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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.

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. 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. 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). The influencing factors of mtDNAcn include PAHs exposure and the interaction of PAHs exposure and cGAS rs 311678 AA+AG. [ABSTRACT FROM AUTHOR]

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. 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). 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/m3. The OELs for COEs exposure using the BBMD were 0.00170 mg/m3 for the total population, 0.00158 mg/m3 for males, and 0.00174 mg/m3 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/m3 respectively. Based on our conservative estimate, the BMDL of mitochondrial damage caused by COEs is 0.002 mg/m3. This value will provide a benchmark for determining possible OELs. [ABSTRACT FROM AUTHOR]

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 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 (β = −0.432, P < 0.001) and rs1059234 (CT+CC) in p21 gene (β = −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.

Objective: This project aims to enhance the occupational health insurance for coke oven workers. Methods: A total of 136 coke oven emissions workers and 61 oxygen plant workers were recruited to receive physical examinations. The coke oven emissions concentration at the workplace was measured by weighing method. The CC16 concentration was detected by enzyme-linked immunosorbent assay. Results: Logistic regression analysis revealed that exposure to coke oven emissions was correlated with CC16. Correlation analysis revealed that CC16 was related to some physical examination indicators. Multivariate general linear models showed that CC16 was indeed positively correlated with albumin after adjusting for confounding factors. Conclusions: Coke oven emissions affected multiple tissues and multiple systems. The blood system might be the earliest system affected and could be detected by the CC16 protein concentration. [ABSTRACT FROM AUTHOR]

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. [Display omitted] • COE exposure can induce spatial learning and memory impairment in mice. • COE exposure can damage neurons by reducing synaptic structural plasticity. • miR-145a-5p/SIK1/cAMP axis play important role in COE reduced synaptic structural plasticity. • Overexpression miR-145a-5p in HT22 cells can partially rescued the synaptic structural plasticity damage induced by COE. • Our findings link the epigenetic regulation with COE induced neurotoxicity and imply that miR-145a-5p may serves as a diagnostic marker for COE induced cognitive impairment. [ABSTRACT FROM AUTHOR]

Objective To comprehensively analyze the correlation between coke oven emissions and death of occupational lung cancer, and provide scientific basis for effective intervention measures and prevention decisions. Methods The published articles on occupational lung cancer caused by coke oven emissions were searched from the PubMed, CNKI, VIP, Wanfang data and Web of Science databases. The effective data from these literatures was analyzed using a meta-analysis of binary variables with the relative risk of mortality (RR) as the effect size. Stata 12.0 software was used for statistic analysis. Results Nine literatures of cohort studies were involved, including four English literatures and five Chinese literatures. Using the random effect model, total relative risk effect size was 2.24(95%CI: 1.75-2.87, Z=6.42, P < 0.05), indicating that the mortality of workers in the group exposed to coke oven emissions was higher than that of the control group. In subgroup analysis, the published year, country, follow-up time and NOS score were the sources of heterogeneity. Funnel plot method, Begg method and Egger's method results showed that there was no publication bias in our research and the result was stable. Conclusion The mortality rate of occupational lung cancer caused by coke oven emissions is high, and coke oven workers should take effective measures to reduce the exposure of coke oven emissions.

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. Image 1 • Workers exposed to COEs had shorter RTL, regulated by TPP1 , TERF1 , TERF2 and POT1 genes. • TERT gene polymorphisms were associated with the RTL. [ABSTRACT FROM AUTHOR]

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. (P trend < 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% (β = −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% (β = −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. [Display omitted] • Interaction between mtDNAcn and RTL occurs after oxidative stress induced by COEs. • The first study of chain mediation between COEs, oxidative stress, RTL, and mtDNAcn. • A mediating effect model for COEs, oxidative stress, RTL, and mtDNAcn is proposed. [ABSTRACT FROM AUTHOR]

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. • Cumulative exposure dose (CED), and 1-OHPYR were significantly negatively correlated with RTL. • TNKS rs1055328 GG could promote telomere damage. • The interaction between TNKS rs1055328 GG and COEs-exposure had an effect on RTL. [ABSTRACT FROM AUTHOR]

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. 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. 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 [ β (95%CI) = - 0.427 (−0.556, −0.299), P < 0.001], genotype CC+CT for miR-612 rs1144925 [ β (95%CI) = −0.367 (−0. 630, −0.104), P = 0.006], and the interaction of miR-181B1 rs12039395 TT genotype and COEs-exposure [ β (95% CI) = 0.564 (0. 108, 1.020), P = 0.015] were associated with the shortened TL. 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. • MiR-612 rs1144925 CC+CT genotype could promote telomere shortening. • The interaction of miR-181B1 rs12039395 TT genotype and COEs-exposure could protect telomere. • The polymorphisms in miR-132, miR-34A, miR-142, miR-495, miR-181A2, and miR-134 have no correlation with telomere. [ABSTRACT FROM AUTHOR]

Highlights: [•] The EOMs induced significant dose-dependent increases in DNA and chromosome damage. [•] The EOMs induced genotoxic damage with the highest extent for the Top-EOM. [•] Positive correlations between PAHs concentration and genetic damage were observed. [•] PAHs in EOMs may be important causative agents for the genotoxic effects of COEs. [•] The comet and CBMN assay could assess the early genetic damage of COEs at low doses. [Copyright &y& Elsevier]

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.

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 (β = -0.432, P < 0.001) and rs1059234 (CT+CC) in p21 gene (β = -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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Wang, Tan, Wang, Duan, Lappe, Shi, Yang and Shi.)

Abstract: Coke oven emissions are known as human carcinogen, which is a complex mixture of polycyclic aromatic hydrocarbon. In this study, we aimed to clarify the mechanism of action of coke oven emissions induced carcinogenesis and to identify biomarkers of early biological effects in a human bronchial epithelial cell line with CYP1A1 activity (HBE-CYP1A1). Particulate matter was collected in the oven area on glass filter, extracted and analyzed by GC/MS. DNA breaks and oxidative damage were evaluated by alkaline and endonucleases (FPG, hOGG1 and ENDO III)-modified comet assays. Cytotoxicity and chromosomal damage were assessed by the cytokinesis-block micronucleus cytome (CBMN-Cyt) assay. The cells were treated with organic extract of coke oven emissions (OE-COE) representing 5, 10, 20, 40μg/mL extract for 24h. We found that there was a dose–effect relationship between the OE-COE and the direct DNA damage presented by tail length, tail intensity and Olive tail moment in the comet assay. The presence of lesion-specific endonucleases in the assays increased DNA migration after OE-COE treatment when compared to those without enzymes, which indicated that OE-COE produced oxidative damage at the level of pyrimidine and purine bases. The dose-dependent increase of micronuclei, nucleoplasmic bridges and nuclear buds in exposed cells was significant, indicating chromosomal and genomic damage induced by OE-COE. Based on the cytotoxic biomarkers in CBMN-Cyt assay, OE-COE may inhibit nuclear division, interfere with apoptosis, or induce cell necrosis. This study indicates that OE-COE exposure can induce DNA breaks/oxidative damage and genomic instability in HBE-CYP1A1 cells. The FPG-comet assay appears more specific for detecting oxidative DNA damage induced by complex mixtures of genotoxic substances. [Copyright &y& Elsevier]

A repeated measurement cohort study was conducted to determine whether 2-napthol can be a suitable biomarker for evaluating the magnitude of exposure to PAHs from coke oven emissions. Time-course patterns of urinary 2-naphthol levels in coke-oven workers were examined. Also, the correlation between urinary 2-naphthol levels and PAHs from personal breathing zone samples was analyzed while examining and adjusting possible confounding factors, such as smoking alcohol consumption, and age of human subjects. A total of 8 spot urine samples were collected from each high-exposure group (topside-oven workers, n = 17) and low-exposure group (side-oven workers, n = 25) during the whole working cycle, which consists of six consecutive working days followed by 2 days off. Personal breathing zone samples were collected to quantify PAH intake. A questionnaire was distributed and collected from each worker for assessment of demographic parameters. Our results confirmed that the topside-oven area contained significantly higher PAH levels than the side-oven area. Urinary 2-naphthol levels correlated with the levels of PAH species, including pyrene, benzo[k]fluoranthene, benezo[g,h,i]pyrene, naphthalene, phenanthrene, anthracene, indeno[1,2,3-cd]pyrene, benzo[k]fluoranthene, and total PAHs. During the working cycle, urinary 2-naphthol levels remained stable at around 46-97 ng/mg creatinine during the working days and dramatically increased during the off days. After stratification of data based on smoking status, smokers had significantly higher urinary 2-naphthol levels than non-smokers, and 2-naphthol levels positively correlated with smoking status. Coke-oven emissions are a source of exposure to naphthalene. Also, smoking is a significant source of exposure to naphthalene and served as a confounder factor. Due to its abundance, positive association with total PAHs and certain carcinogenic PAH compounds, and slower elimination kinetics, urinary 2-naphthol may have the potential to serve as a biomarker for PAH exposure, when smoking status is carefully adjusted. [ABSTRACT FROM AUTHOR]

Objectives Occupational coke oven emissions (COEs) have been considered an important health issue. However, there are no conclusive data on human hepatic injury due to COE exposure. The association of COE exposure with liver function was explored and the effects of modification of potential non-occupational factors were assessed. Methods 705 coke oven workers and 247 referents were investigated. Individual cumulative COE exposure was quantitatively estimated. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), γ-glutamyl transferase, alkaline phosphatase, hepatitis B surface antigen and anti-hepatitis C antibody were measured. Results Among those with high COE exposure, the adjusted ORs of abnormal ALT and AST were 5.23 (95% CI 2.66 to 10.27) and 1.95 (95% CI 1.18 to 3.52), respectively. Overweight individuals (body mass index (BMI) ≥25 kg/m²) with high COE exposure had elevated risks of abnormal ALT (adjusted OR 23.93, 95% CI 8.73 to 65.62) and AST (adjusted OR 5.18, 95% CI 2.32 to 11.58). Risk of liver damage in hepatitis B virus- or hepatitis C virus-positive individuals with COE exposure was also elevated. Conclusions Long-term exposure to COE increases the risk of liver dysfunction, which is more prominent among those with higher BMI and hepatitis virus infection. The risk assessment of liver damage associated with COE exposure should take BMI and hepatitis virus infection into consideration. [ABSTRACT FROM AUTHOR]

To investigate associations among occupational exposure to coke oven emissions (COEs), oxidative stress, cytogenotoxic effects, change in the metabolizing enzyme glutathione S-transferase (GST), and internal levels of polycyclic aromatic hydrocarbons (PAHs) in coke oven workers, we recruited 47 male coke oven workers and 31 male control subjects from a coke oven plant in northern China. We measured the levels of 1-hydroxypyrene (1-OHP) and 8-hydroxy-2'-deoxyguanosine (8-OHdG) in urine, micronucleated binucleated cells (BNMNs) in peripheral blood lymphocyte, and GST in serum. Our results showed that the group exposed to COEs had significantly increased levels of 1-OHP [median 5.7; interquartile range (IQR), 1.4-12.0 µmol/mol creatinine] compared with the control group (3; 0.5-6.4 µmol/mol creatinine). In addition, the median levels (IQR) of 8-OHdG, BNMNs, and GST were markedly increased in the exposed [1.9 (1.4-15.4) µmol/mol creatinine; 6 (2-8) per thousand; 22.1 (14.9-31.2) U/L, respectively] compared with controls [1.3 (1.0-4.0) µmol/mol creatinine, 2 (0-4) per thousand; and 13.1 (9.5-16.7) U/L, respectively]. These results appeared to be modified by smoking. However, multivariate logistic regression analysis revealed that exposure to COEs had the highest odds ratio among variables analyzed and that smoking was not a significant confounder of the levels of studied biomarkers. Overall, the present findings suggest that COE exposure led to increased internal PAH burden, genetic damage, oxidative stress, and GST activity. The consequences of the changes in these biomarkers, such as risk of cancer, warrant further investigations. [ABSTRACT FROM AUTHOR]

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., Competing Interests: No conflicts of interest reported., (Copyright and License information: Editorial Office of CCDCW, Chinese Center for Disease Control and Prevention 2022.)

In 1984, based on epidemiological data on cohorts of coke oven workers, USEPA estimated a unit risk for lung cancer associated with continuous exposure from birth to 1 Mug/m3 of coke oven emissions, of 6.2 X 10-4. This risk assessment was based on information on the cohorts available through 1966. Follow-up of these cohorts has now been extended to 1982 and, moreover, individual job histories, which were not available in 1984, have been constructed. In this study, lung cancer mortality in these cohorts of coke oven workers with extended follow-up was analyzed using standard techniques of survival analysis and a new approach based on the two stage clonal expansion model of carcinogenesis. The latter approach allows the explicitconsideration of detailed patterns of exposure of each individual inthe cohort. The analyses used the extended follow-up data through 1982 and the detailed job histories now available. Based on these analyses, the best estimate of unit risk is 1.5 X 10-4 with 95% confidence interval = 1.2 X 10-4 -1.8 X 10-4. [ABSTRACT FROM AUTHOR]

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. Image 1 • An association was shown between 1-OHP increasing and telomere length shortening. • An association was shown between 3-OHPhe increasing and telomere length shortening. • The biological exposure limit of 1-OHP was suggested at 0.40 μmol/mol creatinine. • The biological exposure limit of 3-OHPhe was suggested at 0.33 μmol/mol creatinine. [ABSTRACT FROM AUTHOR]

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. Image 1 • Coke oven emissions (COEs) exposure induced lower total antioxidant capacity (T-AOC). • A significant association was shown between COEs and T-AOC damage. • The occupational exposure limit of COEs was recommended at 0.03 mg/m3. [ABSTRACT FROM AUTHOR]

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. Image 1 • Urine 1-OHPYR was negatively related to telomere length. • Telomere length was associated with the total cumulative exposure dose. • Rs34413328 AA could slow down telomere shortening in the coke oven workers. [ABSTRACT FROM AUTHOR]

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&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., 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.

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. • Dose-response relationship was exhibited between the cumulative exposure dose of COEs and telomere damage. • The level of COEs exposure lower than the current exposure-limits might induce telomere damage in the coke oven workers. • To protect the health of coke oven workers, a stricter occupational exposure limit based on the BMDL of COEs obtained in this study can be established. [ABSTRACT FROM AUTHOR]