Coke Oven Workers Research Articles

Global H3K79 di-methylation mediates DNA damage response to PAH exposure in Chinese coke oven workers.

Polycyclic aromatic hydrocarbons (PAHs) are the main contaminants of coke oven emissions which can induce serious genetic damage in coke oven workers. Epigenetic alternations play essential roles in the regulation of DNA damage effect of PAHs. Previous studies indicate that H3K79 di-methylation (H3K79me2) is integral in DNA damage repair. However, the potential role of H3K79me2 in DNA damage response (DDR) following PAHs exposure is still unclear. In this study, we recruited 256 male coke oven workers and control workers, and examined H3K79me2 and DNA damage in their peripheral blood lymphocytes (PBLCs). The results showed that global H3K79me2 of coke oven workers was 29.3% less than that of the controls (P<0.001). The H3K79me2 was negatively correlated with the concentration of urinary 1-hydroxypyrene (1-OHP) (β=-0.235, P<0.001) and level of genetic damage evaluated by comet assay (βTail DNA %=-0.313, P<0.001; βOTM=-0.251, P=0.008). Consistently, we found that benzo(a)pyrene (BaP) inhibited H3K79me2 in immortalized human bronchial epithelial (HBE) cells in a time-dependent manner. In order to explore the function of H3K79me2 in PAHs DDR, we established histone 3.1/3.3 K79A mutant cells (H3K79A) to suppress H3K79me2. H3K79A cells showed more serious DNA damage and decreased cell viability than control cells after BaP treatment. In addition, we also found that the expression of DOT1L, the only methyltransferase in H3K79, was repressed by BaP dose-dependently. DOT1L knockdown resulted in decreased H3K79me2 level and aggravated DNA damage after BaP exposure. This suggests that BaP induces H3K79me2 repression via inhibiting DOT1L expression. In conclusion, these findings indicate that PAH exposure decreases the level of global H3K79me2, which is integral for DNA damage response regulation of PAHs.

Benchmark dose estimation for coke oven emissions based on oxidative damage in Chinese exposed workers

Coke oven emissions (COEs) can cause oxidative stress of the body, which in turn induces the occupational lung disease and also increases the risk of other diseases. COEs are the major occupational hazard factors for coke oven workers. The aim of the study is to explore the influences of COEs exposure on oxidative damage and estimate the benchmark dose (BMD) of COEs. A group of 542 workers exposed to COEs and 237 healthy controls from the same city were recruited in this study. The corresponding measuring kits were used to determine the plasma biomarkers of oxidative damage level. Generalized linear models and trend tests were used to analyze the relationship between COEs exposure and biomarkers. EPA Benchmark Dose Software was performed to calculate BMD and the lower confidence limit of the benchmark dose (BMDL) of COEs exposure. The results showed the significant dose-response relationship was observed between COEs exposure and oxidative damage with T-AOC as a biomarker. The BMD of COEs exposure were 2.83 mg/m3 and 1.39 mg/m3 in males and females, respectively, and the corresponding BMDL were 1.47 mg/m3 and 0.75 mg/m3 in males and females, respectively. Our results suggested the exposure level of COEs below the current national occupational exposure limits (OELs) would induce oxidative damage, and the OEL of COEs based on the T-AOC damage was suggested at 0.03 mg/m3 in this study.Keywords: Coke oven emissions, polycyclic aromatic hydrocarbons, oxidative damage, plasma total antioxidant capacity, benchmark dose, occupational exposure limits

Association between H3K36me3 modification and methylation of LINE-1 and MGMT in peripheral blood lymphocytes of PAH-exposed workers.

To explore the epigenetic alterations in response to DNA damage following polycyclic aromatic hydrocarbons (PAHs) exposure and the crosstalk between different epigenetic regulations, we examined trimethylated Lys 36 of histone H3 (H3K36me3) and methylation of 'long interspersed element-1 (LINE-1)' and 'O 6-methylguanine-DNA methyltransferase (MGMT)' in peripheral blood lymphocytes (PBLCs) of 173 coke oven workers (PAH-exposed group) and 94 non-exposed workers (control group). The PAH-exposed group showed higher internal PAH exposure level, enhanced DNA damage and increased MGMT expression (all P<0.001). Notably, the methylation of LINE-1 and MGMT decreased by 3.9 and 40.8%, respectively, while H3K36me3 level was 1.7 times higher in PBLCs of PAH-exposed group compared to control group (all P<0.001). These three epigenetic marks were significantly associated with DNA damage degree (all P<0.001) and PAH exposure level in a dose-response manner (all P<0.001). LINE-1 hypomethylation is correlated with enhanced H3K36me3 modification (β=-0.198, P=0.002), indicating a synergistic effect between histone modification and DNA methylation at the whole genome level. In addition, MGMT expression was positively correlated with H3K36me3 modification (r=0.253, P<0.001), but not negatively correlated with MGMT methylation (r=0.202, P<0.05). The in vitro study using human bronchial epithelial cells treated with the organic extract of coke oven emissions confirmed that H3K36me3 is important for MGMT expression following PAH exposure. In summary, our study indicates that histone modification and DNA methylation might have synergistic effects on DNA damage induced by PAH exposure at the whole genome level and H3K36me3 is more essential for MGMT expression during the course.

Benchmark dose estimation for coke oven emissions based on oxidative damage in Chinese exposed workers

Coke oven emissions (COEs) can cause oxidative stress of the body, which in turn induces the occupational lung disease and also increases the risk of other diseases. COEs are the major occupational hazard factors for coke oven workers. The aim of the study is to explore the influences of COEs exposure on oxidative damage and estimate the benchmark dose (BMD) of COEs. A group of 542 workers exposed to COEs and 237 healthy controls from the same city were recruited in this study. The corresponding measuring kits were used to determine the plasma biomarkers of oxidative damage level. Generalized linear models and trend tests were used to analyze the relationship between COEs exposure and biomarkers. EPA Benchmark Dose Software was performed to calculate BMD and the lower confidence limit of the benchmark dose (BMDL) of COEs exposure. A significant association was observed between COEs exposure and oxidative damage with T-AOC as a biomarker. The BMD of COEs exposure were 2.83 mg/m3 and 1.39 mg/m3 for males and females, respectively, and the corresponding BMDL were 1.47 mg/m3 and 0.75 mg/m3, respectively. Our results suggested that the exposure level of COEs below the current national occupational exposure limits (OELs) would induce oxidative damage, and the OEL of COEs based on the T-AOC damage was suggested at 0.03 mg/m3 in this study.

Telomere Length Alterations in Occupational Toxicants Exposure: An Integrated Review of the Literature

Telomere integrity is critical for chromosomal stability. Evidence is rapidly growing that impaired telomere integrity may explain the higher risk of some diseases among specific occupations. This review aimed to assess the impact of occupational toxicants exposure on telomere length (TL) and to identify each toxicant's mechanism of action based on an integrative review of available evidence. A literature search was carried out using a set of keywords in different databases. Searches were limited to English publications from 2009 to 2019. Only studies that were using blood samples for TL measurements were included. Finally, 22 studies with a total of 5674 participants, were included. These studies included factory workers from various industries, farmers, coke-oven workers, hairdressers, traffic officers, and drivers. The toxicants were grouped into four categories, including persistent organic pollutants (7 articles), aromatic amines (9 articles), heavy metals (3 articles), and fine particulate matter (PM2.5) (3 articles). Different effects of the same toxicant in TL were observed in various occupations. Factors such as biological characteristics of exposed individuals (especially gene variations and age), diet, lifestyle, dose, and duration of exposure might have modulatory effects on mechanisms and extent of influences of toxicants on TL. Further possible modes of actions affecting the TL are oxidative stress, telomerase expression, systemic inflammation, epigenetic modification, and genotoxicity. In conclusion, various toxicants affect TL differently, but the effect may be moderated by improving the workers’ lifestyle. The involvement of different interrelated pathways may explain the differences in TL alterations.

Association of Urinary Phenol Concentration and Blood Biochemical Indices in Coke Oven Workers

Objective: To explore the association of urinary phenol concentration and blood biochemical indices in coke oven workers. Methods: From April to may 2019, we investigated 771 employing coke oven workers from a coke plant in Taiyuan city, and categorized into benzene-exposed group (n=402) and control group (n=369) based on their benzene exposures in workplace and urophenol concentrations. All subjects were interviewed face-to-face using a questionnaire including name, age (year) , gender, smoking and drinking habits, personal vocational history, working length (year) , and occupational protection, etc. Post-shift urine samples detected using a gas chromatography-hydrogen flame ionization detector. Fasting venous blood was drawn in the morning and centrifuged, the separated serum were detected the following items using an automatic blood biochemistry analyzer. Covariance and multiple linear regression were used to test the association of urinary phenol concentration and the levels of all the blood biochemical indices. Results: The subjects were predominantly males (n=719, 93.3%) , with an average age of (42.3±8.2) years and an average working length of (20.6±8.2) years. Compared with the control group, the benzene-exposed group were significantly different in age, working length of years, gender, smoking and drinking habits (P<0.05) . The median (interquartile interval) concentration of urinary phenol was 6.00 (0.00-33.00) μg/ml in the benzene-exposed group, which was significantly higher than that in the control group (P<0.05) . Covariance analysis indicated that the fasting blood glucose, total cholesterol and high density cholesterol in the benzene-exposed group were significantly reduced compared with the control group, yet the serum creatinine, serum uric acid and triglyceride were significantly increased (P<0.05) . Multiple linear regression showed that, an increase of each natural logarithm (Ln) transformed urinary phenol concentration was significantly associated with increases in serum uric acid level [9.82 (95%CI: 2.18-17.47) μmol/L] and cholesterol level[0.10 (95%CI:0.00-0.20) mmol/L]. An increase of each Ln-transformed accumulated benzene exposure levels was significantly associated with an increase in total cholesterol level[0.09 (95%CI: 0.01-0.17) mmol/L]. Conclusion: Occupational benzene exposure is possibly related to the variation of purine and total cholesterol metabolism in coke oven workers.

Mediation of the association between polycyclic aromatic hydrocarbons exposure and telomere attrition by oxidative stress: A prospective cohort study

Previous studies have reported associations between polycyclic aromatic hydrocarbons (PAHs) exposure and telomere attrition, but the underlying mechanisms remain to be elucidated. This study aimed to explore the mediation role of oxidative stress on the effects of PAHs exposure on telomere attrition in a cohort study of 1180 coke-oven workers. We determined baseline urinary concentrations of ten urinary PAH metabolites, two oxidative stress biomarkers [8-hydroxydeoxyguanosine (8-OHdG) and 8-iso-prostaglandin-F2α (8-isoPGF2α)] and peripheral leukocytes telomere length (TL) in both baseline and follow-up visits. Mediation analysis was applied to assess effects of oxidative stress biomarkers on the PAHs-TL attrition associations. The baseline 8-OHdG had a significant dose-response relationship with TL decline [β(95 %CI) = 0.07(0.03−0.12), P = 0.001] and TL ratio [β(95 %CI)]=0.07 (0.02−0.12), P = 0.003]. Mediation analyses indicated that 8-OHdG mediated a separate 39.1 %, 47.0 %, 43.3 %, and 58.0 % of the associations between 1-hydroxynaphthalene (1-OHNa), 2-OHNa, ΣOHNa, 1-hydroxypyrene (1-OHP) and TL decline (P = 0.016, 0.008, 0.012, and 0.014, respectively). Additionally, 8-OHdG mediated a separate 44.8 %, 49.4 %, 49.2 %, and 35.5 % of the associations between 1-OHNa, 2-OHNa, ΣOHNa, 1-OHP and TL ratio (P = 0.012, 0.008, 0.012, and 0.046, respectively). Our study proposed the positive association of 8-OHdG with TL attrition and revealed the mediation roles of 8-OHdG in PAHs-TL attrition associations.

Lead exposure and its interactions with oxidative stress polymorphisms on lung function impairment: Results from a longitudinal population-based study

Exposure to lead (Pb) and cadmium (Cd) were related to lung function impairment, and this association may be modified by genetic variants in oxidative stress response. Here we enrolled 1243 coke-oven workers in a prospective cohort who were followed up from 2010 to 2014, assessed the associations of Pb and Cd exposure with 4-year lung function impairment, and further explored the interaction effects of Pb with 2664 single nucleotide polymorphisms (SNPs) in 345 oxidative stress related genes. Urinary levels of Pb, Cd, and two oxidative stress biomarkers [8-iso-prostaglandin F2α (8-iso-PGF2α) for lipid peroxidation and 8-hydroxy-2′-deoxyguanosine (8-OHdG) for oxidative DNA damage] were measured at baseline only and their lung function levels were measured both at baseline and at the end of follow-up. Each 10-fold increase in urinary Pb was associated with −159 (95%CI: −254, −64.2) mL and −3.63% (95%CI: −6.48%, −0.78%) changes in FEV1 and percent predicted FEV1 (ppFEV1), respectively. But none significant associations were observed for Cd. NQO1 rs2917670 showed significant interaction with Pb on elevated FEV1 decline after multiple comparison (Pint=1.54 × 10−5). In addition, urinary Pb increased with 8-iso-PGF2α and the rs2917670-C could significantly decrease NQO1 expression in normal lung tissues. These findings suggested the gene-environmental interaction of NQO1 rs2917670 and Pb exposure on the reduction of FEV1. The effect of Pb exposure on elevated oxidative stress and the decreased expression of antioxidant enzyme NQO1 caused by rs2917670-C allele may partly explain the underlying biological mechanism.

Environmental Monitoring of PAHs Exposure, Biomarkers and Vital Status in Coke Oven Workers.

A follow-up study of a cohort of workers from a coke plant compared with a control group from the same industrial area was conducted in 2019. The recruitment and environmental and biomarker measurements were performed during 1993/1994. The environmental concentrations of polycyclic aromatic hydrocarbons (PAH), B(a)P, pyrene and nitro-PAH were measured. Personal data were collected via an individual semi-structured questionnaire by a trained physician. All biomarkers were measured after a specific blood drawing for every test. Significant risks (ORs) were observed for nitro-PAH (≥0.12 µg/m3) [OR = 7.96 (1.01–62.82)], urinary 1-hydroxypyrene (1-OHpy) (≥0.99 µmoles/moles of creatinine) [OR = 11.71 (1.47–92.90)], PAH DNA adducts (P32) (≥2.69 adducts/108 nucleotides) [OR = 5.46 (1.17–25.58)], total nitro-PAH hemoglobin adducts (≥161.68 fg/µg of Hb) [OR = 5.92 (1.26–27.86)], sister chromatid exchange (SCE) with TCR (≥377.84 SCE/cell chromosomes) [OR = 13.06 (3.95–93.10)], sister chromatid exchange with T (≥394.72 total SCE) [OR = 13.06 (3.95–93.10)], and sister chromatid exchange with X (≥8.19 mean SCE) [OR = 13.06 (3.95–93.10)]. Significant risk of death for all causes and chromosomal aberrations (48 h) (OR = 7.19 [1.19–43.44]) or micronuclei in culture at 48 h (OR = 3.86 [1.04–14.38]) were also found.

Urinary Mercapturic Acids to Assess Exposure to Benzene and Other Volatile Organic Compounds in Coke Oven Workers.

Coke production was classified as carcinogenic to humans by the International Agency for Research on Cancer. Besides polycyclic aromatic hydrocarbons, coke oven workers may be exposed to benzene and other volatile organic compounds (VOCs). The aim of this study was to assess the exposure to several VOCs in 49 coke oven workers and 49 individuals living in the same area by determining urinary mercapturic acids. Active tobacco smoking was an exclusion criterion for both groups. Mercapturic acids were investigated by a validated isotopic dilution LC-MS/MS method. Linear models were built to correct for different confounding variables. Urinary levels of N-acetyl-S-phenyl-L-cysteine (SPMA) (metabolite of benzene), N-acetyl-S-(2-hydroxy-1/2-phenylethyl)-L-cysteine (PHEMA) (metabolite of styrene), N-acetyl-S-(2-cyanoethyl)-L-cysteine (CEMA) (metabolite of acrylonitrile), N-acetyl-S-[1-(hydroxymethyl)-2-propen-1-yl)-L-cysteine and N-acetyl-S-(2-hydroxy-3-buten-1-yl)-L-cysteine (MHBMA) (metabolites of 1,3-butadiene) were 2–10 fold higher in workers than in controls (p < 0.05). For SPMA, in particular, median levels were 0.02 and 0.31 µg/g creatinine in workers and controls, respectively. Among workers, coke makers were more exposed to PHEMA and SPMA than foremen and engine operators. The comparison with biological limit values shows that the exposure of workers was within 20% of the limit values for all biomarkers, moreover three subjects exceeded the restrictive occupational limit value recently proposed by the European Chemicals Agency (ECHA) for SPMA.

TH1/TH2 type cytokine expression and DNA aberrant methylation analysis in peripheral blood of coke oven workers

To understand the exposure levels of polycyclic aromatic hydrocarbons(PAHs) and the expression of interleukin-2(IL-2), interferon-γ(IFN-γ), interleukin-4(IL-4), interleukin-10(IL-10) in peripheral blood of coke oven workers exposed to coke oven emissions(COEs). The other purpose of this study was to understand the performance of IFN-γ and IL-10 epigenetic mechanisms in COEs exposure damage. The 85 workers exposed to COEs in a coking plant were randomly selected as the exposure group. The 47 workers who were exposed to non-COEs in the coking plant were used as the control group. The morning urine of the exposure group and the control group were subjected to detection of 1-OHPyr levels with alkaline hydrolysis High-performance liquid chromatography fluorescence, urine creatinine correction. The peripheral venous blood were subjected to detection of the expression of IL-2, IFN-γ, IL-4 and IL-10 with enzyme-linked immunosorbent assay. And methylation levels of IFN-γ and IL-10 were analyzed by time of flight mass spectrometry. The urine 1-hyroxy-pyrene(1-OHPyr) content of coke oven workers was higher than that of the control group(F=12. 446, P&lt;0. 05). The urine 1-OHPyr content of the furnace side and the furnace top were higher than the control group, and the differences were statistically significant. Compared with the control group, serum IL-2 content of coke oven workers decreased(F=14. 774, P&lt;0. 05), and serum IFN-γ content of coke oven workers decreased(F=46. 379, P&lt;0. 05), the serum IL-4 content of coke oven workers increased(F=17. 426, P&lt;0. 05), the serum IL-10 content of coke oven workers increased(F=33. 515, P&lt;0. 05), and the TH1/TH2 ratio of coke oven workers decreased(F=21. 677, P&lt;0. 05). In the exposed group, the level of IFN-γ in the top of the furnace was higher than that in the bottom of the furnace. The difference was statistically significant. The level of IL-10 in the top and bottom of the furnace was lower than that in the furnace. The difference was statistically significant. The IL-10 CpG-11, CpG-15 and mean methylation rates in the exposed group were lower than those in the control group, and the differences were statistically significant. The methylation rate of IFN-γ CpG-5 in the exposed group was higher than that in the control group, and the difference was statistically significant. The urine 1-OHPyr content of coke oven workers was negatively correlated with TH1/TH2 ratio and IFN-γ expression level, and positively correlated with IL-4 and IL-10 levels. The IL-10 CpG-11, CpG-15 methylation rate decreased with increasing urine 1-OHPyr concentration. The side and top of the furnace worker exposed to COEs were the key targets for occupational health. The exposure of coke oven workers to COEs affected the expression of immunoregulatory cytokines. The exposure of COEs caused the change of IL-10 methylation rate.

Reduction of mitochondrial DNA copy number in peripheral blood is related to polycyclic aromatic hydrocarbons exposure in coke oven workers: Bayesian kernel machine regression

Although association between polycyclic aromatic hydrocarbons (PAHs) exposure and mitochondrial DNA copy number (mtDNAcn) was researched by traditional linear model extensively, most of these studies analyzed independent effect of each PAHs metabolite and adjust for the confounding other metabolites concomitantly, without considering others interactions. As a complex organic pollutant, a reasonable statistical method is needed to study toxic effects of PAHs.Therefore, we aimed to conduct a novel statistical approach, Bayesian Kernel Machine Regression (BKMR), to explore the effect of PAHs exposure on mtDNAcn among coke oven workers. In this cross-sectional study, the concentrations urinary of PAHs metabolites were measured using high performance liquid chromatography mass spectrometry (HPLC-MS). The mtDNAcn was measured using real-time quantitative polymerase chain reaction (RT-PCR) in peripheral blood of 696 Chinese coke oven workers. The relationship of urinary of PAHs metabolites and mtDNAcn were evaluated by BKMR model. And the results showed a significant negative effect of PAHs metabolites on mtDNAcn when PAHs metabolites concentrations were all above 35th percentile compared to the median and the statistically significant negative single-exposure effect of 2-OHNAP and 2-OHPHE on mtDNAcn when all of the other PAHs are fixed at a particular threshold (25th, 50th, 75th percentile). The changes in log 2-OHNAP and 2-OHPHE from the 25th to the 75th percentile when other PAHs metabolites were at the 50th percentile were associated with change in mtDNAcn of −0.082 (−0.021, −0.124) and −0.048 (−0.021, −0.090) respectively. And evidence of a linear effect of urinary 2-OHNAP and 2-OHPHE were found. Finally, our findings suggested that PAHs cumulative exposures and particularly single-exposure of 2-OHNAP and 2-OHPHE might compromise mitochondrial function by decreasing mtDNAcn in Chinese coke oven workers.

Dose-related telomere damage associated with the genetic polymorphisms of cGAS/STING signaling pathway in the workers exposed by PAHs

Telomeres are located at the end of eukaryotic chromosomes and vulnerable to exogenous chemical compounds. Exposure to coke oven emissions (COEs) leads to a dose-related telomere damage, and such chromosomal damage might trigger the cGAS/STING signaling pathway which plays an important role in immune surveillance. However, the relationship between the genetic variations in the cGAS/STING signaling pathway and telomere damage in the COEs-exposure workers has not been investigated. Therefore, we recruited 544 coke oven workers and 238 healthy control participants, and determined the level of COEs exposure, concentration of urinary 1-hydroxypyrene (1-OHPYR), genetic polymorphisms and telomere length. The results showed that the telomere length significantly decreased from the control-to high-exposure groups as defined by the external exposure level (P < 0.05). The results also indicated that STING rs7447927 CC, cGAS rs34413328 AA, and cGAS rs610913 AA could inhibit telomere shortening in the exposure group (P < 0.05), and cGAS rs34413328, urine 1-OHPYR and cumulative exposure dose (CED) had a significant association with telomere length by generalized linear model. In conclusion, telomere shortening was a combined consequence of short-term exposure, long-term exposure, and genetic variations among the COEs-exposure workers.

The interaction effects of smoking and polycyclic aromatic hydrocarbons exposure on the prevalence of metabolic syndrome in coke oven workers

IntroductionMetabolic syndrome (MetS) is a cluster of interrelated risk factors, which increase the risk of cardiovascular disease (CVD) and cancer. The prevalence of MetS might be affected by environmental pollution and individual’s poor lifestyles. MethodsIn this cross-sectional study, we aimed to evaluate the interactions effect of PAHs exposure and poor lifestyles on MetS among coke oven workers. We measured the concentrations of 11 urinary PAH metabolites among 682 coke oven workers by HPLC-MS. China adult blood lipid abnormality prevention guide (2016) was employed for diagnosing MetS. An interaction effect was tested in the modified Poisson regression models. ResultsThe results showed that the urinary level of 1-NAP (P for trend = 0.043) and 2-FLU (P for trend = 0.037) had significant dose-response relationships with increased PR of MetS. For 1-NAP, statistically significant positive association was with low HDL among individuals (P for trend = 0.003). Besides, smoking was associated with a significantly increased risk of prevalence ratio of MetS (PR = 1.07; 95% CI 1.00–1.13), high triglycerides (PR = 1.13; 95% CI 1.05–1.20) and low HDL (PR = 1.07; 95% CI 1.01–1.14). Smokers who with high levels of 1-NAP and 2-FLU had higher prevalence ratio of MetS compared with non-smokers who with low levels of 1-NAP [PR (95% CI): 1.17 (1.06–1.29); P for trend = 0.002] and 2-FLU [PR (95% CI): 1.17 (1.06–1.29); P for trend = 0.004]. ConclusionsOur findings suggested PAHs exposure increased the prevalence ratio of MetS and this effect can be modified by smoking status.

Polycyclic aromatic hydrocarbon exposure, miRNA genetic variations, and associated leukocyte mitochondrial DNA copy number: A cross-sectional study in China.

Mitochondria DNA was preferentially attacked by the exogenous carcinogens including polycyclic aromatic hydrocarbons (PAHs) relative to nuclear DNA, and nuclear gene variants may account for variability in the mitochondrial DNA copy number (mtDNAcn). However, it remains unclear whether miRNA genetic variations are associated with mitochondrial DNA damage in the PAH-exposed workers. Therefore, we measured the leukocyte mtDNAcn, urinary 1-hydroxypyrene (1-OHPYR), environmental PAH exposure, and miRNA genetic polymorphisms among 544 coke oven workers and 238 healthy control participants. We found that the mtDNAcn in the exposure group (0.60±0.29) was significantly lower than that in the control group (1.03±0.31) (t=18.931, P<0.001). Spearman correlation analysis showed that the peripheral blood leukocyte mtDNAcn had significantly negative correlations with the levels of 1-OHPYR and environmental PAH exposure (P<0.001). Covariance analysis indicated that miR-210 rs11246190 AA, miR-210 rs7395206 CC, and miR-126 rs2297538 GG probably promoted a decrease in leukocyte mtDNAcn in the exposure or control groups (P<0.05). In generalized linear model, miR-210 rs11246190 GG was a protective factor of mtDNAcn, and environmental PAH exposure was the risk factor of the mtDNAcn. In conclusion, the decrease of leukocyte mtDNAcn is the result of a combination of environmental and genetic factors.

Polycyclic aromatic hydrocarbons exposure and their joint effects with age, smoking, and TCL1A variants on mosaic loss of chromosome Y among coke-oven workers

Mosaic loss of chromosome Y (mLOY) is the most common structure somatic event that related to increased risks of various diseases and mortality. Environmental pollution and genetic susceptibility were important contributors to mLOY. We aimed to explore the associations of polycyclic aromatic hydrocarbons (PAHs) exposure, as well as their joint effects with age, smoking, and genetic variants on peripheral blood mLOY. A total of 1005 male coke-oven workers were included in this study and their internal PAHs exposure levels of 10 urinary PAH metabolites and plasma benzo[a]pyrene-r-7,t-8,t-9,c-10-tetrahydotetrol-albumin (BPDE-Alb) adducts were measured. mLOY was defined by the median log R ratio(mLRR) of 1480 probes in male-specific region of chromosome-Y from genotyping array. We found that the PAHs exposure levels were linearly associated with mLOY. A 10-fold increase in urinary 1-hydroxynaphthalene (1-OHNa), 1-hydroxyphenanthrene (1-OHPh), 2-OHPh, 1-hydroxypyrene (1-OHP), ΣOH-PAHs, and plasma BPDE-Alb adducts could generate 0.0111, 0.0085, 0.0069, 0.0103, 0.0134, and 0.0152 decrease in mLRR-Y, respectively. Additionally, mLOY accelerated with age, smoking pack-years, and TCL1A rs1122138-C allele, and we observed the most severe mLOY among subjects carrying more than 3 of the above risk factors. Our results revealed the linear dose-effect associations between PAHs exposure and mLOY. Elder male smokers carrying rs1122138CC genotype were the most susceptible subpopulations to mLOY, who should be given protections for PAHs exposure induced chromosome-Y aberration.

Effects of polycyclic aromatic hydrocarbon exposure and miRNA variations on peripheral blood leukocyte DNA telomere length: A cross-sectional study in Henan Province, China

Telomeres play a major role in human aging and disease, especially in most cancers. Telomere length was shortened in workers exposed to polycyclic aromatic hydrocarbons (PAHs) and influenced by individual genetic variations in telomere-binding proteins. MicroRNAs (miRNAs) can affect the progress of messenger RNA (mRNA) transcription; however, whether polymorphisms in miRNA can act on the telomere length is still unknown. Therefore, we aimed to explore the relationships between telomere damage and genetic polymorphisms in miRNA or environmental exposure. A total of 544 coke oven workers and 238 healthy controls were recruited. After collecting peripheral blood and extracting the genomic DNA of the study subjects, the telomere length (TL) in their leucocytes was detected by a real-time quantitative polymerase chain reaction (PCR), and polymorphisms in miRNAs were genotyped using the flight mass spectrometry technique. The concentrations of the four urine OH-PAHs were determined by high performance liquid chromatography (HPLC), and the Soxhlet extraction method was used to detect the concentration of coke oven emissions (COEs) in the air. We found that the peripheral blood leucocyte DNA TL was significantly shorter in the exposure group (0.75; 0.51, 1.08) than that in the control group (1.05; 0.76, 1.44) (Z = 7.692, P < 0.001). The total cumulative exposure dose (CED), 1-hydroxypyrene, 2-hydroxynaphthalene, and 3-hydroxyphenanthrene were significantly negatively correlated with TL (r = −0.307, P < 0.001; r = −0.212, P < 0.001; r = −0.110, P = 0.025; r = −0.251, P < 0.001, respectively). MiR-145 rs353291 GG, miR-30a rs2222722 CT/CC, and miR-197 rs1889470 AA could protect the telomere end in the exposed workers (P < 0.05). The interaction between miR-197 rs1889470 and the CED had an effect on TL (β = 0.066, P = 0.034). This is the first study to evaluate gene–environmental interactions for miRNA polymorphisms and PAH exposure in coke oven workers.

Heat-shock protein 70 (HSP70) polymorphisms affect the risk of coke-oven emission-induced neurobehavioral damage

ObjectivesEpidemiology studies indicated that coke-oven workers with long-term exposure to polycyclic aromatic hydrocarbons (PAHs) often have some neurobehavioral abnormalities especially impairment for cognitive function, while the underlying mechanisms are not fully understood. Numerous studies have indicated the antioxidant and anti-apoptosis roles of heat shock protein 70 (Hsp70). The genetic polymorphisms in HSP70 genes are associated with multiple diseases including neurotoxicity. However, it is unclear whether HSP70 polymorphisms are related to the neurotoxicity of PAH. We, therefore, investigate the possible association between HSP70 polymorphisms and neurobehavioral abnormalities. Methods188 coke-oven workers and 137 control workers were recruited in this study. Emotional and cognitive function was assessed using the WHO/NCTB. HSP70 polymorphisms (HSP70-1 G190C, HSP70-2 G1267 A and HSP70-hom T2437C) were checked by PCR-RFLP. ResultsThe results indicated that HSP70-1 CC genotypes in coke-oven workers were associated with poor neurobehavioral performance such as the attention /response speed and visual perception/memory, while the HSP70-2 AA genotypes were associated with lower short-term auditory memory. ConclusionsHSP70-1 CC and HSP70-2 AA genotypes in coke-oven workers may increase the risk for neurobehavioral damage, especially attention, learning and memory.

Polycyclic aromatic hydrocarbons associated long non-coding RNAs and heart rate variability in coke oven workers

TPS 791: Occupational health 1, Exhibition Hall, Ground floor, August 26, 2019, 3:00 PM - 4:30 PM Aim: To evaluate the association between polycyclic aromatic hydrocarbon (PAH) related long non-coding RNAs (lncRNAs) and heart rate variability (HRV) indices in coke oven workers. Methods: A two-stage study was performed to identify lncRNAs associated with PAH exposures quantified using urinary monohydroxy-PAH metabolites and plasma benzo[a]pyrene-r-7, t-8,c-10-tetrahydrotetrol-albumin adducts. In discovery stage, we used Human 8X60k LncRNA Arrays to test different expression in plasma lncRNA between 12 exposed workers and 12 controls matching age, sex, and smoking. We validated associations with four selected lncRNAs in 403 coke oven workers by droplet digital polymerase chain reaction (the QX-200 system, Bio-Rad, Hercules, CA). Results: In the discovery stage, lncRNA expression profiles differed between the exposed and control groups, with 58 lncRNAs significantly down-regulated and 5 lncRNAs mildly up-regulated in the exposed group (fold change’s cutoff is 10 and false discovery rate <0.05). In the validation analysis, two lncRNAs were consistent with the chip results. In male, evaluated urinary1-hydroxynaphthalene and 2-hydroxyphenanthrene were significantly associated with lower ENST00000447277 expression (β=−0.200 and β=−0.286); while evaluated 2-hydroxyfluorene, total concentration of hydroxyfluorene, 2-hydroxyphenanthrene, total concentration of hydroxyphenanthrene and total concentration of all PAH metabolites were associated with lower NR_024564 expression (all P.< 0.05). These lncRNAs were associated with lower HRV. Moreover, the 2 lncRNAs were positively associated with the root mean of square of successive differences between adjacent normal NN intervals (β= 0.032 and β=0.036), and NR_024564 was positively related to high-frequency power (0.15 to 0.40 Hz) (β=0.077, all P< 0.05). However, in female, we only found increased urinary 4-hydroxyphenanthrene was related to lower ENST00000447277 expression (β=−0.145, P=0.034), and no significant association between ENST00000447277 and HRV. Conclusions: Associations of PAH exposures with lncRNA expression, and of lncRNA expression with HRV, suggested that lncRNAs might be a novel mechanism mediating the effects of PAH exposure on early cardiovascular damage.

Heart rate variability mediate the association between polycyclic aromatic hydrocarbons exposure and atherosclerotic cardiovascular disease risk in coke oven workers

Heart rate variability mediate the association between polycyclic aromatic hydrocarbons exposure and atherosclerotic cardiovascular disease risk in coke oven workers