHs to influence miRNA expression. MiRNAs affected by metal-PAH co-exposure were associated with early health damage.
Co-exposure to metals and polycyclic aromatic hydrocarbons, microRNA expression, and early health damage in coke oven workers
Abstract Background All humans are now co-exposed to multiple toxic chemicals, among which metals and polycyclic aromatic hydrocarbons (PAHs) are of special concern as they are often present at high levels in various human environments. They can also induce similar early health damage, such as genetic damage, oxidative stress, and heart rate variability (HRV). Exposure to metals, PAHs, and their combined pollutants can alter microRNA (miRNA) expression patterns. Objectives To explore the associations of metal-PAH co-exposure with miRNA expression, and of the associated miRNAs with early health damage. Methods We enrolled 360 healthy male coke oven workers and quantified their exposure levels of metals and PAHs by urinary metals, urinary monohydroxy-PAHs (OH-PAHs), and plasma benzo[a]pyrene-r-7,t-8,t-9,c-10-tetrahydotetrol-albumin (BPDE-Alb) adducts, respectively. We selected and measured ten miRNAs: let-7b-5p, miR-126-3p, miR-142-5p, miR-150-5p, miR-16-5p, miR-24-3p, miR-27a-3p, miR-28-5p, miR-320b, and miR-451a. For miRNAs influenced by the effect modification of metals or PAHs and/or metal-PAH interactions, we further evaluated their associations with biomarkers for genetic damage, oxidative stress, and HRV. Results After adjusting for PAHs and other metals, miRNA expression was found to be negatively associated with aluminum, antimony, lead, and titanium, and positively associated with molybdenum and tin (p < 0.05). Antimony showed modifying effects on the PAH-miRNA associations, while OH-PAHs and BPDE-Alb adducts modified the associations of metals with miRNAs (p for modifying effect < 0.05). Furthermore, miRNA expression was influenced by the antagonistic interactions between antimony and OH-PAHs, and by the synergistical interactions between metals and BPDE-Alb adducts (p interaction < 0.05). Let-7b-5p, miR-126-3p, miR-16-5p, and miR-320b were additionally found to be associated with increased genetic damage in the present study [false discovery rate (FDR)-adjusted p < 0.05]. Conclusions Associations of metal-PAH co-exposure with miRNA expression, and of associated miRNAs with early health damage, suggested potential mechanistic connections between the complex metal-PAH interactions and their deleterious effects that are worthy of further investigation.
Highlights Metals, such as antimony and titanium, were associated with miRNA expression. Metal-miRNA associations were modified by PAH exposure levels, and vice versa. Metals, especially antimony, interacted with PAHs to influence miRNA expression. MiRNAs affected by metal-PAH co-exposure were associated with early health damage.
Co-exposure to metals and polycyclic aromatic hydrocarbons, microRNA expression, and early health damage in coke oven workers
Deng, Qifei (author) / Dai, Xiayun (author) / Feng, Wei (author) / Huang, Suli (author) / Yuan, Yu (author) / Xiao, Yongmei (author) / Zhang, Zhaorui (author) / Deng, Na (author) / Deng, Huaxin (author) / Zhang, Xiao (author)
Environmental International ; 122 ; 369-380
2018-11-21
12 pages
Article (Journal)
Electronic Resource
English
PAHs , polycyclic aromatic hydrocarbons , PM , particulate matter , ROS , reactive oxygen species , miRNA , microRNA , COE , coke oven emission , EDTA , ethylenediaminetetraacetic acid , OH-PAH , monohydroxy-PAH , OH-Nap , hydroxynaphthalene , OH-Flu , hydroxyfluorene , OH-Phe , hydroxyphenanthrene , 1-OH-Pyr , 1-hydroxypyrene , LOQ , limits of quantification , ∑OH-Nap , the sum of two OH-Nap , ∑OH-Flu , the sum of two OH-Flu , ∑OH-Phe , the sum of five OH-Phe , ∑OH-PAHs , the sum of ten OH-PAHs , BPDE-Alb adducts , benzo[<italic>a</italic>]pyrene-<italic>r</italic>-7,<italic>t</italic>-8,<italic>t</italic>-9,<italic>c</italic>-10-tetrahydotetrol-albumin adducts , ELISA , sandwich enzyme-linked immunosorbent assay , Ct , cycle threshold , OTM , Olive tail moment , tail DNA% , percent DNA in the tail , MN , micronucleus , 8-OH-dG , 8-hydroxydeoxyguanosine , 8-isoPGF2α , 8-isoprostaglandin-F2α , HRV , heart rate variability , SDNN , standard deviation of all normal to normal NN intervals , rMSSD , square root of the mean of squared differences of adjacent NN intervals , LF , low-frequency power , HF , high-frequency power , TP , total power , ln , natural logarithm , BMI , body mass index , ∑metals , the sum of 23 metals , FDR , false discovery rate , LASSO , least absolute shrinkage and selection operator , MSE , mean squared error , β<inf>std</inf> , standardized coefficients , CI , confidence interval , SD , standard deviation , FR , frequency ratio , β<inf>interaction</inf> , regression coefficient of the interaction term , <italic>p</italic> <inf>ME</inf> , <italic>p</italic> values for modifying effect , IARC , International Agency for Research on Cancer , Metals , Polycyclic aromatic hydrocarbons , Co-exposure , microRNAs , Early health damage