Qifei Deng1, Xiayun Dai2, Wei Feng3, Suli Huang3, Yu Yuan3, Yongmei Xiao4, Zhaorui Zhang4, Na Deng4, Huaxin Deng3, Xiao Zhang3, Dan Kuang3, Xiaohai Li3, Wangzhen Zhang5, Xiaomin Zhang3, Huan Guo3, Tangchun Wu6. 1. Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Faculty of Preventive Medicine, School of Public Health, Sun Yat-sen University, Guangzhou, Guangdong, China. Electronic address: dengqf3@mail.sysu.edu.cn. 2. State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China; Wuhan Prevention and Treatment Center for Occupational Diseases, Wuhan, Hubei, China. 3. State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China. 4. Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Faculty of Preventive Medicine, School of Public Health, Sun Yat-sen University, Guangzhou, Guangdong, China. 5. Institute of Industrial Health, Wuhan Iron and Steel Corporation, Wuhan, Hubei, China. 6. State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China. Electronic address: wut@tjmu.edu.cn.
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 (pinteraction < 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.
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 (pinteraction < 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.
Authors: Caitlin G Howe; Helen B Foley; Shohreh F Farzan; Thomas A Chavez; Mark Johnson; John D Meeker; Theresa M Bastain; Carmen J Marsit; Carrie V Breton Journal: Epigenetics Date: 2021-10-30 Impact factor: 4.861
Authors: Bethany Sanchez; Xixi Zhou; Amy S Gardiner; Guy Herbert; Selita Lucas; Masako Morishita; James G Wagner; Ryan Lewandowski; Jack R Harkema; Chris Shuey; Matthew J Campen; Katherine E Zychowski Journal: Part Fibre Toxicol Date: 2020-07-01 Impact factor: 9.400
Authors: Sara S Nozadi; Li Li; Li Luo; Debra MacKenzie; Esther Erdei; Ruofei Du; Carolyn W Roman; Joseph Hoover; Elena O'Donald; Courtney Burnette; Johnnye Lewis Journal: Int J Environ Res Public Health Date: 2021-12-31 Impact factor: 3.390