Dataset Information

Plasma microRNA expression and micronuclei frequency in workers exposed to polycyclic aromatic hydrocarbons.

ABSTRACT: 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.We sought to identify PAH-associated miRNAs and evaluate their associations with MN frequency.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.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).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.

SUBMITTER: Deng Q

PROVIDER: S-EPMC4080537 | biostudies-literature | 2014 Jul

REPOSITORIES: biostudies-literature

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Plasma microRNA expression and micronuclei frequency in workers exposed to polycyclic aromatic hydrocarbons.

Deng Qifei Q Huang Suli S Zhang Xiao X Zhang Wangzhen W Feng Jing J Wang Tian T Hu Die D Guan Lei L Li Jun J Dai Xiayun X Deng Huaxin H Zhang Xiaomin X Wu Tangchun T

Environmental health perspectives 20140314 7

<h4>Background</h4>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.<h4>Objectives</h4>We sought to identify PAH-associated miRNAs and evaluate their associations with MN frequency.<h4>Methods</h4>We performed a two-stage study in h ...[more]

PMID: 24633190

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Project description:This study aims to examine global gene expression profiles before and after the work-shift among coke-oven workers (COW). COW work six consecutive days and then take two days off. Two blood and urine samples in each worker were collected before starting to work after two-days off and end-of-shift in the sixth-day work in 2009. Altered gene expressions (ratio of gene expression levels between end-of-shift and pre-shift work) were performed by Human OneArray expression system which probes ~30,000-transcription expression profiling of human genes. Sixteen workers, all men, were enrolled in this study. Median urinary 1-hydroxypyrene (1OHP) levels (mole/mole creatinine) in end-of-shift work were significantly higher than those in pre-shift work (2.58 vs. 0.29, p = 0.0002). Among the 20,341 genes which passed experimental quality control, 26 gene expression changes, 7 positively- and 19 negatively-, were highly correlated with across-the-shift urinary 1OHP levels (end-of-shift – pre-shift 1OHP) (p-value < 0.001). The high and low exposure groups of across-the-shift urinary 1OHP levels dichotomized in ~2.00 µmole/mole creatinine were able to be distinguished by these 26 genes. Some of them are known to be involved in apoptosis, chromosome stability/DNA repair, cell cycle control/tumor suppressor, cell adhesion, development/spermatogenesis, immune function, and neuronal cell function. Sixteen coke-oven workers who had worked in one of two coke-oven plants for at least one year in the largest steel company in Taiwan voluntarily participated in this study between July-October, 2009. Coke-oven workers regularly work 6 days and take two days off. Thus, we collected their blood and urine samples at two different time points: one was during the pre-shift work on the first day after two days off, and the second one was at the end-of-shift work on the 6th work day. Information about age and smoking status was also collected before the collection of biological specimens.

Dataset Information

Plasma microRNA expression and micronuclei frequency in workers exposed to polycyclic aromatic hydrocarbons.

Publications

Plasma microRNA expression and micronuclei frequency in workers exposed to polycyclic aromatic hydrocarbons.

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