miR-145a-5p/SIK1/cAMP-dependent alteration of synaptic structural plasticity drives cognitive impairment induced by coke oven emissions.

Exposure to fine particulate matter (PM) is associated with the neurodegenerative diseases. Coke oven emissions (COEs) in occupational environment are important sources of PM. However, its neurotoxicity is still unclear. Therefore, evaluating the toxicological effects of COE on the nervous system is necessary. In the present study, we constructed mouse models of COE exposure by tracheal instillation. Mice exposed to COE showed signs of cognitive impairment. This was accompanied by a decrease in miR-145a-5p and an increase in SIK1 expression in the hippocampus, along with synaptic structural damage. Our results demonstrated that COE-induced miR-145a-5p downregulation could increase the expression of SIK1 and phosphorylated SIK1, inhibiting the cAMP/PKA/CREB pathway by activating PDE4D, which was associated with reduced synaptic structural plasticity. Furthermore, restoring of miR-145a-5p expression based on COE exposure in HT22 cells could partially reversed the negative effects of COE exposure through the SIK1/PDE4D/cAMP axis. Collectively, our findings link epigenetic regulation with COE-induced neurotoxicity and imply that miR-145a-5p could be an early diagnostic marker for neurological diseases in patients with COE occupational exposure.

Effect and interaction of TNKS genetic polymorphisms and environmental factors on telomere damage in COEs-exposure workers.

Coke oven emissions (COEs) contain many carcinogenic polycyclic aromatic hydrocarbons (PAHs). Telomere damage is an early biological marker reflecting long-term COEs-exposure. Whereas, whether the genetic variations of telomere-regulated gene TNKS have an effect on the COEs-induced telomere damage is unknown. So we detected the environmental exposure levels, relative telomere length (RTL), and TNKS genetic polymorphisms among 544 COEs-exposure workers and 238 healthy participants. We found that the RTL of the wild homozygous GG genotype in rs1055328 locus was statistically shorter compared with the CG+CC genotype for the healthy participants using covariance analysis(P = 0.008). In the Generalized linear model (GLM) analysis, TNKS rs1055328 GG could accelerate telomere shortening (P = 0.011); and the interaction between TNKS rs1055328 GG and COEs-exposure had an effect on RTL (P = 0.002). In conclusion, this study was the first to discover the role of TNKS rs1055328 locus in COEs-induced telomere damage, and proved that chromosomal damage was a combined consequence of environmental and genetic factors.

The polymorphisms in cGAS-STING pathway are associated with mitochondrial DNA copy number in coke oven workers.

OBJECTIVE: To evaluate the interaction effects of Polycyclic aromatic hydrocarbons (PAHs) exposure and variants in cGAS-STING genes on mitochondrial DNA copy number (mtDNAcn) in workers. METHODS: The mtDNAcn was determined by real-time quantitative polymerase-chain reaction in 544 PAHs-exposed workers and 238 office workers. The polymorphisms were detected by flight mass spectrometry. RESULTS: The mtDNAcn in PAHs exposure group was significantly lower than non-occupational exposure population (P < 0.00). The cGAS rs610913 CA+AA had significant interaction effects with STING rs11554776 GG+GA (P = 0.035), rs7380824 CC+CT (P = 0.026), and rs78233829 GC+CC (P = 0.034) on mtDNAcn. The generalized linear model results showed that the influencing factors of mtDNAcn include PAHs exposure (P < 0.001) and the interaction of PAHs exposure and cGAS rs 311678 AA+AG (P = 0.047). CONCLUSION: The influencing factors of mtDNAcn include PAHs exposure and the interaction of PAHs exposure and cGAS rs 311678 AA+AG.

[Study on the relationship between the pathological type of lung cancer caused by coke oven discharge and the contact type and exposure time].

Objective: To study the pathological types of lung cancer caused by coke oven emissions and analyze the correlation between different exposure levels. Methods: In October 2020, the relevant data of 86 confirmed cases of lung cancer caused by coke oven emissions (including basic information of patients, relevant occupational exposure and clinical data) were collected, The workers were grouped according to the different COEs concentrations in their posts: workers in auxiliary posts were taken as the low exposure group (11 persons) , The workers at coke side and furnace bottom are the medium exposure group (14 persons) , and the workers at furnace top are the high exposure group (61 persons) , and the correlation between pathological types of lung cancer and different exposure levels was analyzed. Results: There was no significant difference in age and length of service among the groups (P>0.05) ; The number of lung cancer cases and pathological types among workers in each group were statistically significant (P=0.044) . After adjusting for interference factors, the number of undifferentiated cancers (mainly small cell lung cancer) increased with the increase of exposure level, with a statistically significant difference (P=0.001) . The incidence of lung cancer increased gradually with the length of service, and the incidence rate of lung cancer among workers of different working ages was statistically significant (P<0.05) . Conclusion: Undifferentiated small cell carcinoma is the most common pathological type of lung cancer caused by coke oven emissions, and the incidence of lung cancer tends to increase with the length of service.

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.

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

OBJECTIVE: 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. METHODS: 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. RESULTS: The urine 1-hyroxy-pyrene(1-OHPyr) content of coke oven workers was higher than that of the control group(F=12. 446, P<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<0. 05), and serum IFN-γ content of coke oven workers decreased(F=46. 379, P<0. 05), the serum IL-4 content of coke oven workers increased(F=17. 426, P<0. 05), the serum IL-10 content of coke oven workers increased(F=33. 515, P<0. 05), and the TH1/TH2 ratio of coke oven workers decreased(F=21. 677, P<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. CONCLUSION: 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.

Benchmark dose assessment for coke oven emissions-induced telomere length effects in occupationally exposed workers in China.

Telomeres are DNA-protein structures that protect chromosome ends from degradation and fusion, which are shortened by oxidative stress, for example air pollution including benzene, toluene, Coke Oven Emissions (COEs), and so on. As a biomarker of health and disease, telomere length is associated with cardiovascular, diabetes and cancers. The aim of this study was to estimate the effects of COEs exposure on telomere length and the benchmark dose (BMD) of COEs. A total of 542 coke oven workers and 235 healthy controls without exposure to toxicants were recruited. Quantitative PCR was used to determine the telomere length in human peripheral blood leukocytes DNA. Propensity scoring was used to match coke oven workers to healthy controls. Linear regression models and trend tests were used to the relationship between COEs exposure and telomere length. Telomere length in COEs exposed group 0.764 (0.536, 1.092) was significantly shorter than that in the control group 1.064(0.762, 1.438), (P < 0.001). There were significantly dose-response relationships between COEs exposure and telomere damage with telomere length as a biomarker. A BMDL value lower than the present occupational exposure limits (OELs) of COEs exposure was evaluated using the BMD approach in coke oven workers. Our results suggested that shorter telomere length is related to occupational exposure to COEs and the level of COEs exposure lower than the current national OELs in China and many other countries could induce telomere damage.

Benchmark Dose Assessment for Coke Oven Emissions-Induced Mitochondrial DNA Copy Number Damage Effects.

Objective: The study aimed to estimate the benchmark dose (BMD) of coke oven emissions (COEs) exposure based on mitochondrial damage with the mitochondrial DNA copy number (mtDNAcn) as a biomarker. Methods: A total of 782 subjects were recruited, including 238 controls and 544 exposed workers. The mtDNAcn of peripheral leukocytes was detected through the real-time fluorescence-based quantitative polymerase chain reaction. Three BMD approaches were used to calculate the BMD of COEs exposure based on the mitochondrial damage and its 95% confidence lower limit (BMDL). Results: The mtDNAcn of the exposure group was lower than that of the control group (0.60 ± 0.29 vs. 1.03 ± 0.31; P < 0.001). A dose-response relationship was shown between the mtDNAcn damage and COEs. Using the Benchmark Dose Software, the occupational exposure limits (OELs) for COEs exposure in males was 0.00190 mg/m 3. The OELs for COEs exposure using the BBMD were 0.00170 mg/m 3 for the total population, 0.00158 mg/m 3 for males, and 0.00174 mg/m 3 for females. In possible risk obtained from animal studies (PROAST), the OELs of the total population, males, and females were 0.00184, 0.00178, and 0.00192 mg/m 3, respectively. Conclusion: Based on our conservative estimate, the BMDL of mitochondrial damage caused by COEs is 0.002 mg/m 3. This value will provide a benchmark for determining possible OELs.

Chain-mediating effect of interaction between telomeres and mitochondria under oxidative stress in coke oven workers.

Coke oven emissions (COEs) exposure leads to oxidative stress, an imbalance between oxidant production and antioxidant defence in the body, which then leads to shortened relative telomere length (RTL) and reduced mitochondrial DNA copy number (mtDNAcn), ultimately leading to ageing and disease. By analysing the relationship among COEs, oxidative stress, RTL and mtDNAcn, we investigated the chain-mediating effects of oxidative stress and telomeres on mitochondrial damage and mitochondria on telomere damage in coke oven workers. A total of 779 subjects were included in the study. Cumulative COEs exposure concentrations were estimated, and the RTL and mtDNAcn of peripheral blood leukocytes were measured using real-time fluorescence quantitative PCR. Total antioxidant capacity (T-AOC) was measured to reflect the level of oxidative stress. The data were statistically analysed using SPSS 21.0 software and discussed using mediation effect analysis. After adjusting for age, sex, smoking, drinking and BMI, generalised linear model revealed dose-response associations between COEs and T-AOC, RTL and mtDNAcn, respectively. (Ptrend < 0.05). The results of chain-mediating effect showed that the proportion of the chain-mediating effect of "CED-COEs→T-AOC→ RTL→mtDNAcn" was 0.82% (ß = -0.0005, 95% CI = [-0.0012, -0.0001]), and the proportion of the chain-mediating effect of "CED-COEs→T-AOC→ mtDNAcn → RTL ″ was 2.64% (ß = -0.0013, 95% CI = [-0.0025, -0.0004]). After oxidative stress is induced by COEs, mitochondria and telomeres may interact with each other while leading further to potential bodily damage. This study provides clues to explore the association between mitochondria and telomeres.

Trend Analysis of Occupational Lung Cancer from Coke Oven Emission Exposure - China, 2008-2019.

What is already known about this topic?: Coke oven emissions are a complex mixture of particulate matter and gases, some with carcinogenicity, released during coke production. Lung cancer caused by coke oven emissions has been listed as a statutory occupational cancer in China and many countries. What is added by this report?: In this study, coke oven emissions-induced lung cancer was mainly found in the manufacturing industries. Coke oven workers exposed to higher levels of polycyclic aromatic hydrocarbons in different workplaces had a high risk of occupational lung cancer. What are the implications for public health practice?: It is necessary to take efforts to greatly reduce emissions from coke production and effectively monitor the health of workers.

Relationship between miRNAs polymorphisms and peripheral blood leukocyte DNA telomere length in coke oven workers: A cross-sectional study.

OBJECTIVE: The purpose of this study was to investigate the factors affecting telomere length (TL) in coke oven workers by analyzing the interaction between miRNAs polymorphisms and coke oven emissions (COEs) exposure. METHODS: A total of 544 coke oven workers and 238 healthy controls were recruited. Peripheral blood was collected from the subjects, genomic DNA was extracted, leukocyte TL was detected by real-time quantitative polymerase chain reaction, and fifteen polymorphisms of eight miRNAs were genotyped by flight mass spectrometry. RESULTS: Statistical analysis showed that the peripheral blood DNA TL in the exposure group was shorter than that in the control group (P < 0.001). Generalized linear model found that COEs-exposure [ß (95%CI) = -0.427 (-0.556, -0.299), P < 0.001], genotype CC+CT for miR-612 rs1144925 [ß (95%CI) = -0.367 (-0.630, -0.104), P = 0.006], and the interaction of miR-181B1 rs12039395 TT genotype and COEs-exposure [ß (95% CI) = 0.564 (0.108, 1.020), P = 0.015] were associated with the shortened TL. CONCLUSION: COEs-exposure and miR-612 rs1144925 TT could promote telomere shortening in coke oven workers. The interaction of miR-181B1 rs12039395 TT genotype and COEs-exposure could protect telomere. This provides clues for further mechanistic studies between miRNA and telomere damage.

The Association Between Polymorphisms in Cell-Cycle Genes and Mitochondrial DNA Copy Number in Coke Oven Workers.

The mitochondrial DNA (mtDNA) copy number is a vital component in maintaining normal mitochondrial function. It is affected by environmental and occupational exposures, as well as polymorphisms in nuclear genes. Nonetheless, the specific roles of polymorphisms in cell-cycle genes and mtDNA copy number are still unknown. This study enrolled a sample of 544 coke oven workers and 238 non-exposed controls so as to assess the effect of exposure of coke oven emissions (COEs) and polymorphisms in cell-cycle genes on the mtDNA copy number. We found that the mtDNA copy number in the exposed group (0.60 ± 0.29) was significantly lower than that in the control group (1.03 ± 0.31) (t =18.931, P < 0.001). The analysis of covariance showed that both the rs1801270 (CA+CC) and the rs1059234 (CT+CC) in p21 gene were associated with lower mtDNA copy number in the exposed group (P = 0.001). Generalized linear models indicated COEs-exposure (ß = -0.432, P < 0.001) and rs1059234 (CT+CC) in p21 gene (ß = -0.060, P = 0.024) were the factors in mtDNA copy number reduction. In conclusion, this study suggests that the decrease of the mtDNA copy number is associated with COEs-exposure and the rs1059234 (CT+CC) in the p21 gene.

Estimations of benchmark dose for urinary metabolites of coke oven emissions among workers.

Coke oven emissions (COEs), usually composed of polycyclic aromatic hydrocarbons (PAHs) and so on, may alter the relative telomere length of exposed workers and have been linked with adverse health events. However, the relevant biological exposure limits of COEs exposure has not been evaluated from telomere damage. The purpose of this study is to estimate benchmark dose (BMD) of urinary PAHs metabolites from COEs exposure based on telomere damage with RTL as a biomarker. A total of 544 exposed workers and 238 controls were recruited for participation. High-performance liquid chromatography and qPCR were used to detect concentrations of urinary mono-hydroxylated PAHs and relative telomere length in peripheral blood leukocytes for all subjects. The benchmark dose approach was used to estimate benchmark dose (BMD) and its lower 95% confidence limit (BMDL) of urinary OH-PAHs of COEs exposure based on telomere damage. Our results showed that telomere length in the exposure group (0.75 (0.51, 1.08)) was shorter than that in the control group (1.05 (0.76,1.44))(P < 0.05), and a dose-response relationship was shown between telomere damage and both 1-hydroxypyrene and 3-hydroxyphenanthrene in urine. The BMDL of urinary 1-hydroxypyrene from the optimal model for telomere damage was 1.96, 0.40, and 1.01 (µmol/mol creatinine) for the total, males, and females group, respectively. For 3-hydroxyphenanthrene, the BMDL was 0.94, 0.33, and 0.49 (µmol/mol creatinine) for the total, males, and females. These results contribute to our understanding of telomere damage induced by COEs exposure and provide a reference for setting potential biological exposure limits.

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.

Genetic polymorphisms, mRNA expression levels of telomere-binding proteins, and associates with telomere damage in PAHs-Exposure workers.

Coke oven emissions (COEs), confirmed human carcinogens, are mainly composed of polycyclic aromatic hydrocarbons (PAHs). Telomere shortening in blood leukocytes has been associated with COEs, and polymorphisms in metabolic enzymes. However, the relationship between polymorphisms in telomere related genes and telomere shortening in COEs exposed workers has never been evaluated. Therefore, we measured telomere length and mRNA expression levels of telomere-binding proteins (TBPs) by qPCR method in leucocyte from 544 COEs exposed workers and 238 office staffs (referents). Flight mass spectrometry was used to perform the genotyping of selected functional and susceptible SNPs. The results showed that the telomere length in the exposure group 0.75(0.51,1.08) was significantly shorter than that in the control group 1.05(0.76,1.44) (P < 0.001). The mRNA expression levels of TPP1, TERF1 and TERF2 genes in the exposure group were significantly lower than those in the control group (P < 0.05), the mRNA expression level of POT1 in the exposure group was significantly higher than that in the control group (P < 0.05). We used the wild homozygous genotype as a reference, subjects carrying TERT rs2736109 AA, TERT rs3215401 CC and TERT rs2736100 GT + GG genotypes had significantly longer telomere length in the exposure group (P < 0.05). In conclusion, the workers exposed to COEs had shorter telomere length, which was regulated by the TPP1, TERF1, TERF2 and POT1 genes expression levels, and the gene polymorphisms of TERT gene were associated with the telomere length among PAHs-exposure workers.

FLT1 hypermethylation is involved in polycyclic aromatic hydrocarbons-induced cell transformation.

Coke oven emissions (COEs) are common particle pollutants in occupational environment and the major constituents of COEs are polycyclic aromatic hydrocarbons (PAHs). Previously, we identified aberrant methylation of the fms related tyrosine kinase 1 (FLT1) gene over the course of benzo(a)pyrene (BaP)-induced cell transformation via genome-wide methylation array. To quantify FLT1 methylation, we established a bisulfite pyrosequencing assay and examined the FLT1 hypermethylation in several human cancers. The results revealed that 70.0% (21/30 pairs) of lung cancers harbored hypermethylated FLT1 and concomitant suppression of gene expression compared to the adjacent tissues. This implies that FLT1 hypermethylation might play a role in malignant cell transformation. In addition, FLT1 hypermethylation and gene suppression appeared in primary human lymphocytes in a dose-response manner following COEs treatment. To explore whether FLT1 methylation is correlated with COEs exposure and DNA damage, we recruited 144 male subjects who had been exposed to high levels of COEs and 84 male control subjects. Notably, the FLT1 methylation in peripheral blood lymphocytes (PBLCs) of the COEs-exposed group (19.8 ±â€¯3.2%) was enhanced by 17.9% compared to that of the control group (16.8 ±â€¯2.8%) (P < 0.001). The FLT1 methylation status was positively correlated with urinary 1-hydroxypyrene (1-OHP) levels, an internal exposure marker of PAHs (ß = 0.029, 95% CI = 0.010-0.048, P = 0.003) and positively correlated with DNA damage (ßOTM = 0.024, 95% CI = 0.007-0.040, P = 0.005; ßTail DNA = 0.035, 95% CI = 0.0017-0.054, P < 0.001) indicated by comet assay. Taken together, these findings indicate that FLT1 might be a tumor suppressor, and its hypermethylation might contribute to PAHs-induced carcinogenicity.

Benchmark Dose Assessment for Coke Oven Emissions-Induced Mitochondrial DNA Copy Number Damage Effects / 生物医学与环境科学（英文）

OBJECTIVE@#The study aimed to estimate the benchmark dose (BMD) of coke oven emissions (COEs) exposure based on mitochondrial damage with the mitochondrial DNA copy number (mtDNAcn) as a biomarker.@*METHODS@#A total of 782 subjects were recruited, including 238 controls and 544 exposed workers. The mtDNAcn of peripheral leukocytes was detected through the real-time fluorescence-based quantitative polymerase chain reaction. Three BMD approaches were used to calculate the BMD of COEs exposure based on the mitochondrial damage and its 95% confidence lower limit (BMDL).@*RESULTS@#The mtDNAcn of the exposure group was lower than that of the control group (0.60 ± 0.29 vs. 1.03 ± 0.31; P < 0.001). A dose-response relationship was shown between the mtDNAcn damage and COEs. Using the Benchmark Dose Software, the occupational exposure limits (OELs) for COEs exposure in males was 0.00190 mg/m 3. The OELs for COEs exposure using the BBMD were 0.00170 mg/m 3 for the total population, 0.00158 mg/m 3 for males, and 0.00174 mg/m 3 for females. In possible risk obtained from animal studies (PROAST), the OELs of the total population, males, and females were 0.00184, 0.00178, and 0.00192 mg/m 3, respectively.@*CONCLUSION@#Based on our conservative estimate, the BMDL of mitochondrial damage caused by COEs is 0.002 mg/m 3. This value will provide a benchmark for determining possible OELs.

Organic extracts of coke oven emissions can induce genetic damage in metabolically competent HepG2 cells.

Coke oven emissions (COEs) containing various carcinogenic polycyclic aromatic hydrocarbons (PAHs) represent the coal-burning pollution in the air. Organic pollutants in the aerosol and particulate matter of COEs were collected from the bottom, side, and top of a coke oven. The Comet assay and cytokinesis-block micronucleus cytome assay were conducted to analyze the genetic damage of extractable organic matter (EOM) of COEs on HepG2 cells. All the three EOMs could induce significant dose-dependent increases in Olive tail moment, tail DNA, and tail length, micronuclei, nucleoplasmic bridges, and nuclear buds frequencies, which were mostly positively correlated with the total PAHs concentration in each EOM. In conclusion, EOMs of COEs in the three typical working places of coke oven can induce DNA strand breaks and genomic instability in the metabolically competent HepG2 cells. The PAHs in EOMs may be important causative agents for the genotoxic effects of COEs.

Mechanism of coke oven emissions-induced acute toxicity in HL-60 cells / 中国职业医学

OBJECTIVE: To establish the cell model using human leukemia cell line HL-60 for exposure of coke oven emissions( COE) in vitro and to explore the mechanism of COE-induced acute toxicity in HL-60 cells. METHODS: HL-60 cells were collected in their logarithmic growth phase and cultured in medium that had final concentrations of COE in 2. 5,5. 0,10. 0 and 20. 0 mg / L for 24 hours. Cell survival rate was examined by CCK-8 assay. The cytotoxicity was evaluated using lactate dehydrogenase release assay. Reactive oxygen species( ROS) production was determined by the 2',7'-dichlorofluorescein diacetate and nitroblue tetrazolium method. The activation of nuclear factor-κB( NF-κB) pathway was evaluated by western blot. RESULTS: With the increasing exposure concentrations of COE,the cytotoxicity of HL-60 cells increased( P < 0. 01),the cell survival rate decreased( P < 0. 01),intracellular ROS decreased( P < 0. 01),whereas extracellular ROS increased( P < 0. 01). These changes had a dose-effect relationship. The levels of phospho-nuclear factor-kappa B p65 and phospho-inhibitor of kappa Bα were higher in all the COE-treated cells compared with untreated cells( P < 0. 05),with no dose-effect relationship. CONCLUSION: COE could cause acute toxicity in HL-60 cells in a doseeffect relationship. The mechanism may be related to the COE-induced in-balanced ROS release and removal,leading to the activation of NF-κB pathway. HL-60 cells can be used as a common cell line for COE hematotoxicity analysis.

Influencing factors of urinary hydroxyl metabolites of polycyclic aromatic hydrocarbons in coke oven workers / 中国职业医学

OBJECTIVE: To observe the levels of four hydroxylated metabolites of polycyclic aromatic hydrocarbons(PAHs)in the urine of coke workers and its influencing factors.To explore the feasibility of using PAHs as biomarkers for exposure of coke oven emissions(COEs).METHODS: A cross-sectional survey was used to compare 261 coke oven workers in a coke oven plant as exposure group with 111 workers without COEs exposure in an oxygen making plant as control group.Ultra high liquid chromatography-mass spectrometry was used to detect four hydroxylated metabolites of PAHs,including1-hydroxypyrene(OHP),1-hydroxynaphthalene(OHN),2-OHN and 3-hydroxyphenanthrene,in urine of these two groups.RESULTS: The levels of four hydroxylated metabolites of PAHs in urine in exposure group were higher than that of the control group(P<0.01).The levels of urinary 1-OHP,1-OHN,2-OHN were followed by the sequence of bottomoven,side-oven,and top-oven subgroups among the exposure group(P<0.05).The multiple linear regression results indicated that the levels of urinary 1-OHP,1-OHN,2-OHN were correlated with COEs exposure(P<0.05),after adjusting the confounding factors of gender,age,length of service,smoking status and alcohol drinking status.The levels of urinary 1-OHP,1-OHN,2-OHN of the exposure group increased with the increase of COEs exposure levels showing a dose-effect relationship(P<0.01).The levels of 1-OHN and 2-OHN were associated with smoking apart from COEs exposure(P<0.01).CONCLUSION: The urinary 1-OHP can be used as a reliable biomarker for the evaluation of internal exposure to COEs.The 1-OHN and 2-OHN can be used as adjuvant biomarkers.