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Background: Exposure to polycyclic aromatic hydrocarbons (PAHs) is related to decreased lung function. However, whether oxidative damage is involved in this relationship remains unclear. This study was aimed to explore the potential mediating role of oxidative DNA or lipid damage in the association between PAH exposure and lung function., Methods: The urinary levels of monohydroxy polycyclic aromatic hydrocarbon metabolites (OH-PAHs) and lung function parameters were measured among 3367 participants from the baseline of the Wuhan-Zhuhai cohort. Urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) and 8-isoprostane (8-iso-PGF2α) were determined to evaluate the individuals' oxidative DNA and lipid damage degrees, respectively. Linear mixed models were used to investigate the associations of urinary OH-PAHs, 8-OHdG and 8-iso-PGF2α with lung function parameters. Mediation analysis was further conducted to assess the potential role of oxidative damage in the association between urinary OH-PAHs and lung function., Results: Each one-percentage increase in the sum of urinary OH-PAHs, high-molecular-weight or low-molecular-weight OH-PAHs (ƩOH-PAHs, ƩHMW OH-PAH or ƩLMW OH-PAHs, respectively) was associated with a 0.2152-, 0.2076- or 0.1985- ml decrease in FEV 1 , and a 0.1891-, 0.2195- or 0.1634- ml decrease in FVC, respectively. Additionally, significantly positive dose-response relationships of ƩOH-PAHs, ƩHMW OH-PAH and ƩLMW OH-PAHs with urinary 8-OHdG or 8-iso-PGF2α, as well as an inverse dose-response relationship between urinary 8-OHdG and FVC, were observed (all P for trend < 0.05). Mediation analysis indicated that urinary 8-OHdG mediated 14.22% of the association between ƩHMW OH-PAH and FVC., Conclusion: Higher levels of oxidative DNA damage might be involved in the decreased levels of FVC caused by high-molecular-weight PAH exposure.

Autophagy associated genes (ATGs) played an important role in the repair process of DNA damage and decreased autophagy may weaken the repair process and aggravate DNA damage. Based on this, we hypothesized that DNA damage levels might be modified by genetic variants in autophagy associated genes. In order to validate our hypothesis, 307 subjects were recruited from three different cities (Zhuhai, Wuhan and Tianjin) in China. Demographic data, individual 24-h PM 2.5 exposure and peripheral blood DNA damage levels were also detected. Seven potentially functional polymorphisms in four essential autophagy associated genes (ATG5, ATG7, ATG8 and ATG13) were screened to evaluate the relationship between the polymorphisms of autophagy associated genes and DNA damage levels. This association was assessed by using multivariable linear regression model, age, sex, smoke and PM 2.5 exposure levels were adjusted in each city. We found that rs12599322 in ATG8 (A>G, β=0.263, 95% CI: 0.108-0.419, P=8.98×10 -4 ) and rs7484002 in ATG13 (A>G, β=0.396, 95% CI: 0.085-0.708, P=0.013) were significantly associated with higher DNA damage levels. Furthermore, functional annotations showed that both rs12599322 and rs7484002 located at transcription factor binding sites (TFBS), indicating that they could regulate the expression of related genes through TF regulation. Following allelic trend analysis revealed that the DNA damage levels were significantly aggravated with the increasing number of risk variants in autophagy associated genes (P for trend: 8.09×10 -5 ). Our findings suggested that the polymorphisms in ATGs may influence DNA damage levels in one of the Chinese population., (Copyright © 2017. Published by Elsevier B.V.)

Aminoacyl-tRNA synthetases (ARSs) and ARS-interacting multi-functional proteins (AIMPs) form a multisynthetase complex (MSC) and play an important role in the process of DNA damage repair. We hypothesized that genetic variants in key ARSs and AIMPs might regulate the DNA damage response. Therefore, we systematically screened 23 potentially functional polymorphisms in MSC genes and evaluated the association between the genetic variants and DNA damage levels in 307 subjects from three cities in southern, central and northern China (Zhuhai, Wuhan and Tianjin, respectively). We examined personal 24-h PM2.5 exposure levels and DNA damage levels in peripheral blood lymphocytes for each subject. We found that the variant allele of rs12199241 in AIMP3 was significantly associated with DNA damage levels (β=0.343, 95%CI: 0.133-0.554, P=0.001). Meanwhile, the results of rs5030754 in EPRS and rs3784929 in KARS indicated their suggestive roles in DNA damage processes (β=0.331, 95%CI: 0.062-0.599, P=0.016 for rs5030754; β=0.192, 95%CI: 0.016-0.368, P=0.033 for rs3784929, respectively). After multiple testing, rs12199241 was still significantly associated with DNA damage levels. Combined analysis of these three polymorphisms showed a significant allele-dosage association between the number of risk alleles and higher DNA damage levels (Ptrend<0.001). These findings indicate that genetic variants in MSC genes may account for PM2.5-modulated DNA damage levels in Chinese populations., (Copyright © 2016. Published by Elsevier B.V.)

Exposure to particulate matter 2.5 (PM2.5) may result in DNA damage. Histone variant H2AX phosphorylation plays a central role in the response to damaged chromatin. In the current study, we investigated whether H2AX gene polymorphisms account for PM2.5-modulated DNA damage levels. A total of 307 healthy urban residents were collected from three cities in southern, central, and northern China, Zhuhai, Wuhan, and Tianjin, respectively. The dust mass concentrations of PM2.5 were detected by Gilian 5000 pumps, and the DNA damage levels were measured using comet assay. Seven potentially functional single nucleotide polymorphisms (SNPs) of H2AX gene were selected and genotyped by Illumina Infinium(®) BeadChip. We found that three SNPs (rs10790283 G > A, rs604714 C > A and rs7759 A > G) were significantly associated with DNA damage levels (adjusted P = 0.002, 0.018 and 0.027, respectively). Significant interactions (P < 0.05) were observed between certain genetic polymorphisms and PM2.5-modulated DNA damage levels. These results suggested that genetic variations of H2AX might be associated with the DNA damage levels in urban residents with different exposure to PM2.5. Further studies with large sample size in independent populations merit validating these findings., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Exposure to particulate matter (e.g., PM2.5) may result in DNA damage, a major culprit in mutagenesis and environmental toxicity. DNA damage levels may vary among individuals simultaneously exposed to PM2.5, however, the genetic determinants are still unclear. To explore whether PM2.5 exposure and genetic variants contribute to the alteration in DNA damage, we recruited 328 subjects from three independent cohorts (119 from Zhuhai, 123 from Wuhan and 86 from Tianjin) in southern, central and northern China with different PM2.5 exposure levels. Personal 24-h PM2.5 exposure levels and DNA damage levels of peripheral blood lymphocytes were evaluated. Genotyping were performed using Illumina Human Exome BeadChip with 241,305 single nucleotide variants (SNVs). The DNA damage levels are consistent with the PM2.5 exposure levels of each cohort. A total of 35 SNVs were consistently associated with DNA damage levels among the three cohorts with pooled P values less than 1.00×10(-3) after adjustment for age, gender, smoking status and PM2.5 exposure levels, of which, 18 SNVs together with gender and PM2.5 exposure levels were independent factors contributing to DNA damage. Gene-based test revealed 3 genes significantly associated with DNA damage levels (P=5.11×10(-3) for POLH, P=2.88×10(-3) for RIT2 and P=2.29×10(-2) for CNTN4). Gene ontology (GO) analyses indicated that the identified variants were significantly enriched in DNA damage response pathway. Our findings highlight the importance of genetic variation as well as personal PM2.5 exposure in modulating individual DNA damage levels., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

The switching defective/sucrose nonfermenting (SWI/SNF) related, matrix associated, actin dependent regulators of chromatin (SMARC) are components of human SWI/SNF like chromatin remodeling protein complexes, which are essential in the process of DNA damage repair. In this study, we hypothesized that genetic variants in SMARC genes may modify the capacity of DNA repair to damage. To test this hypothesis, we genotyped a total of 20 polymorphisms in five key SMARC genes (SMARCA5, SMARCC2, SMARCD1, SMARCD2, SMARCD3) to evaluate their associations with DNA damage levels in 307 subjects. The DNA damage levels were measured with comet assay. The multiple linear regression was used to assess the relationship between each polymorphism and DNA damage levels in additive model. We found that the genotypes of rs6857360 (β=0.23, 95% CI=0.06-0.40, P=0.008) in SMARCA5, rs6919 (β=0.20, 95% CI=0.05-0.34, P=0.008) and rs2727280 (β=0.18, 95% CI=0.04-0.33, P=0.013) in SMARCD2, and rs17173769 (β=-0.27, 95% CI=-0.52 to -0.01, P=0.045) in SMARCD3 were significantly associated with DNA damage levels. After combining these four polymorphisms, we found that the more unfavorable alleles the subjects carried, the heavier DNA damage they suffered, suggesting a locus-dosage effect between combined genotypes and DNA damage levels (P for trend=0.006). These findings suggest that genetic variants in SMARC genes may contribute the individual variations of DNA damage levels in Chinese population. Further larger and functional studies are warranted to confirm our findings., (Copyright © 2014. Published by Elsevier Ireland Ltd.)

Objectives: Coke oven emissions (COE) containing polycyclic aromatic hydrocarbons (PAHs) can induce both benzo[a]pyrene-r-7, t-8, t-9,c-10-tetrahydotetrol-albumin (BPDE-Alb) adducts and DNA damage. However, the relation between these biomarkers for early biological effects is not well documented in coke oven workers., Methods: In this study, the authors recruited 207 male workers exposed to COE and 102 controls not exposed to COE in the same steel plant in northern China. They measured BPDE-Alb adduct concentrations in plasma with reverse-phase high performance liquid chromatography and DNA damage in peripheral blood lymphocytes with alkaline comet assay., Results: The results showed that the median concentration of BPDE-Alb adducts in the exposed group (34.36 fmol/mg albumin) was significantly higher than that in the control group (21.90 fmol/mg albumin, p = 0.012). The mean Olive tail moment (Olive TM) of DNA damage in the exposed and control groups were 1.20 and 0.63, respectively (p = 0.000). Multivariate logistic regression analysis revealed that the odds ratio (OR) for BPDE-Alb adduct and Olive TM associated with the exposure were 1.72 (95% CI 1.06 to 2.81) and 1.96 (95% CI 1.20 to 3.19), respectively. These results show significant correlations between the concentrations of BPDE-Alb adduct and Olive TM levels in exposed group (r = 0.235, p = 0.001) but not in control group (r = 0.093, p = 0.353)., Conclusion: The results suggest that occupational exposure to COE may induce both BPDE-Alb adducts and DNA damage in the lymphocytes of coke oven workers and that these two markers are useful for monitoring exposure to COE in the workplace.

Accumulating evidence has shown that both DNA damage caused by the metabolites of polycyclic aromatic hydrocarbons (PAH) and genetic polymorphisms in PAH-metabolic genes contribute to individual susceptibility to PAH-induced carcinogenesis. However, the functional relevance of genetic polymorphisms in PAH-metabolic genes in exposed individuals is still unclear. In this study of 240 coke-oven workers (the exposed group) and 123 non-coke-oven workers (the control group), we genotyped for polymorphisms in the AhR, CYP1A1, GSTM1, and GSTT1 genes by PCR methods, and determined the levels of DNA damage in peripheral blood lymphocytes using the alkaline comet assay. We found that the ln-transformed Olive tail moment (Olive TM) values in the exposed group were significantly higher than those in the control group (P < 0.001). Furthermore, in the exposed group, the Olive TM values in subjects with the AhR Lys(554) variant genotype were higher than those with the AhR Arg(554)/Arg(554) genotype (P = 0.021). Similarly, the Olive TM values in the non-coke-oven workers with the CYP1A1 MspI CC + CT genotype were lower than the values of those with the CYP1A1 MspI TT genotype (P = 0.005). However, these differences were not evident for GSTM1 and GSTT1. These results suggested that the polymorphism of AhR might modulate the effects of PAHs in the exposed group; however, the underlying molecular mechanisms by which this polymorphism may have affected the levels of PAH-induced DNA damage warrant further investigation.

Toxicologic studies have reported propylene oxide (PO) exposure may harm the respiratory system, but the association between PO exposure and lung function and potential mechanism remains unclear. What is the association between PO exposure and lung function and potential mediating mechanism? Urinary PO metabolite [N-Acetyl-S-(2-hydroxypropyl)-L-cysteine (2HPMA)] as PO internal exposure biomarker and lung function were measured for 3,692 community residents at baseline and repeated at 3-year follow up. Cross-sectional and longitudinal associations between urinary 2HPMA and lung function were assessed by linear mixed model. Urinary 8-hydroxy-deoxyguanosine, urinary 8-iso-prostaglandin-F2α, and plasma protein carbonyls as biomarkers of oxidative DNA damage, lipid peroxidation, and protein carbonylation, respectively, were measured for all participants to explore their potential roles in 2HPMA-associated lung function decline by mediation analysis. After adjustment for potential covariates, each threefold increase in urinary 2HPMA was cross sectionally associated with a 26.18 mL (95% CI, −50.55 to −1.81) and a 21.83 mL (95% CI, −42.71 to −0.95) decrease in FVC and FEV 1 , respectively, at baseline (all P <.05). After 3 years of follow up, 2HPMA was observed to be longitudinally associated with FEV 1 /FVC decline. No significant interaction effect of smoking or passive smoking was observed (P interaction >.05), and the associations between 2HPMA and lung function indexes were persistent among participants who were not smoking and those who were not passive smoking in both baseline and follow-up evaluations. We observed urinary 8-hydroxy-deoxyguanosine partially mediated the associations of 2HPMA with FVC (mediation proportion, 5.48%) and FEV 1 (mediation proportion, 6.81%), and plasma protein carbonyl partially mediated the association between 2HPMA and FEV 1 (mediation proportion, 3.44%). PO exposure was associated with lung function decline among community residents, and oxidative DNA damage and protein carbonylation partially mediated PO exposure-associated lung function decline. Further attention on respiratory damage caused by PO exposure is warranted. [ABSTRACT FROM AUTHOR]

Objective: Acrylamide exposure from daily-consumed food has raised global concern. We aimed to assess the exposure-response relationships of internal acrylamide exposure with oxidative DNA damage, lipid peroxidation, and fasting plasma glucose (FPG) alteration and investigate the mediating role of oxidative DNA damage and lipid peroxidation in the association of internal acrylamide exposure with FPG.Research Design and Methods: FPG and urinary biomarkers of oxidative DNA damage (8-hydroxy-deoxyguanosine [8-OHdG]), lipid peroxidation (8-iso-prostaglandin-F2α [8-iso-PGF2α]), and acrylamide exposure (N-acetyl-S-[2-carbamoylethyl]-l-cysteine [AAMA], N-acetyl-S-[2-carbamoyl-2-hydroxyethyl]-l-cysteine [GAMA]) were measured for 3,270 general adults from the Wuhan-Zhuhai cohort. The associations of urinary acrylamide metabolites with 8-OHdG, 8-iso-PGF2α, and FPG were assessed by linear mixed models. The mediating roles of 8-OHdG and 8-iso-PGF2α were evaluated by mediation analysis.Results: We found significant linear positive dose-response relationships of urinary acrylamide metabolites with 8-OHdG, 8-iso-PGF2α, and FPG (except GAMA with FPG) and 8-iso-PGF2α with FPG. Each 1-unit increase in log-transformed level of AAMA, AAMA + GAMA (ΣUAAM), or 8-iso-PGF2α was associated with a 0.17, 0.15, or 0.23 mmol/L increase in FPG, respectively (P and/or P trend < 0.05). Each 1% increase in AAMA, GAMA, or ΣUAAM was associated with a 0.19%, 0.27%, or 0.22% increase in 8-OHdG, respectively, and a 0.40%, 0.48%, or 0.44% increase in 8-iso-PGF2α, respectively (P and P trend < 0.05). Increased 8-iso-PGF2α rather than 8-OHdG significantly mediated 64.29% and 76.92% of the AAMA- and ΣUAAM-associated FPG increases, respectively.Conclusions: Exposure of the general adult population to acrylamide was associated with FPG elevation, oxidative DNA damage, and lipid peroxidation, which in turn partly mediated acrylamide-associated FPG elevation. [ABSTRACT FROM AUTHOR]

Abstract Objective Association of oxidative DNA damage with gain in anthropometric indices has not been fully elucidated. Methods In this study, participants (n = 1151) were derived from the baseline visit of Wuhan residents in the Wuhan-Zhuhai Cohort Study. The participants finished the physical examinations at both baseline and 3-year follow up. Urinary levels of 8-hydroxydeoxyguanosine (8-OHdG) were measured by gradient-elution high performance liquid chromatography method and then calibrated by urinary creatinine (Cr) values. Results Generalized linear models showed that after adjusted for confounding factors, baseline central obesity individuals with a ≥2.5% hip circumference (HC) loss or >5% HC gain had a 0.290 μmol/mol Cr (95% confidence interval (CI): 0.108, 0.472) or 0.553 μmol/mol Cr (95% CI: 0.273, 0.833) increase in urinary 8-OHdG levels compared with those with a −2.5%–2.5% HC gain (both P < 0.05). Moreover, compared with non-central obesity at both baseline and 3-year follow-up, we observed that central obese men at both baseline and 3-year follow-up had a 0.46 μmol/mol Cr (95% CI: 0.16, 0.75) increased in urinary 8-OHdG levels. Conclusions HC gain showed dose-dependent associations with urinary 8-OHdG levels. Moreover, male central obesity at both baseline and 3-year follow-up had an increased risk for urinary 8-OHdG levels. Highlights • Adults with ≥2.5% HC loss increased urinary 8-OHdG levels. • Baseline central obesity with >5% HC gain was at higher risk of increasing 8-OHdG. • Developed central obesity during the 3-year follow-up had higher urinary 8-OHdG. [ABSTRACT FROM AUTHOR]

Indoor air pollutants from environmental tobacco smoke and cooking fume can induce oxidative stress and inflammatory response, which generate oxidatively damaged DNA in human body. Among 2224 adults, levels of FENO and urinary 8-oxodG were measured using a nano coulomb nitric oxide analyzer and a high performance liquid chromatography system with electrochemical detector, respectively. Association between aging with higher FENO levels and urinary 8-oxodG levels were analyzed using multiple linear regression analysis. Nonsmoking women aged 64 years and over, with higher FENO (≥ 25 part per billion) and self-catering but without passive smoking had a higher risk of increased urinary 8-oxodG (△% of urinary 8-oxodG: 81.3 %, 95 % CI: 27.4-158.0 %) levels, particularly these elderly women with using liquefied petroleum gas for cooking, had a higher risk for increased urinary 8-oxodG levels (△% of urinary 8-oxodG: 100.2 %, 95 % CI: 95 % CI: 35.3-196.3 %), compared with those aged less than 64 years, with lower FENO (< 25 part per billion). Cooking activity aggravated aging-related the aging-induced in urinary 8-oxodG excretion among nonsmoking women aged 64 years and over but without passive smoking. [ABSTRACT FROM AUTHOR]

1-bromopropane is a US Environmental Protection Agency-identified significant hazardous air pollutant with concerned adverse respiratory effect. We aimed to investigate the relationship between 1-bromopropane exposure and pulmonary function and the underlying role of oxidative damage, which all remain unknown. Pulmonary function and urinary biomarkers of 1-bromopropane exposure (N-Acetyl-S-(n-propyl)-L-cysteine, BPMA) and oxidative damage to DNA (8-hydroxy-deoxyguanosine, 8-OHdG) and lipid (8-iso-prostaglandin-F2α, 8-iso-PGF2α) were measured for 3259 Chinese urban adults from the Wuhan-Zhuhai cohort. The cross-sectional relationship of BPMA with pulmonary function and the joint relationship of BPMA and 8-OHdG or 8-iso-PGF2α with pulmonary function were investigated by linear mixed models. The mediating roles of 8-OHdG and 8-iso-PGF2α were evaluated by mediation analysis. Additionally, a panel of 138 subjects was randomly convened from the same cohort to evaluate the stability of BPMA repeatedly measured in urine samples collected over consecutive three days and intervals of one, two, and three years, and to estimate the longitudinal relationship of BPMA with pulmonary function change in three years. We found each 3-fold increase in BPMA was cross-sectionally related to FVC and FEV 1 reductions by 29.88-mL and 25.67-mL, respectively (all P < 0.05). Joint relationship of BPMA and 8-OHdG rather than 8-iso-PGF2α with reduced pulmonary function was observed. Moreover, 8-OHdG significantly mediated 9.44% of the BPMA-related FVC reduction. Findings from the panel revealed a fair to excellent stability (intraclass correlation coefficient: 0.43–0.79) of BPMA in repeated urines collected over a period of three years. Besides, BPMA was longitudinally related to pulmonary function reduction in three years: compared with subjects with persistently low BPMA level, those with persistently high BPMA level had 79.08-mL/year and 49.80-mL/year declines in FVC and FEV 1 , respectively (all P < 0.05). Conclusively, 1-bromopropane exposure might impair pulmonary function of urban adult population, and oxidative DNA damage might be a potential mechanism underlying 1-bromopropane impairing pulmonary function especially FVC. [Display omitted] • BPMA was cross-sectionally associated with decreased pulmonary function. • BPMA was longitudinally associated with pulmonary function decline in 3 years. • 8-OHdG partly mediated BPMA-associated pulmonary function reduction. [ABSTRACT FROM AUTHOR]

Whether propylene oxide (PO) exposure is associated with hyperglycemia were rarely explored. We aimed to determine the relationship between PO exposure and glucose metabolism, and potential role of oxidative stress. Among 3294 Chinese urban adults, urinary PO metabolite (N-Acetyl-S-(2-hydroxypropyl)-L-cysteine, 2HPMA), biomarkers of oxidative DNA damage (8-oxo-7,8-dihydro-20-deoxyguanosine, 8-OHdG) and lipid peroxidation (8-isoprostane, 8-iso-PGF 2α) in urine were determined. The associations of 2HPMA with 8-OHdG, 8-iso-PGF 2α , fasting plasma glucose (FPG), and risk of diabetes were explored. The roles of 8-OHdG and 8-iso-PGF 2α on association of 2HPMA with FPG and risk of diabetes were detected. After adjusted for potential confounders, each 1-unit increase in log-transformed concentration of 2HPMA was associated with a 0.15-mmol/L increase in FPG level, and the adjusted OR (95% CI) of diabetes by the associations of log-transformed urinary 2HPMA concentrations was 1.47 (95% CI : 1.03–2.11). Combination effects of 2HPMA with 8-OHdG or 8-iso-PGF 2α on risk of diabetes were detected, and elevated 8-iso-PGF 2α significantly mediated 34.5% of the urinary 2HPMA-associated FPG elevation. PO exposure was positively associated with FPG levels and risk of diabetes. PO exposure combined with DNA oxidative damage or lipid peroxidation may increase the risk of diabetes, and lipid peroxidation may partially mediate the PO exposure-induced FPG elevation. [Display omitted] • Individual PO internal exposure was evaluated in general population. • PO was significantly associated with FPG and risk of diabetes. • Both 8-OHdG and 8-iso-PGF 2α combined with PO exposure increased diabetes risk. • 8-iso-PGF 2α might mediate the association between PO exposure and FPG elevation. [ABSTRACT FROM AUTHOR]

Polychlorinated dibenzo-dioxins and polychlorinated dibenzo-furans (PCDD/Fs) have been reported to induce reactive oxygen species and oxidative stress, but the dose-response relationships have not been explored in molecular epidemiological studies. In this study, a total of 602 participants were recruited, comprising of 215 foundry workers, 171 incineration workers and 216 residents living more than 5 km away from the plants as the reference group. Individual PCDD/Fs exposures were estimated according to PCDD/Fs levels of working and living ambient air and daily foods. Urinary 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodG) and 8-iso-prostaglandin-F2α (8-isoPGF2α) were determined to reflect oxidatively generated damage to DNA and lipid. Generalized linear models were used to access the associations between PCDD/Fs exposure and oxidative stress biomarkers. We found that PCDD/Fs exposure and urinary oxidative stress biomarkers of workers were all higher than those of the reference group. Significantly positive exposure-response relationships between individual PCDD/Fs exposures and urinary 8-oxodG and 8-iso-PGF2α were found. Each 1-unit increase in ln-transformed levels of PCDD/Fs exposure generated a 0.78 nmol/mmol creatinine increase in ln-transformed 8-oxodG and a 0.50 ng/mmol creatinine increase in ln-transformed 8-isoPGF2α in foundry workers, a 0.49 nmol/mmol creatinine increase in ln-transformed 8-oxodG and a 0.26 ng/mmol creatinine increase in ln-transformed 8-isoPGF2α in incineration workers, compared with the reference group. And such associations were not modified by tobacco use. Our findings could help to understand the dose-response relationships between PCDD/Fs and oxidatively generated damage to DNA and lipid, and provide an epidemiologic basis for conducting research on the carcinogenesis and other toxicity mechanisms of PCDD/Fs. Image 1 • PCDD/Fs levels were measured in both air and food samples. • Individual PCDD/Fs exposure of workers and residents was estimated. • Dose-response relationships between PCDD/Fs exposure and urinary 8-oxodG and 8-iso-PGF2α levels were explored in foundry and incineration workers respectively. • PCDD/Fs exposure associated with oxidative stress levels in both smokers and nonsmokers. [ABSTRACT FROM AUTHOR]

Previous publications have indicated that some metals are associated with an increased prevalence of type 2 diabetes mellitus (T2DM); however, the mechanisms remain largely unknown. This study aimed to quantify the associations of oxidative DNA damage with urinary metals and prevalence of T2DM among the general population, and further to assess the role of oxidative DNA damage in mediating the association of urinary metals with prevalence of T2DM. Diagnoses of T2DM were performed clinically or by measuring fasting levels of plasma glucose ≥7.0 mmol/L. Concentrations of urinary metals and 8-hydroxy-2′-deoxyguanosine (8-OHdG) in 2127 participants were measured using inductively coupled plasma-mass spectrometry and high-performance liquid chromatography. Relationships among urinary metals, 8-OHdG (a biomarker for oxidative DNA damage), and prevalence of T2DM were analyzed using mediation analysis. After adjusting for covariates, we found that the log-transformed levels of urinary copper, arsenic, selenium, molybdenum, and antimony were positively associated with prevalence of T2DM. Urinary 8-OHdG was not only positively correlated with copper, arsenic, selenium, and antimony in an upwardly trending, dose-responsive manner but was also positively associated with prevalence of T2DM (odds ratio (OR): 1.95; 95% CI: 1.17–3.24). Mediation analysis estimated that urinary 8-OHdG mediated 13.22% and 8.84% of associations between prevalence of T2DM and concentrations of urinary arsenic and antimony, respectively (all P value < 0.05). Our findings suggested that urinary arsenic and antimony concentrations were associated with an increased prevalence of T2DM by a mechanism partly involving oxidative DNA damage. [ABSTRACT FROM AUTHOR]

Autophagy associated genes (ATGs) played an important role in the repair process of DNA damage and decreased autophagy may weaken the repair process and aggravate DNA damage. Based on this, we hypothesized that DNA damage levels might be modified by genetic variants in autophagy associated genes. In order to validate our hypothesis, 307 subjects were recruited from three different cities (Zhuhai, Wuhan and Tianjin) in China. Demographic data, individual 24-h PM 2.5 exposure and peripheral blood DNA damage levels were also detected. Seven potentially functional polymorphisms in four essential autophagy associated genes ( ATG5 , ATG7 , ATG8 and ATG13 ) were screened to evaluate the relationship between the polymorphisms of autophagy associated genes and DNA damage levels. This association was assessed by using multivariable linear regression model, age, sex, smoke and PM 2.5 exposure levels were adjusted in each city. We found that rs12599322 in ATG8 (A > G, β = 0.263, 95% CI: 0.108–0.419, P = 8.98 × 10 − 4 ) and rs7484002 in ATG13 (A > G, β = 0.396, 95% CI: 0.085–0.708, P = 0.013) were significantly associated with higher DNA damage levels. Furthermore, functional annotations showed that both rs12599322 and rs7484002 located at transcription factor binding sites (TFBS), indicating that they could regulate the expression of related genes through TF regulation. Following allelic trend analysis revealed that the DNA damage levels were significantly aggravated with the increasing number of risk variants in autophagy associated genes ( P for trend: 8.09 × 10 − 5 ). Our findings suggested that the polymorphisms in ATGs may influence DNA damage levels in one of the Chinese population. [ABSTRACT FROM AUTHOR]

[Display omitted] • Urinary acrolein metabolites (UAMs) were repeatedly measured over a period of 3 years. • UAMs were cross-sectionally associated with pulmonary function (PF) reduction. • UAMs were longitudinally associated with PF decline in 3 years. • 8-OHdG, CRP, and CC16 aggravated and/or mediated acrolein-associated PF reduction. • This is the first study to report the associations of UAMs with PF. Acrolein is a significant high priority hazardous air pollutant with pulmonary toxicity and the leading cause of most noncancer adverse respiratory effects among air toxics that draws great attention. Whether and how acrolein exposure impacts pulmonary function remain inconclusive. To assess the association of acrolein exposure with pulmonary function and the underlying roles of oxidative DNA damage, inflammation, and pulmonary epithelium integrity. Among 3,279 Chinese adults from the Wuhan-Zhuhai cohort, associations of urinary acrolein metabolites (N-Acetyl-S-(2-carboxyethyl)-L-cysteine, CEMA; N-Acetyl-S-(3-hydroxypropyl)-L-cysteine, 3HPMA) as credible biomarkers of acrolein exposure with pulmonary function were analyzed by linear mixed models. Joint effects of biomarkers of oxidative DNA damage (8-hydroxy-deoxyguanosine), inflammation (C-reactive protein, CRP), and pulmonary epithelium integrity (Club cell secretory protein, CC16) with acrolein metabolites on pulmonary function and the mediating roles of these biomarkers were assessed. Besides, a subgroup (N = 138) was randomly recruited from the cohort to assess the stabilities of acrolein metabolites and their longitudinal associations with pulmonary function change in three years. Significant inverse dose–response relationships between acrolein metabolites and pulmonary function were found. Each 10-fold increment in CEMA, 3HPMA, or ΣUACLM (CEMA + 3HPMA) was cross-sectionally related to a 68.56-, 40.98-, or 46.02-ml reduction in FVC and a 61.54-, 43.10-, or 50.14-ml reduction in FEV 1 , respectively (P < 0.05). Furthermore, acrolein metabolites with fair to excellent stabilities were found to be longitudinally associated with pulmonary function decline in three years. Joint effects of acrolein metabolites with 8-hydroxy-deoxyguanosine, CRP, and CC16 on pulmonary function were identified. CRP significantly mediated 5.97% and 5.51% of CEMA-associated FVC and FEV 1 reductions, respectively. 8-hydroxy-deoxyguanosine significantly mediated 6.78%, 6.88%, and 7.61% of CEMA-, 3HPMA-, and ΣUACLM-associated FVC reductions, respectively. Acrolein exposure of general adults was cross-sectionally and longitudinally related to pulmonary function decline, which was aggravated and/or partly mediated by oxidative DNA damage, inflammation, and pulmonary epithelium injury. [ABSTRACT FROM AUTHOR]

• The FVC and FEV 1 levels were inversely correlated with PCDD/Fs exposure levels. • Urinary 8-OHdG levels were inversely correlated with lung function parameters. • Urinary 8-OHdG mediated the associations of PCDD/Fs exposure with FVC levels. • Urinary 8-OHdG mediated the associations of serum PCDD/Fs with FVC and FEV 1 levels. The lung has been reported to be one of the target organs of polychlorinated dibenzo-dioxins and polychlorinated dibenzo-furans (PCDD/Fs) in many toxicological studies. While the associations between PCDD/Fs exposure and lung function levels have not been investigated thoroughly. This study aimed to explore these associations and the potential mediating role of oxidative stress. In this study, 201 foundry workers and 222 non-exposed general residents were recruited from central China, and their lung function parameters were measured. Air and food samples were collected to determine the PCDD/Fs levels for individual PCDD/Fs exposure estimation. Serum PCDD/Fs levels were determined in a subgroup of individuals randomly selected from the study population to reflect the body burden. It was found that each 1-unit increase in ln-transformed concentration of PCDD/Fs exposure (fg TEQ/bw/day) was associated with a 0.47 L decrease in FVC and a 0.25 L decrease in FEV 1. Each 1-unit increase in ln-transformed concentration of serum PCDD/Fs (fg TEQ/g lipid) was associated with a 0.36 L decrease in FVC and a 0.24 L decrease in FEV 1. Urinary 8-hydroxy-2′-deoxyguanosine (8-OHdG) was not only positively related to PCDD/Fs exposure, but also inversely associated with FVC and FEV 1 are FVC (β = −0.15, 95% CI: −0.22 to −0.08) and FEV 1 (β = −0.07, 95% CI: −0.13 to −0.02). Mediation analysis revealed that urinary 8-OHdG mediated 12.22% of the associations of external PCDD/Fs exposure with FVC levels, 28.61% and 27.87% of the associations of serum PCDD/Fs with FVC and FEV 1 levels respectively. Our findings suggested that PCDD/Fs exposure was associated with decreased lung function levels by a mechanism partly involving oxidatively generated damage to DNA. [ABSTRACT FROM AUTHOR]