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Background: Preserved ratio impaired spirometry (PRISm) and airflow obstruction are recognized as critical early signs of chronic obstructive pulmonary disease (COPD). While these conditions arise from concurrent exposure to toxicants and essential nutrients, how vitamin D modifies the pulmonary toxicity induced by polycyclic aromatic hydrocarbons (PAHs) and the metabolic mechanisms involved is still unclear., Methods: Based on the National Health and Nutrition Examination Survey (NHANES) 2007-2012, data on urinary PAH metabolites (ΣOH-PAHs), serum vitamin D metabolite levels [Σ25(OH)D], and pulmonary function tests [forced expiratory volume in one second (FEV1), forced vital capacity (FVC) and FEV1/FVC] from 2189 participants, including 369 subjects with early lung dysfunction, defined as PRISm or airflow obstruction. Multiple metabolic disorder indicators were calculated using biochemical markers. The interaction effects between vitamin D and PAHs were evaluated using multiple linear and logistic regression models. Causal mediation analyses and structural equation modeling were employed to investigate the mediating roles of metabolic indicators., Results: PAHs and vitamin D had opposite effects on lung function parameters [FEV1: β (95 CIs) = -0.01 (-0.02, -0.01) vs. 0.01 (0.01, 0.04); FVC: β (95 CIs) = -0.01 (-0.02, 0.01) vs. 0.04 (0.01, 0.06)] and risk of early lung dysfunction [OR (95 CIs) = 1.22 (1.06, 1.40) vs. 0.52 (0.37, 0.73)]. Decreased associations of ΣOH-PAHs with FEV1, FVC, and early lung dysfunction, as well as with metabolic score-visceral adiposity index (MSV) were visualized with increased Σ25(OH)D among subjects with body mass index (BMI) < 28 kg/m 2 . Furthermore, 2.18 %, 18.20 %, 5.70 %, and 4.70 % of the associations of co-exposure to ΣOH-PAHs and Σ25(OH)D with FEV1, FVC, FEV1/FVC, and early lung dysfunction disease were mediated by MSV., Conclusions: Our findings indicated that vitamin D antagonizes the hazardous effects of PAHs on early lung dysfunction by metabolic alteration, providing new insight into the identification of the underlying high-risk populations and accessible prevention and intervention measures for attenuating PAH-induced lung dysfunction., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Yansen Bai reports financial support was provided by Guangzhou Medical University. If there are other authors, they 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 © 2024. Published by Elsevier Inc.)

Background: Polycyclic aromatic hydrocarbons (PAHs) are well-acknowledged pro-inflammatory chemicals, but their associations with blood cell-based inflammatory biomarkers need further investigation. Moreover, the effects and mechanisms of essential metals on PAH-related inflammation remain poorly understood., Objects: To elucidate the associations of PAHs on inflammatory biomarkers, as well as the effects and mechanisms of essential metals on these associations., Methods: A cross-sectional study was conducted on 1388 coke oven workers. We analyzed the modification effects of key essential metal(s) on PAHs-inflammatory biomarkers associations. To explore the possible mechanisms from an inflammation perspective, we performed a bioinformatic analysis on the genes of PAHs and essential metals obtained from the Comparative Toxicogenomics Database (CTD) and performed a mediation analysis., Results: We observed associations of PAHs and essential metals with lymphocyte-to-monocyte ratio (LMR) (P < 0.05). PAH mixtures were inversely associated with LMR (β QGC-index  = -0.18, P < 0.001), with 1-hydroxypyrene (1-OH-Pyr) being the most prominent contributor (weight = 63.37%), whereas a positive association between essential metal mixtures and LMR was observed (β QGC-index  = 0.14, P < 0.001), with tin being the most significant contributor (weight = 51.61%). An inverse association of 1-OH-Pyr with LMR was weakened by increased tin exposure (P < 0.05). The CTD database showed that PAHs and tin compounds co-regulated 22 inflammation-associated genes, but they regulated most genes in opposite directions. Further identified the involvement of oxidative stress and mediation analysis showed that the mediation effect of 8-hydroxydeoxyguanosine (8-OHdG) on 1-OH-Pyr-LMR association presented heterogeneity between low and high tin tertile groups (I 2  = 37.84%)., Conclusion: 1-OH-Pyr and tin were significantly associated with LMR. Modification effects indicated that the inverse association of 1-OH-Pyr with LMR was mitigated with an increase in tin. The mediation effect of 8-OHdG on the inverse association of 1-OH-Pyr with LMR may be partially dependent on tin., 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 © 2024 Elsevier Ltd. All rights reserved.)

Whether adopting healthy lifestyles and maintaining moderate levels of essential metals could attenuate the reduction of heart rate variability (HRV) related to polycyclic aromatic hydrocarbons (PAHs) exposure are largely unknown. In this study, we measured urinary metals and PAHs as well as HRV, and constructed a healthy lifestyle score in 1267 coke oven workers. Linear regression models were used to explore the association of healthy lifestyle score and essential metals with HRV, and interaction analysis was performed to investigate the potential interaction between healthy lifestyle score, essential metals, and PAHs on HRV. Mean age of the participants was 41.9 years (84.5% male). Per one point higher healthy lifestyle score was associated with a 2.5% (95% CI, 1.0%-3.9%) higher standard deviation of all normal to normal intervals (SDNN), 2.1% (95% CI, 0.5%-3.6%) higher root mean square of successive differences in adjacent NN intervals (r-MSSD), 4.3% (95% CI, 0.4%-8.2%) higher low frequency, 4.4% (95% CI, 0.2%-8.5%) higher high frequency, and 4.4% (95% CI, 1.2%-7.6%) higher total power, respectively. Urinary level of chromium was positively associated with HRV indices, with the corresponding β (95% CI) (%) was 5.17 (2.84, 7.50) for SDNN, 4.29 (1.74, 6.84) for r-MSSD, 12.26 (6.08, 18.45) for low frequency, 12.61 (5.87, 19.36) for high frequency, and 11.31 (6.19, 16.43) for total power. Additionally, a significant interaction was found between healthy lifestyle score and urinary total hydroxynaphthalene on SDNN (P interaction  = 0.04), and higher level of urinary chromium could attenuate the adverse effect of total hydroxynaphthalene level on HRV (all P interaction <0.05). Findings of our study suggest adopting healthy lifestyle and maintaining a relatively high level of chromium might attenuate the reduction of HRV related to total hydroxynaphthalene exposure., Competing Interests: Declaration of competing interest The authors declare they have no actual or potential conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier GmbH.. All rights reserved.)

Metabolic syndrome (MetS) prevalence has increased dramatically worldwide and has become a public health issue. Polycyclic aromatic hydrocarbons (PAHs) were identified as risk factors of MetS, while essential metals are integral parts of metalloenzymes catalyzing metabolic processes. However, effects of co-exposure to PAHs and essential metals have not been investigated yet. We aimed to assess whether essential metals could modify the hazard effects of PAHs on MetS, and underlying mediation effects of microRNA (miRNAs) were further explored. A cross-sectional study of 1451 males including 278 MetS cases was conducted. Internal exposure levels of 5 classes of PAH metabolites, 7 essential metals, as well as expressions of PAHs-associated 8 plasma miRNAs were assessed. Multiple exposure models, Bayesian kernel machine regression (BKMR), and quantile g-computation (QGcomp) were used simultaneously to identify MetS-related critical chemicals. Mutual effect modification between chemicals and mediation effects of miRNAs on chemical-MetS association was testified. In this study, hydroxyphenanthrene (OHPhe) and selenium (Se) were consistently identified as MetS-related key chemicals in three statistical methods. OHPhe was positively associated with MetS [OR (95 % CI) = 1.79 (1.21, 2.65), P = 0.004], while Se had a negative relationship with MetS [OR (95 % CI) = 0.61 (0.43, 0.87), P = 0.007]. Effect modification analysis observed the association between OHPhe and MetS was weakened with increased Se exposure. Only the expression of miR-24-3p was negatively associated with MetS [OR (95 % CI) = 0.81 (0.66, 0.95), P = 0.048] and could mediate 16.1 % of OHPhe-MetS association in subjects with low Se exposure (≤0.87 μg/mmol creatinine) (P = 0.019). We found a mutual effect modification between OHPhe and Se on MetS, and the positive OHPhe-MetS association was attenuated with increased Se exposure. Mediation effects of miR-24-3p on OHPhe-MetS association were dependent on Se dose. Our findings may provide new insight into the prevention and intervention of MetS., 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 B.V. All rights reserved.)

Mosaic loss of chromosome Y (mLOY) is an indicator of genome instability, but the environmental stressors of mLOY remained largely unknown. In this study, we detected the internal exposure levels of 11 polycyclic aromatic hydrocarbon (PAH) metabolites and 22 metals among 888 coke-oven workers, and calculated their blood mLOY based on genome-wide SNP genotyping data and presented as median log R ratio (mLRR-Y). The generalized linear model (GLM), LASSO, and Bayesian kernel machine regression (BKMR), were used to select mLOY-relevant chemicals. The results of these models consistently suggested the negative dose-response relationships of urinary 1-hydroxynaphthalene (1-OHNa), antimony (Sb), and molybdenum (Mo) with mLRR-Y. There were no pairwise interactions between these three chemicals (P interaction > 0.05), but subjects with high exposure to ≥ 2 kinds of these chemicals showed reducing mLRR-Y [β(95%CI) = - 0.015(- 0.023, - 0.008)], increasing oxidative DNA damage (marked by 8-hydroxydeoxyguanosine) [β(95%CI) = 0.625(0.454, 0.796)] and chromosome damage (marked by micronucleus frequency in lymphocytes) [frequency ratio (FR) and 95%CI = 1.146(1.047, 1.225)] than those with low exposure to all these chemicals. The combined effects of 1-OHNa, Sb, and Mo on elevating DNA damage may partly explain their joint effects on increased blood mLOY. These results provided a new insight into environmental hazards co-exposure on chromosome-Y deletions., (Copyright © 2021 Elsevier B.V. All rights reserved.)

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., (Copyright © 2020 Elsevier B.V. All rights reserved.)

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., Competing Interests: Declaration of competing interest The authors declare no competing financial interest., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Telomere length (TL) is an index of cellular aging and can predict the incidences of many age-related diseases. Change of TL might be affected by environmental pollution and individual's genetic background. In this cohort study, we aimed to evaluate the associations between polycyclic aromatic hydrocarbons (PAHs) exposure and longitudinal TL shortening, and investigate whether genetic variations in TERT-CLPTM1L can modify these associations. We measured the baseline concentrations of twelve urinary PAH metabolites and genotyped six variants at TERT-CLPTM1L among 1243 coke-oven workers. The relative leukocyte TL was detected in both baseline and follow-up (4 years later) visits. The TL shortening were estimated by TL decline and TL ratio. We found that the urinary level of 1-hydroxypyrene (1-OHP) had significant dose-response relationships with increased TL decline [β(95%CI) = 0.078(0.023, 0.133), P = 0.005] and TL ratio [β(95%CI) = 0.096(0.037, 0.155), P = 0.002]. Besides, urinary 1-hydroxynaphthalene (1-OHNa) was marginally dose-related with elevated TL decline [β(95%CI) = 0.053(-0.001, 0.107), P = 0.055] and TL ratio [β(95%CI) = 0.057(-0.002, 0.116), P = 0.058]. Analyses of TERT-CLPTM1L variants showed that the rs401681 and rs465498 could modify the effect of 1-OHP on increasing TL decline (P interaction  = 0.012 and 0.035, respectively) and TL ratio (P interaction  = 0.014 and 0.067, respectively), which were pronounced among rs401681TT and rs465498CC carriers, but not seen among rs401681TC + CC and rs465498CT + TT carriers. In conclusion, elevated exposure to PAHs can accelerate the TL shortening and this effect can be modified by TERT-CLPTM1L variants. These results may add potential evidence for gene-environment interactions on dynamic changes of telomere length. Further studies are warranted to validate these findings and uncover the underlying mechanisms., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: Aging is related to an increased risk of morbidity and mortality and is affected by environmental factors. Exposure to polycyclic aromatic hydrocarbons (PAHs) is associated with adverse health outcomes; but the association of such exposure with DNA methylation aging, a novel aging marker, is unclear., Objectives: Our aim was to investigate the association of PAH exposure with methylation aging., Methods: We trained and validated a methylation age predictor suitable for Chinese populations using whole blood methylation data in 989 Chinese and 160 Caucasians. We defined two aging indicators: δage, as methylation age minus chronological age; and aging rate, the ratio of methylation to chronological age. The association of PAH exposure with aging indicators was evaluated using linear regressions in three panels of healthy Chinese participants ( N =539, among the aforementioned 989 Chinese participants) whose exposure levels were assessed by 10 urinary monohydroxy-PAH metabolites., Results: We developed a methylation age predictor providing accurate predictions in both Chinese individuals and Caucasian persons (R=0.94-0.96, RMSE=3.8-4.3). Among the 10 urinary metabolites that we measured, 1-hydroxypyrene and 9-hydroxyphenanthrene were associated with methylation aging independently of other OH-PAHs and risk factors; 1-unit increase in 1-hydroxypyrene was associated with a 0.53-y increase in Δage [95% confidence interval (CI): 0.18, 0.88; false discovery rate (FDR) FDR =0.004] and 1.17% increase in aging rate (95% CI: 0.36, 1.98; FDR =0.02), whereas for 9-hydroxyphenanthrene, the increase was 0.54-y for Δage (95% CI: 0.17, 0.91; FDR =0.004), and 1.15% for aging rate (95% CI: 0.31, 1.99; FDR =0.02). The association direction was consistent across the three Chinese panels with the association magnitude correlating with the panels' exposure levels; the association was validated by methylation data of purified leukocytes. Several cytosine-phosphoguanines, including those located on FHL2 and ELOVL2 , were found associated with both aging indicators and monohydroxy-PAH levels., Conclusions: We developed a methylation age predictor specific for Chinese populations but also accurate for Caucasian populations. Our findings suggest that exposure to PAHs may be associated with an adverse impact on human aging and epigenetic alterations in Chinese populations. https://doi.org/10.1289/EHP2773.

Objectives: This study aimed to investigate quantitative relationships of urinary PAH metabolites with lung function declines among coke-oven workers., Methods: We performed a prospective investigation involving 1243 workers with follow-up periods from 2010 to 2014. Their lung function measurements, including forced vital capacity (FVC), forced expiratory volume in one second (FEV1), the percentage of predicted FVC (FVC%) and FEV1 (FEV1%), FEV1/FVC ratio, and forced expiratory flow between 25% and 75% of vital capacity (FEF25-75), were detected in both baseline (2010) and follow-up study (2014). We also detected the urinary concentrations of 12 PAH metabolites in the baseline study. The relationships between the baseline urinary PAH metabolites and 4-year lung function declines were analyzed by multivariate linear regressions, with adjustment for potential confounders., Results: We found that the baseline concentrations of urinary 1-hydroxynaphthalene (1-OHNa), 2-OHNa, 2-hydroxyfluorene (2-OHFlu), 9-OHFlu, 1-hydroxyphenanthrene (1-OHPh), 2-OHPh, and ΣOH-PAHs were significantly associated with accelerated decline in FEV1/FVC [all β>0 and false discovery rate (FDR) P<0.05]. Additionally, the baseline levels of urinary 1-OHNa, 1-OHPh, 2-OHPh, 9-OHPh, 1-hydroxypyrene (1-OHP), and ΣOH-PAHs were associated with significantly deeper decline in FEF25-75 (all β>0 and FDR P<0.10). When using backward selection to adjustment for 10 urinary PAH metabolites, the most significant determiner for FEV1/FVC decline was 1-OHNa among nonsmokers and 9-OHFlu among smokers, and the significant determiner for FEF25-75 decline was 9-OHPh among nonsmokers and 1-OHP among smokers., Conclusions: This longitudinal study revealed that higher baseline exposure levels of PAHs could lead to greater decline in lung function over a 4-year follow-up., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Essential metals play important roles in maintaining cellular homeostasis, but the effects of their interaction with the environmental pollutants are still not very well-known in human subjects. The aim of this study was to evaluate the roles of essential metals and their interactions with polycyclic aromatic hydrocarbons (PAHs) on chromosome damage, an early carcinogenic event. A total of 1245 male workers were included in this study and the levels of 11 urinary essential metals, 12 urinary PAH metabolites, plasma concentrations of benzo[a]pyrene-r-7,t-8,t-9,c-10-tetrahydotetrol-albumin (BPDE-Alb) adducts, and lymphocyte micronucleus (MN) frequencies were monitored. We found that zinc (Zn), selenium (Se), and strontium (Sr) have significant inverse dose-response relationships with MN frequencies (all P < 0.05). Furthermore, the protective roles of Zn, Se, and Sr were mainly shown among subjects with high levels of BPDE-Alb adducts. Significant effect modification of BPDE-Alb adducts on the associations of Zn, Se, and Sr with MN frequencies was observed (all Pinteraction < 0.05). Our study showed evidence that Zn, Se, and Sr play protective roles in reducing chromosome damage, and these effects can be modified by PAH exposure levels. These findings add potential evidence for the preventive effects of Zn, Se, and Sr against carcinogenesis in human subjects.

The article presents the study conducted on interaction of RARB variant with polycyclic aromatic hydrocarbon exposure on lung function. Topics of discussion includes studies suggest that genetic variants may imapct the association of air pollutants with respiratory results. Epidemiological studies also presents the relation between polycyclic aromatic hydrocarbon in air pollution on the altered lung function.

Arsenic (As) is an established toxic metal, but its effect on longitudinal lung function change among occupational workers is less conclusive. 1243 participants were recruited in a coke-oven plant and followed up from 2010 to 2014. Each individual provided 20 mL morning urine sample at baseline, which was then used for urinary levels of As (U–As) and polycyclic aromatic hydrocarbon (PAH) metabolites detecting. Lung function levels at both baseline and the end of follow-up were determined. Multiple linear regression models were used to analyze the associations between U–As with annual lung function changes, and to evaluate the joint effects of U–As with cigarette smoking and regular physical exercise. Among all participants, each 2-fold increase in U–As was associated with −12.09 (95%CI: −19.37, −4.81) mL, −0.32% (95%CI: −0.54%, −0.10%), −15.04 (95%CI: −24.62, −5.46) mL, and −0.36% (95%CI: −0.64%, −0.08%) annual changes in reduced forced expiratory volume in 1 second (FEV 1), percent predicted FEV 1 (ppFEV 1), forced vital capacity (FVC), and percent predicted FVC (ppFVC), respectively. These effects were more pronounced among coke-oven workers with smoking (especially heavy smoking with pack-years≥15) and without regular physical exercise. Compared to low-As-exposed (≤4.70 μg/mmol creatinine) non-smokers with regular physical exercise, the high-As-exposed (>4.70 μg/mmol creatinine) smokers without regular physical exercise had the worst annual declines in FEV 1 [β (95%CI) = −69.01 (−106.67, −31.34) mL], ppFEV 1 [β (95%CI) = −1.94% (−3.02%, −0.87%)], FVC [β (95%CI) = −78.66 (95%CI: −129.46, −27.86) mL], and ppFVC [β (95%CI) = −1.80% (−3.23%, −0.37%)]. The findings in our prospective cohort study suggested the positively linear dose-response relationship of U–As with annual lung function decline. The adverse effects of As could be enhanced by cigarette smoking and attenuated by regular physical exercise. Specific emphasizes on tobacco control and physical exercise were suggested to prevent As exposure induced pulmonary impairment. • Increased As exposure was associated with annual lung function reduction. • The adverse effect of As was particularly evident among smokers. • Physical exercise could attenuate the effect of As on reduced lung function. • High As, smoking, and non-regular exercise showed joint effects on lung impairment. [ABSTRACT FROM AUTHOR]