Plasma microRNA Expression and Micronuclei Frequency in Workers Exposed to Polycyclic Aromatic Hydrocarbons

Abstract

Background: Ubiquitous polycyclic aromatic hydrocarbons (PAHs) have been shown to alter gene expression patterns and elevate micronuclei (MN) frequency, but the underlying mechanisms are largely unknown. MicroRNAs (miRNAs) are key gene regulators that may be influenced by PAH exposures and mediate their effects on MN frequency.Objectives: We sought to identify PAH-associated miRNAs and evaluate their associations with MN frequency.Methods: We performed a two-stage study in healthy male coke oven workers to identify miRNAs associated with PAH exposures quantified using urinary monohydroxy-PAHs and plasma benzo[a]pyrene-r-7,t-8,c-10-tetrahydrotetrol-albumin (BPDE–Alb) adducts. In the discovery stage, we used Solexa sequencing to test differences in miRNA expression profiles between pooled plasma samples from 20 exposed workers and 20 controls. We then validated associations with eight selected miRNAs in 365 workers. We further evaluated associations between the PAH-associated miRNAs and MN frequency.Results: In the discovery stage, miRNA expression profiles differed between the exposed and control groups, with 68 miRNAs significantly down-regulated [fold change (FC) ≤ –5] and 3 miRNAs mildly up-regulated (+2 ≤ FC < +5) in the exposed group. In the validation analysis, urinary 4-hydroxyphenanthrene and/or plasma BPDE–Alb adducts were associated with lower miR-24-3p, miR-27a-3p, miR-142-5p, and miR-28-5p expression (p < 0.030). Urinary 1-hydroxynaphthalene, 2-hydroxynaphthalene, 2-hydroxyphenanthrene, and the sum of monohydroxy-PAHs were associated with higher miR-150-5p expression (p < 0.030). These miRNAs were associated with higher MN frequency (p < 0.005), with stronger associations in drinkers (pinteraction < 0.015).Conclusions: Associations of PAH exposures with miRNA expression, and of miRNA expression with MN frequency, suggest potential mechanisms of adverse effects of PAHs that are worthy of further investigation.Citation: Deng Q, Huang S, Zhang X, Zhang W, Feng J, Wang T, Hu D, Guan L, Li J, Dai X, Deng H, Zhang X, Wu T. 2014. Plasma microRNA expression and micronuclei frequency in workers exposed to polycyclic aromatic hydrocarbons. Environ Health Perspect 122:719–725; http://dx.doi.org/10.1289/ehp.1307080

Polycyclic Aromatic Hydrocarbons–Associated MicroRNAs and Heart Rate Variability in Coke Oven Workers

“…12 These workers were aged between 20 and 60 years old, working in their current workplaces (ie, at the top, side, bottom, and adjacent workplaces of coke ovens, or in offices) for at least 1 year, without recent medication use in the preceding 3 months or self-reported history of chronic diseases, including cancer, chronic inflammation, hypertension, and the serious medical conditions affecting HRV (heart failure, angina, arrhythmia, myocardial infarction, and other non-classified heart problems). We set up multiple monitors in their workplaces and collected the airborne samples with an average flow rate of 2.0 L/min for 6 h. Measurement for PAH in the collected airborne samples was performed by high-performance liquid chromatography as shown in our previous study.…”

“…Among the 71 PAH-related miRNAs we identified previously, 12 six miRNAs (miR-24-3p, miR-27a-3p, miR-142-5p, miR-320b, miR-150-5p, and miR-126-3p) involved in cardiovascular diseases according to literature review [16][17][18][19][20][21] were chosen in this study to explore their relationships with HRV indices in the validation population (365 coke oven workers) according to our previous study. 12 Four of these miRNAs (miR-24-3p, miR-27a-3p, miR-150-5p, and miR-142-5p) have been detected before. 12 As miRNAs might also interact functionally with environmental factors to affect phenotypes and diseases, 22 we also performed stratification analysis and evaluated the interaction effect between miRNAs and the environmental factors on HRV in this study.…”

“…12 Four of these miRNAs (miR-24-3p, miR-27a-3p, miR-150-5p, and miR-142-5p) have been detected before. 12 As miRNAs might also interact functionally with environmental factors to affect phenotypes and diseases, 22 we also performed stratification analysis and evaluated the interaction effect between miRNAs and the environmental factors on HRV in this study.…”

“…9,10 A previous study also showed modified expression of miRNAs involved in oxidative stress and inflammation in circulating blood leukocytes from electric-steel plant facility workers who were exposed to air particles rich in lead and cadmium. 11 In our previous two-stage study in coke oven workers, 12 we first screened and compared hundreds of miRNAs in two plasma pools of workers with low or high PAH exposure (discovery stage), which ultimately identified 71 differentially expressed miRNAs. In the validation stage with 365 coke oven workers, we further validated and identified five PAH-associated miRNAs showing dose-response relationships with the oxidative stress level of these coke oven workers.…”

Analysis of plasma microRNA expression profiles in a Chinese population occupationally exposed to benzene and in a population with chronic benzene poisoning

“…Simultaneously, growing evidences have indicated that exposure to hazardous environmental factors may significantly disrupt miRNA expression patterns (10)(11)(12). Previous studies also revealed that dysregulated miRNAs are involved in responses to polycyclic aromatic hydrocarbons (PAHs) (13). Further studies suggested that miRNAs and their interactions with environmental factors might affect the effects of PAHs exposure on oxidative DNA damage and lipid peroxidation (14).…”