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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., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

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., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Conflict of interests No conflict of interest., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Existing evidence has showed that exposure to polycyclic aromatic hydrocarbons (PAHs) increases the risk of many chronic diseases. Given the close connection between aging (a major risk factor) and chronic diseases, however, very few studies have evaluated the association between PAHs and aging. Furthermore, whether modifiable healthy lifestyle could attenuate the detrimental effect of PAHs on aging remains unknown. Therefore, we conducted this study, aiming to: (1) examine the associations of urinary monohydroxy polycyclic aromatic hydrocarbons (OH-PAHs) and lifestyle with Phenotypic Age Acceleration (PhenoAge.Accel), a novel aging measure that captures morbidity and mortality risk; and (2) evaluate the potential interaction effects of OH-PAHs and lifestyle on PhenoAge.Accel. Cross-sectional data of 2,579 participants (aged 20-84 years, n = 1,292 females) from the National Health and Nutrition Examination Survey for years 2001-2010 were analyzed. A lifestyle index was constructed based on five components (drinking, smoking, body mass index, physical activity, and diet), ranging from 0 to 5. We calculated PhenoAge.Accel using algorithms developed previously. General linear regression models were used to examine the associations. We observed strong associations of OH-PAHs and lifestyle with PhenoAge.Accel. For instance, one unit increase in ∑NAP (sum of 1- and 2-hydroxynaphthalene) was associated with 0.37 year (95% confidence interval [CI]: 0.26, 0.48) increase in PhenoAge.Accel. We did not observe statistically significant interaction effects between OH-PAHs and lifestyle on PhenoAge.Accel. After stratified by sex, we observed strong associations as well as statistically significant interactions of OH-PAHs and lifestyle with PhenoAge.Accel among females. In conclusion, both OH-PAHs and lifestyle were independently associated with phenotypic aging and there were statistically significant interactions between OH-PAHs and lifestyle on phenotypic aging among females. The findings highlight the importance of adherence to a healthy lifestyle to attenuate the detrimental effects of exposures to PAHs on phenotypic aging among females., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Telomeres are functional complexes at the ends of linear chromosomes, and telomerase aids in their maintenance and replication. Additionally, accumulating evidence suggests that telomerase-associated protein 1 (TEP1) is a component of the telomerase ribonucleoprotein complex and is responsible for catalyzing the addition of new synthetic telomere sequences to chromosome ends. In our previous study, we found that genetic variants of the TERT gene participated in the regulation of telomere length. Exposure to particulate matter, environmental pollutants, oxidative stress, and pesticides is associated with shortening of telomere length. However, it is unknown whether genetic variants in the TEP1 gene may affect telomere length (TL) in polycyclic aromatic hydrocarbon (PAH)-exposed workers. Therefore, we measured the peripheral leukocyte TL and genotyped the polymorphism loci in the TEP1 gene among 544 PAH-exposed workers and 238 healthy controls. Covariance analysis showed that the individuals carrying TEP1 rs1760903 CC and TEP1 rs1760904 TT had longer TL in the control group (P < 0.05). In the generalized linear model, we found that rs1760903 CC was a protective factor against TL shortening, and PAH exposure could promote telomere shortening (P < 0.05). Thus, this study reinforces the roles of environmental factors and genetic variations in telomere damage, and provides a theoretical foundation for the early detection of susceptible populations and the establishment of occupational standards., (Copyright © 2021. Published by Elsevier Inc.)

Objectives: The aim was to explore the dose-response relationship between occupational polycyclic aromatic hydrocarbons (PAHs) exposure and mitochondrial damage in coke oven plants workers., Methods: 544 workers and 238 healthy people were recruited. The ultra-high performance liquid chromatography was used to determine the level of 1-hydroxypyrene, 1-hydroxynaphthalene, 2-hydroxynaphthalene and 3-hydroxyphenanthrene. The real-time fluorescence quantitative polymerase chain reaction was used to determine the mitochondrial DNA copy number (mtDNAcn). The benchmark dose software was used to analyze the benchmark dose., Results: The mtDNAcn in the exposure group was lower than that in the control group. The concentrations of 1-hydroxypyrene, 1-hydroxynaphthalene, 2-hydroxynaphthalene and 3-hydroxyphenanthrene in the exposure group were higher than those in the control group. There is a dose-response relationship between 1-hydroxypyrene, 3-hydroxyphenanthrene and mitochondrial DNA damage. The benchmark dose lower confidence limit (BMDL) of 1-hydroxypyrene were 0.045, 0.004, and 0.058 pg/μg creatinine in the total, male, and female population, respectively. The BMDL of 3-hydroxyphenanthrene were 5.142, 6.099, and 2.807 pg/μg creatinine in the total, male, and female population, respectively., Conclusions: The BMDL of 1-hydroxypyrene and 3-hydroxyphenanthrene initially explored can provide a reference to establish occupational exposure biological limits., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Polycyclic aromatic hydrocarbons (PAHs) exposure had been reported to be a risk factor of mtDNAcn in our early study. However, the effect of metabolic enzymes' genetic polymorphisms on mtDNAcn in PAHs-Exposure workers has not been fully evaluated., Aim: The aim of the study was to explore the effect of metabolic enzymes' genetic polymorphisms on mtDNAcn in PAHs-Exposure., Methods and Results: We investigated the effects of metabolic enzymes' genetic polymorphisms on mtDNAcn among 544 coke oven workers and 238 office staffs. The mtDNAcn of peripheral blood leukocytes was measured using the Real-time quantitative polymerase chain reaction (PCR) method. PCR and restriction fragment length was used to detect five polymorphisms in GSTT1, GSTM1, GSTP1 rs1695, CYP2E1 rs6413432, and CYP2E1 rs3813867. The mtDNAcn in peripheral blood leukocytes was significantly lower in the exposure group than that in the control group (p < .001). The 1-OHPYR had an increasing trend with the genotypes AA→AG → GG of GSTP1 rs1695 in the control group. Generalized linear model indicated that the influencing factors of mtDNAcn were PAHs-exposure [β (95% CI) = -0.420 (-0.469, -0.372), p < .001], male [β (95% CI) = -0.058 (-0.103, -0.012), p = .013], and AA genotype for GSTP1 rs1695 [β (95% CI) = -0.051 (-0.095, -0.008), p = .020]., Conclusion: The individuals carrying the AA genotype of GSTP1 rs1695 may have a lower mtDNAcn due to their weaker detoxification of PAHs., (© 2021 The Authors. Cancer Reports published by Wiley Periodicals LLC.)

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., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

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., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

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., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

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 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]