Biomarker Of Polycyclic Aromatic Hydrocarbons Exposure Research Articles

A multigenerational study can detect the evolutionary response to BaP exposure in the non-biting freshwater midge Chironomus riparius

The release of polycyclic aromatic hydrocarbons (PAHs) into the environment is posing a threat to ecosystems and human health. Benzo(a)pyrene (BaP) is considered a biomarker of PAH exposure and is classified as a Group 1 carcinogen. However, it was not known whether BaP is mutagenic, i.e. induces inherited germline mutations. In this study, we used a recently established method, which combines short-term mutation accumulation lines (MAL) with whole genome sequencing (WGS) to assess mutagenicity in the non-biting midge Chironomus riparius. The mutagenicity analysis was supplemented by an evaluation of the development of population fitness in three successive generations in the case of chronic exposure to BaP at a high concentration (100 μg/L). In addition, the level of ROS-induced oxidative stress was examined in vivo. Exposure to the higher BaP concentration led to an increase in germline mutations relative to the control, while the lower concentration showed no mentionable effect. Against expectations, BaP exposure decreased ROS-level compared to the control and is thus probably not responsible for the increased mutation rate. Likewise, the higher BaP concentration decreased fitness measured as population growth rate per day (PGR) significantly over all generations, without signs of rapid evolutionary adaptations. Our results thus highlighted that high BaP exposure may influence the evolutionary trajectory of organisms.

Urinary Metabolites of Polycyclic Aromatic Hydrocarbons of Rural Population in Northwestern China: Oxidative Stress and Health Risk Assessment.

Polycyclic aromatic hydrocarbon (PAH) exposure is suspected to be linked to oxidative damage. Herein, ten PAH human exposure biomarkers [hydroxylated PAH metabolites (OH-PAHs)] and five oxidative stress biomarkers (OSBs) were detected in urine samples collected from participants living in a rural area (n = 181) in Northwestern China. The median molar concentration of ΣOH-PAHs in urine was 47.0 pmol mL-1. The 2-hydroxynaphthalene (2-OHNap; median: 2.21 ng mL-1) was the dominant OH-PAH. The risk assessment of PAH exposure found that hazard index (HI) values were <1, indicating that the PAH exposure of rural people in Jingyuan would not generate significant cumulative risks. Smokers (median: 0.033) obtained higher HI values than nonsmokers (median: 0.015, p < 0.01), suggesting that smokers face a higher health risk from PAH exposure than nonsmokers. Pearson correlation and multivariate linear regression analysis revealed that ΣOH-PAH concentrations were significant factors in increasing the oxidative damage to deoxyribonucleic acid (DNA) (8-hydroxy-2'-deoxyguanosine, 8-OHdG), ribonucleic acid (RNA) (8-oxo-7,8-dihydroguanine, 8-oxoGua), and protein (o, o'-dityrosine, diY) (p < 0.05). Among all PAH metabolites, only 1-hydroxypyrene (1-OHPyr) could positively affect the expression of all five OSBs (p < 0.05), suggesting that urinary 1-OHPyr might be a reliable biomarker for PAH exposure and a useful indicator for assessing the impacts of PAH exposure on oxidative stress. This study is focused on the relation between PAH exposure and oxidative damage and lays a foundation for the study of the health effect mechanism of PAHs.

Polymorphisms in gene UGT1A1 modify the association of prenatal exposure to polycyclic aromatic hydrocarbons with congenital heart diseases risk

Introduction Prenatal exposure to polycyclic aromatic hydrocarbons (PAHs) is a risk factor for the occurrence of congenital heart diseases (CHDs). Genetic susceptibility to PAHs metabolism may modify the exposure–risk relationship. The role of uridine diphosphoglucuronosyl transferase 1A1 (UGT1A1) genetic polymorphisms for modulating the impacts of prenatal PAHs exposure on the risk of CHDs remains to be discovered. Objective The aim of this study was to investigate whether maternal UGT1A1 genetic polymorphisms are associated with fetal susceptibility to CHDs and to assess whether the risk is modified by maternal PAHs exposure. Methods Maternal urinary biomarker of PAHs exposure was determined in 357 pregnant women with CHDs fetuses and 270 controls (pregnant women carrying fetuses without major congenital malformations). Urinary 1-hydroxypyrene-glucuronide (1-OHPG) concentration, a sensitive biomarker for PAHs exposure, was measured using ultra-high-performance liquid chromatography coupled with tandem mass spectrometry. Maternal single nucleotide polymorphisms (SNPs) in UGT1A1, including rs3755319, rs887829, rs4148323, rs6742078, and rs6717546, were genotyped using an improved multiplex ligation detection reaction (iMLDR) technique. Unconditional logistic regression was performed to determine the impacts of UGT1A1 polymorphisms on the risks of CHDs and their subtypes. Generalized multifactor dimensionality reduction (GMDR) was used to analyze the gene–gene and gene–PAHs exposure interactions. Results None of the selected UGT1A1 polymorphisms was independently associated with the risk of CHDs. The interaction between SNP rs4148323 and PAHs exposure was observed to be associated with CHDs (p< .05). Pregnant women with high-level PAHs exposure and rs4148323 had an increased risk of carrying CHDs fetuses (GA-AA vs. GG: aOR = 2.00, 95% CI = 1.06–3.79). Moreover, the joint effect of rs4148323 and PAHs exposure was found to be significantly associated with risks of septal defects, conotruncal heart defects, and right-sided obstructive malformations. Conclusions Maternal genetic variations of UGT1A1 rs4148323 may modify the association between prenatal PAHs exposure and CHDs risk. This finding needs to be further confirmed in a larger-scale study.

Effects of H19/SAHH/DNMT1 on the oxidative DNA damage related to benzo[a]pyrene exposure.

The mechanisms that long noncoding RNA (lncRNA) H19 binding to S-adenosylhomocysteine hydrolase (SAHH) interacted with DNA methyltransferase 1 (DNMT1) and then regulated DNA damage caused by polycyclic aromatic hydrocarbons (PAHs) remain unclear. A total of 146 occupational workers in a Chinese coke-oven plant in 2014 were included in the final analyses. We used high-performance liquid chromatography mass spectrometry (HPLC-MS) equipped to detect urine biomarkers of PAHs exposure, including 2-hydroxynaphthalene (2-NAP), 2-hydroxyfluorene (2-FLU), 9-hydroxyphenanthrene (9-PHE) and 1-hydroxypyrene (1-OHP). The levels of SAM and SAH in plasma were detected by HPLC-ultraviolet. By constructing various BEAS-2B cell models exposed to 16μM benzo[a]pyrene (BaP) for 24h, toxicological parameters reflecting distinct mechanisms were evaluated. We documented that urinary 1-hydroxypyrene (1-OHP) levels were positively associated with blood H19 RNA expression (OR: 1.51, 95% CI: 1.03-2.19), but opposite to plasma SAHH activity (OR: 0.63, 95% CI: 0.41-0.98) in coke oven workers. Moreover, by constructing various BEAS-2B cell models exposed to benzo[a]pyrene (BaP), we investigated that H19 binding to SAHH exaggerated DNMT1 expressions and activity. Suppression of H19 enhanced the interaction of SAHH and DNMT1 in BaP-treated cells, decreased eight-oxoguanine DNA glycosylase 1 (OGG1) methylation, reduced oxidative DNA damage and lessened S phase arrest. However, SAHH or DNMT1 single knockdown and SAHH/DNMT1 double knockdown showed the opposite trend. A H19/SAHH/DNMT1 axis was involved in OGG1 methylation, oxidative DNA damage and cell cycle arrest by carcinogen BaP.

Association of urinary polycyclic aromatic hydrocarbon metabolites with symptoms among autistic children: A case-control study in Tianjin, China.

Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous pollutants that are associated with altered neurodevelopment and various neurodevelopmental disorders. However, studies evaluating internal biomarkers of PAH exposure in reference to the severity of autism spectrum disorder (ASD) symptomology and autistic behaviors are scarce. Hence, we conducted a case-control study evaluating 12 urinary hydroxylated PAH metabolites (i.e., hydroxy-PAHs) in 101 children with autism and 101 neurotypical children, matching according to sex and age in a 1:1 ratio. In children with ASD, the severity of symptomology and autistic behaviors were assessed using the child autism rating scale (CARS) and the autism behavior checklist (ABC). We found that urinary levels of nine of the hydroxy-PAHs were statistically significantly higher in the ASD group, with the exception of 2-hydroxynaphthalene (2-OHNap) and 4-hydroxyphenanthrene (4-OHPhe). Moreover, urinary hydroxy-PAH levels were associated with ASD risk, with odds ratios ranging from 1.86 to 17.19. Exposures to 1-hydroxynaphthalene (1-OHNap, β=3.32), hydroxyphenanthrenes (1/2/3 + 9-OHPhes, β=3.41-5.12), 1-hydroxypyrene (1-OH-Pyr; β=3.91), 2-hydroxybenzofuran (2-OHDBF; β=3.93), and ∑OH-PAHs (β=4.67) were positively associated with CARS scores after adjusting for covariates (all p &lt; 0.05). When applying the ABC scale, 1-OHPyr levels were positively associated with ABC total scores (β=18.54), with the strongest associations evidenced in regard to the social relatedness (β=6.51) and language domains (β=6.51) (all p &lt; 0.05). Bayesian kernel machine regression (BKMR) showed consistent positive exposure responses for 1-OHNap, 1-OHPhe, and 3 + 9-OHPhe levels in regard to CARS scores, and for 1-OHPyr levels in regard to ABC total scores. Our findings suggest that children with ASD may have higher urinary levels of hydroxy-PAHs, and that these biomarker levels are associated with an increased odds of ASD, an increased severity of autism symptomology, and increased autistic behaviors in children with autism. LAY SUMMARY: We conducted an epidemiologic study evaluating the associations of urinary hydroxy-PAH levels with autism spectrum disorder (ASD), autism symptomology, and autistic behaviors. We found that urinary hydroxy-PAHs were statistically significantly associated with ASD. We note strong statistically significant associations between 1-OHNap, 1-OHPhe, and 3 + 9-OHPhe levels and increased severity of autism symptomology, as well as a strong statistically significant association between 1-OHPyr levels and behavioral characteristics within the social and linguistic domains. This work, if confirmed, will contribute to the future development of diagnostics for children with mild autism, as well as to environmental measures to promote the health and wellbeing of children with autism spectrum disorders.

Assessment of the association of exposure to polycyclic aromatic hydrocarbons, oxidative stress, and inflammation: A cross-sectional study in Augsburg, Germany.

Exposure to polycyclic aromatic hydrocarbons (PAHs) has been linked to acute and chronic health effects through the suggested pathways of oxidative stress and inflammation. However, evidence is still limited. We aimed to investigate jointly the relationship of PAHs, oxidative stress, and inflammation. We measured 13 biomarkers of PAH exposure (n=6: hydroxylated polycyclic aromatic hydrocarbons, [OH-PAHs]), oxidative stress (n=6: malondialdehyde (MDA); 8-hydroxy-2'-deoxyguanosine (8-OHdG); and 4 representatives of the compound class of F2α-isoprostanes) in urine, and inflammation (n=1: high-sensitivity C-reactive protein, [hs-CRP]) in serum from 400 participants at the second follow-up (2013/2014) of the German KORA survey S4. Multiple linear regression models were applied to investigate the interplay between biomarkers. Concentrations of biomarkers varied according to sex, age, smoking status, season, and a history of obesity, diabetes, or chronic kidney disease. All OH-PAHs were significantly and positively associated with oxidative stress biomarkers. An interquartile range (IQR) increase in sum OH-PAHs was associated with a 13.3% (95% CI: 9.9%, 16.9%) increase in MDA, a 6.5% (95% CI: 3.5%, 9.6%) increase in 8-OHdG, and an 8.4% (95% CI: 6.6%, 11.3%) increase in sum F2α-isoprostanes. Associations were more pronounced between OH-PAHs and F2α-isoprostanes but also between OH-PAHs and 8-OHdG for participants with potential underlying systemic inflammation (hs-CRP ≥ 3mg/L). We observed no association between OH-PAHs and hs-CRP levels. While 8-OHdG was significantly positively associated with hs-CRP (13.7% [95% CI: 2.2%, 26.5%] per IQR increase in 8-OHdG), F2α-isoprostanes and MDA indicated only a positive or null association, respectively. The results of this cross-sectional study suggest, at a population level, that exposure to PAHs is associated with oxidative stress even in a low exposure setting. Oxidative stress markers, but not PAHs, were associated with inflammation. Individual risk factors were important contributors to these processes and should be considered in future studies. Further longitudinal studies are necessary to investigate the causal chain of the associations.

A novel approach to predict the comprehensive EROD potency: Mechanism-based curve fitting of CYP1A1 activity by PAHs

Cytochrome P450 1A1 (CYP1A1) plays critical roles in polycyclic aromatic hydrocarbon (PAH) toxicity, including DNA adduction and ROS generation. Therefore, CYP1A1 activity quantified by the 7-ethoxyresorufin-O-deethylase (EROD) assay (named EROD potency) has been considered a typical biomarker of PAH exposure and toxicity. The EROD dose–response curve always presents a biphasic style, increasing at low concentrations and decreasing at high concentrations of PAHs, but relative effect potency (REP) commonly used in PAH risk assessment is only involved in the increasing phase. In this study, a full bell-shaped EROD curve fitting formula Eq. (1) was obtained by considering both CYP1A1 mRNA induction and enzyme inhibition to completely assess the EROD potency of PAHs. Correspondingly, in silico models of QSAR and docking methods successfully predicted the full EROD curves of PAHs, and the structure-activity relationship indicated that PAHs with heavy molecular weight and large diameter showed stronger EROD potency. Further EROD potency with predicted curve parameters (EC50,ind and area index) was confirmed by the reported REP (R2 = 0.697–0.977) and experimental data from human and mouse cells (R2 = 0.700–0.804). This study provides a novel curve fitting for the EROD dose–response relationship and a prediction model for PAH EROD potency.

Exposure assessment of polycyclic aromatic hydrocarbons in refined coal tar sealant applications.

Refined coal tar sealant (RCTS) emulsions are used to seal the surface of asphalt pavement. Nine of the 22 polycyclic aromatic hydrocarbons (PAHs) evaluated in this study are classified as known, probable, or possible human carcinogens. Exposure assessment research for RCTS workers has not been published previously. The overall objective of this study was to develop a representative occupational exposure assessment of PAH exposure for RCTS workers based on worksite surveys. The specific aims were to: 1) quantify full-shift airborne occupational exposures to PAHs among RCTS workers; 2) quantify workers' dermal exposures to PAHs; 3) quantify biomarkers of PAH exposure in workers' urine; 4) identify specific job titles associated with RCTS exposure; and 5) apply these results to a biological exposure index to assess risk of potential genotoxicity from occupational exposures. A total of twenty-one RCTS workers were recruited from three companies. Personal and area air samples were collected using a modification of NIOSH Method 5515. Dermal exposure was assessed by hand and neck wipes before and after shifts. Twenty-two PAHs were quantified via gas chromatography-mass spectrometry selected ion monitoring. Internal dose was estimated by quantifying select PAH metabolites in pre- and post-shift urine samples using on-line solid phase extraction-high performance liquid chromatography-tandem mass spectrometry. PAH levels in the worker breathing zones were highest for naphthalene, acenaphthene, and phenanthrene, with geometric means of 52.1, 11.4, and 9.8μg/m3, respectively. Hand wipe levels of phenanthrene, fluoranthene and pyrene were the highest among the 22 PAHs with geometric means of 7.9, 7.7, and 5.5μg/cm2, respectively. Urinary PAH biomarkers for naphthalene, fluorene, phenanthrene, and pyrene were detected in all workers and were higher for post-shift samples than those collected pre-shift. Urinary concentrations of the metabolite 1-hydroxypyrene were greater than the American Conference of Governmental Industrial Hygienists (ACGIH) Biological Exposure Index (BEI) for this metabolite in 89 percent of post-shift samples collected on the final day of the work week or field survey. Statistically significances were found between concentrations of fluorene, naphthalene, and phenanthrene in the breathing zone of workers and their corresponding urinary PAH biomarkers. Workers were placed in two work place exposure groups: applicators and non-applicators. Applicators had higher total PAH concentrations in personal breathing zone (PBZ) air samples than non-applicators and were more likely to have post-shift hand wipe concentrations significantly higher than pre-shift concentrations. Concentrations of post-shift urinary biomarkers were higher, albeit not significantly, for applicators than non-applicators. The exposure results from RCTS worker samples cannot be explained by proximal factors such as nearby restaurants or construction. Air and skin concentration levels were substantially higher for RCTS workers than previously published levels among asphalt workers for all PAHs. PAH profiles on skin wipes were more consistent with RCTS sealant product than air samples. Last day post-shift urinary concentrations of 1-hydroxypyrene greatly exceeded the ACGIH BEI benchmark of 2.5μg/L in 25 of 26 samples, which suggests occupational exposure and risk of genotoxicity. When pyrene and benzo[a]pyrene were both detected, concentration ratios from personal exposure samples were used to calculate the adjusted BEI. Concentrations of 1-hydroxypyrene exceeded the adjusted BEIs for air, hand wipes, and neck wipes in most cases. These results indicate the need to increase safety controls and exposure mitigation for RCTS workers.

Urinary polycyclic aromatic hydrocarbons and sex hormones in children and adolescents: Evidence from NHANES

BackgroundEvidences showed that polycyclic aromatic hydrocarbons (PAHs) do harm to human body. However, the association between PAHs and sex hormones in children and adolescents remains unclear. ObjectivesThe study aims to investigate the associations between PAHs and sex hormones in the general children and adolescent population. Methods967 participants aged 6–19 with complete data of PAHs exposure biomarkers, covariates and sex hormones [total testosterone (TT), estradiol (E2) and sex hormone binding globulin (SHBG)] were recruited from National Health and Nutrition Examination Survey (NHANES), 2013–2016. Free androgen index (FAI) was calculated with TT/SHBG. Multivariate linear regression models were performed in six subgroups (male children, male adolescents, male late adolescents, female children, female adolescents and female late adolescents) to estimate the associations between sex hormone alterations and PAHs exposure. ResultsIn male puberty adolescents, weighted multivariate linear regression indicated that negative trends for 2-Hydroxynaphthalene, 1-Hydroxyphenanthrene, 2&3-Hydroxyphenanthrene and E2 (2-Hydroxynaphthalene: β: −0.104, 95%CI: −0.180, −0.029, P < 0.01; 1-Hydroxyphenanthrene: β: −0.112, 95%CI: −0.206, −0.018, P = 0.019; 2&3-Hydroxyphenanthrene: β: −0.125, 95%CI: −0.232, −0.018, P = 0.022), while exposure to 2-Hydroxynaphthalene was related to TT reduction (β: −0.099, 95%CI: −0.177, −0.020, P = 0.014). Same pattern between 2&3-Hydroxyphenanthrene and E2 alteration (2&3-Hydroxyphenanthrene: β: −0.139, 95%CI: −0.236, −0.041, P < 0.01) was also observed in male late adolescents. In male children, we determined that 1-Hydroxyphenanthrene was negatively associated with SHBG (β: −0.121, 95%CI: −0.205, −0.037, P < 0.01), while the same patterns were observed in male puberty children. We did not observe any significant result in female subgroups. All these results above were determined to have q value < 0.05. ConclusionPAHs exposure was associated with the alterations of sex hormones in male adolescents and children. Considering the cross-sectional study design, further large-scale epidemiological study is necessary.

Seasonal variation of polycyclic aromatic hydrocarbon metabolites in bile of white perch Morone americana from two Chesapeake Bay tributaries.

Polycyclic aromatic hydrocarbon (PAH) accumulation in the bile is a reliable biomarker of recent exposure to environmental PAH and elevated concentrations have been identified as significant risk factors for hepatic disease in some fish species. Recent surveys (spring 2019) revealed a high incidence of hepatic lesions in white perch Morone americana from Chesapeake Bay, but this initial survey did not detect an association between PAH metabolites and lesions. Seasonal sampling of fish was extended through the winter 2020 to increase the metabolite and hepatic lesion database and better understand annual PAH exposures to white perch. Naphthalenes, phenanthrenes, and benzo[a]pyrenes (equivalents) were analyzed in bile specimens (n = 400) using high-performance liquid chromatography with fluorescence detection. Mean concentrations of metabolites were highest in fish collected from the urbanized Severn River in summer and were lowest in fish from the more rural Choptank River in winter. Variance in metabolite concentrations were primarily due to location and season. Seasonal fluctuations in water temperature, river discharge, or feeding status had little influence on the pattern of metabolite concentrations observed. The results suggest higher exposures of fish to environmental PAH in the more developed Severn River with significant increases during summer, which could correspond to a spike in seasonal recreational motor boat use or other human activities. A better understanding of the factors that contribute to variability in PAH metabolism and the enterohepatic biliary circulation in white perch will improve the usefulness of biliary metabolites as a biomarker of PAH exposure in Chesapeake Bay and elsewhere.

Telomere length mediates the association between polycyclic aromatic hydrocarbons exposure and abnormal glucose level among Chinese coke oven plant workers

IntroductionDiabetes is a chronic and complex disease determined by environmental and genetic factors. This study aimed to investigate the association between polycyclic aromatic hydrocarbons (PAHs) exposure and fasting blood glucose levels and telomere length among coke-oven plant workers, to explore potential role of telomere length (TL) in the association between PAHs exposure and abnormal glucose level. MethodsThe cross-sectional survey was conducted in 2017. The high-performance liquid chromatography mass spectrometry (HPLC-MS) was used to detect 11 urine biomarkers of PAHs exposure. TL was measured using the Real-time quantitative polymerase chain reaction (RT-qPCR) method. Logistic regression model, the modified Poisson regression models, and mediation analysis were used to evaluate the associations between PAHs exposure, TL, and abnormal glucose. ResultsThe results showed that the urinary 1-hydroxypyrene (1-PYR) was positively related to abnormal glucose in a dose-dependent manner (Ptrend = 0.007), the prevalence ratio of abnormal glucose was 8% (95% CI: 1.01–1.16) higher in 3rd tertile of urinary 1-PYR levels. Urinary 1-PYR in the 2nd tertile and 3rd tertile were associated with a 53% (OR = 0.47, 95% CI: 0.28–0.79) and 59% (OR = 0.41, 95% CI: 0.23–0.76) higher risk of shortening TL. And there was a negatively association between 1-PYR and TL in a dose-dependent manner (Ptrend = 0.045). We observed that the association between 1-PYR and abnormal glucose was more significantly positive among participants with median TL level (Ptrend = 0.006). In addition, mediation analysis showed the TL could explain 11.7% of the effect of abnormal glucose related to PAHs exposure. ConclusionsOur findings suggested the effect of abnormal glucose related to PAHs exposure was mediated by telomere length in coke oven plant workers.

Exposure to polycyclic aromatic hydrocarbons (PAHs) in people living in urban and rural areas as revealed by hair analysis.

Some polycyclic aromatic hydrocarbons (PAHs) are carcinogenic and mutagenic to humans. However, little is known about PAH exposure to people living in urban and suburban areas through comparative studies. Some studies have indicated that human hair can be used as a noninvasive biomarker of PAH exposure. Therefore, we collected hair samples from 66 volunteers from Nanjing and Ningbo, China, to detect PAH concentrations in this work. The highest levels in the hair samples were found in phenanthrene>anthracene>naphthalene among the parent PAHs. Sixteen parent PAHs showed higher concentrations in the samples from Nanjing than in the samples from Ningbo. Significantly higher levels of some PAHs were observed in male hair than in female hair in Nanjing, and in hair from smokers than in hair from non-smokers in both Nanjing and Ningbo. In addition, there was a significant effect of the age on the concentration of low-molecular-weight PAHs and ∑PAHs in human hair in both Nanjing and Ningbo. Studying the inter-chemical associations between these PAHs indicated similarities and differences between Nanjing and Ningbo.

Insights into biomonitoring of human exposure to polycyclic aromatic hydrocarbons with hair analysis: A case study in e-waste recycling area

In this study, 96 pairs of hair and urine samples were collected from e-waste (EW) dismantling workers of an industrial park, as well as residents living in surrounding areas. The concentrations of polycyclic aromatic hydrocarbons (PAHs) and hydroxylated PAH metabolites (OH-PAHs) were analyzed . The results show that concentrations of Σ15PAHs ranged from 6.24 to 692 ng/g dry weight (dw) and Σ12OH-PAHs from undetected to 187 ng/g dw in hair external (hair-Ex), and ranged from 31.7 to 738 ng/g dw and 21.6 to 1887 ng/g dw in hair internal (hair-In). There was no significant difference in exposure levels between EW dismantling workers and residents of the surrounding area. For the parent PAHs, the concentrations of Σ15PAHs of hair-In were comparable with those of hair-Ex for all populations except for the child residents. On the contrary, for the OH-PAHs, the concentrations of Σ12OH-PAHs of hair-In were 9–37 times higher than those of hair-Ex for populations. Moreover, the congener profiles of OH-PAHs of hair-In were different from those of hair-Ex, but similar to that of urine. Particularly, 3-OH-Bap, which is a carcinogenic metabolite, was only detected in the hair-In. These results indicate that OH-PAHs in hair-In, just like in urine, are mainly derived from endogenous metabolism and could be considered as reliable biomarkers for PAHs exposure. However, there was almost no significant correlations between hair-In and urine for OH-PAHs. This indicates that more attention should be paid to OH-PAHs when conducting PAHs exposure risk assessment using hair, which will help to obtain more reliable and comprehensive information on health risk assessments.

PAHs increase the production of extracellular vesicles both in vitro in endothelial cells and in vivo in urines from rats

Environmental contaminants, to which humans are widely exposed, cause or worsen several diseases, like cardiovascular diseases and cancers. Among these molecules, polycyclic aromatic hydrocarbons (PAHs) stand out since they are ubiquitous pollutants found in ambient air and diet. Because of their toxic effects, public Health agencies promote development of research studies aiming at increasing the knowledge about PAHs and the discovery of biomarkers of exposure and/or effects.Extracellular vesicles (EVs), including small extracellular vesicles (S-EVs or exosomes) and large extracellular vesicles (L-EVs or microvesicles), are delivery systems for multimolecular messages related to the nature and status of the originating cells. Because they are produced by all cells and detected within body fluids, EV releases could act as cell responses and thereby serve as biomarkers.To test whether EVs can serve as biomarkers of PAHs exposure, we evaluate the effects of these pollutants on EV production using an in vitro approach (human endothelial cell line, HMEC-1) and an in vivo approach (urine samples from PAHs-exposed rats). Our study indicates that, i) PAH exposure increases in vitro the EV production by endothelial cells and in vivo the release of EVs in urine, and that the stimulating effects of PAHs concern both S-EVs and L-EVs; ii) PAH exposure and more particularly exposure to B[a]P, can influence the composition of exosomes produced by endothelial cells; iii) the aryl hydrocarbon receptor, a cytosolic receptor associated to most deleterious effects of PAHs, would be involved in the PAH effects on the release of S-EVs, but not L-EVs.These results suggest that EVs may have utility for monitoring exposure to PAHs, and more particularly to B[a]P, considered as reference PAH, and to detect the related early cellular response prior to end-organ damages.

Co-exposure to polycyclic aromatic hydrocarbons and metals, four common polymorphisms in microRNA genes, and their gene-environment interactions: Influences on oxidative damage levels in Chinese coke oven workers

BackgroundHuman are often simultaneously exposed to polycyclic aromatic hydrocarbons (PAHs) and metals, yet relatively little is known regarding their co-exposure effects on oxidative damage. Genetic factors and the gene-environment interactions can also determine the severity of oxidative damage. Four polymorphisms in microRNA (miRNA) genes (rs11614913, rs2292832, rs2910164, and rs3746444) have been well-studied to be associated with oxidative damage-related diseases. ObjectiveTo investigate the influences of PAH-metal co-exposure, four polymorphisms, and their interactions on oxidative damage levels. MethodsWe conducted a cross-sectional study in 1385 coke oven workers. We quantified exposure levels of PAHs and metals by urinary monohydroxy-PAHs, plasma benzo[a]pyrene-7,8-diol-9,10-epoxide-albumin adducts, and urinary metals, respectively, and measured oxidative damage levels by 8-iso-prostaglandin-F2α and 8-hydroxydeoxyguanosine. We also genotyped four polymorphisms. ResultsIn multiple-pollutant models, 8-iso-prostaglandin-F2α and 8-hydroxydeoxyguanosine were associated with multiple PAH exposure biomarkers, as well as with multiple metals (ptrend < 0.05). Metabolites of phenanthrene and pyrene interacted synergistically with lead and zinc to influence 8-iso-prostaglandin-F2α (βinteraction > 7.75%, false discovery rate-adjusted pinteraction ≤ 2.25 × 10−5). Significantly higher 8-hydroxydeoxyguanosine was observed in carriers of rs11614913 CC variant homozygote than TC carriers (p = 0.037). Associations of the number of rs11614913 C allele with increased 8-iso-prostaglandin-F2α and 8-hydroxydeoxyguanosine were significant (βstd > 0, ptrend < 0.05) and more pronounced in workers with lower metals [p for modifying effect (pME) < 0.040]. Positive associations of some PAHs and metals with 8-iso-prostaglandin-F2α and 8-hydroxydeoxyguanosine were weaker in carriers of rs11614913 CC genotype or C allele (pME < 0.05). ConclusionPAH-metal co-exposure, rs11614913, and their interactions may affect oxidative damage levels in Chinese population in a complex manner that are worthy of further investigation.

CYP1A1 methylation mediates the effect of smoking and occupational polycyclic aromatic hydrocarbons co-exposure on oxidative DNA damage among Chinese coke-oven workers

BackgroundMultiple factors, including co-exposure between lifestyle and environmental risks, are important in susceptibility to oxidative DNA damage. However, the underlying mechanism is not fully understood. This study was undertaken to evaluate whether Cytochrome P4501A1 (CYP1A1) methylation can mediate the co-exposure effect between smoking and occupational polycyclic aromatic hydrocarbons (PAH) in development of oxidative DNA damage.MethodsWe explored the associations between smoking and occupational PAH co-exposure effect, CYP1A1 methylation and oxidative DNA damage among 500 workers from a coke-oven plant in China. Urine biomarkers of PAH exposure (1-hydroxypyrene, 1-OHP; 2-hydroxynaphthalene, 2-NAP; 2-hydroxyfluorene, 2-FLU; and 9-hydroxyphenanthren, 9-PHE) and a marker of oxidative DNA damage (8-hydroxy- 2′- deoxyguanosine, 8-OHdG) were measured by high performance liquid chromatography. CYP1A1 methylation was measured by pyrosequencing. Finally, mediation analysis was performed to investigate whether CYP1A1 methylation mediated smoking and occupational PAH co-exposure effect on oxidative DNA damage.ResultsWe observed significant associations of smoking and 1-OHP co-exposure with CYP1A1 hypomethylation (OR: 1.87, 95% CI: 1.01–3.47) and high 8-OHdG (OR: 2.13, 95% CI: 1.14–3.97). There was a significant relationship between CYP1A1 hypomethylation and high 8-OHdG (1st vs. 3rd tertile = 1.58, 95% CI: 1.01–2.47, P for trend = 0.046). In addition, mediation analysis suggested CYP1A1 hypomethylation could explain 13.6% of effect of high 8-OHdG related to smoking and 1-OHP co-exposure.ConclusionsOur findings suggested that the co-exposure effect of smoking and occupational PAH could increase the risk of oxidative DNA damage by a mechanism partly involving CYP1A1 hypomethylation.

Glycosylation of polycyclic aromatic hydrocarbons by UDP‐glycosyltransferase 3A2 (UGT3A2) and aerodigestive tract tissues

Smoking is a primary risk factor for the development of lung and tobacco‐related cancers. There are over 70 carcinogens in tobacco smoke, and they belong to multiple chemical classes including polycyclic aromatic hydrocarbons (PAHs). The UDP‐glycosyltransferase (UGT) family of enzymes play a key role in the detoxification of several major tobacco carcinogens by glucuronidation, using UDP‐glucuronic acid as cosubstrate. While the UGT 1As, 2As, and 2Bs are well known to detoxify simple and complex PAHs, the UGT3A subfamily has been understudied in the detoxification of PAHs. UGT3A2 uses UDP‐glucose and UDP‐xylose as cosubstrates and is active against 1‐hydroxypyrene, a biomarker for PAH exposure. Our previous research has shown that UGT3A2 is expressed in the aerodigestive tract and is active against simple hydroxylated PAHs. The purpose of the present study was to determine the kinetic parameters of UGT3A2 against complex PAHs and determine glycosylation in aerodigestive tract tissues using UDP‐glucose and UDP‐xylose. Microsomes prepared from UGT3A2 overexpressing HEK293 cells exhibited glycosylation activity against complex PAHs including benzo[a]pyrene (B[a]P)‐7,8‐diol, B[a]P‐9,10‐diol, DB[a, l]P‐11,12‐diol, and 5‐methylchrysene‐1,2‐diol, with Km's ranging from 96 to 1250 μM using UDP‐glucose. The Km's were significantly lower when using UDP‐xylose, with Km's ranging from 120 to 168 μM for the same substrates. The Vmax/Km ratio of UDP‐xylose/UDP‐glucose ranged from 0.71 to 4.0. To determine the physiological significance and relevance of UDP‐xylose‐ and UDP‐glucose‐dependent glycosylation, activity assays were performed in tissues where UGT3A2 is expressed using 1‐hydroxypyrene as substrate. Using UDP‐glucose as the cosubstrate, glycosylation rates of 3.5, 5.2, and 13 pmol·min−1·mg−1 were observed for liver, intestine and kidney microsomes, respectively. The rates were higher using UDP‐xylose, with rates of 22, 9.3, and 20 pmol·min−1·mg−1 for liver, intestine and kidney, respectively. The glycosylation rate ratio for UDP‐xylose/UDP‐glucose ranged from 1.6 to 6.3 in the three tissues, with liver exhibiting the highest ratio. In addition, detectable glycosylation activity was observed in various aerodigestive tract tissues including esophagus, tonsil, bronchus, floor of mouth, tongue, trachea, and larynx, with tonsil exhibiting the highest relative activity with both UDP‐sugars. Incubations with UDP‐xylose resulted in higher levels of glycosylation activity than that observed with UDP‐glucose in esophagus, tonsil, floor of mouth, and larynx. These data suggest that UGT3A2 is playing an important role in the detoxification of PAHs in tobacco target tissues, with UDP‐xylose being the preferred cosubstrate in most tissues.Support or Funding InformationThis study is supported by the National Institute of Environmental Health Sciences (NIEHS) of the National Institutes of Health to P Lazarus (Grant R01‐ES025460), a NIEHS Research Supplement to Promote Diversity in Health‐Related Research to AG Vergara (Grant R01‐ES025460‐02S1), and a grant from the Health Sciences and Services Authority of Spokane, WA (Grant WSU002292).This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

The impact on T-regulatory cell related immune responses in rural women exposed to polycyclic aromatic hydrocarbons (PAHs) in household air pollution in Gansu, China: A pilot investigation

Previous studies found associations between impairments of immune functions and exposure to polycyclic aromatic hydrocarbons (PAHs) in ambient air pollution in the U. S. and China. However, the results remain inconclusive due to the limitations of these studies. In this study, we aimed to examine the direction and magnitude of immune changes related to PAH exposure from household air pollution among rural women living in Gansu, China. Healthy village women (n = 34) were recruited and enrolled in the study. Questionnaires were administered. Blood and urine samples were collected and analyzed during non-heating (September 2017, “summer”) and heating (January 2018, “winter”) seasons. Urinary 1-hydroxypyrene (1-OHP) was quantified as the biomarker of PAH exposure. To evaluate Treg cell related immune functions, we examined immunoglobulin E (IgE), percent of T-regulatory (Treg) cells, and gene expression of following: forkhead box transcription factor 3 (Foxp3), transforming growth factor-β (TGF-β), interleukin 10 (IL-10), and interleukin 35 (IL-35), composed of interleukin-12 alpha (IL-12α) and Epstein-Barr-virus-induced gene 3 (EBi3). Urinary 8-hydroxy-2-deoxyguanosine (8-OHdG) was measured to evaluate oxidative DNA damage. The results showed that the concentration of 1-OHP increased from 0.90 to 17.4 μmol mol-Cr −1 from summer to winter (p < 0.001). Meanwhile, average percent of Treg cells decreased from 5.01% to 1.15% (p < 0.001); IgE and mRNA expressions of Foxp3, TGF-β, IL-10, IL-12α and EBi3 all significantly decreased (p < 0.001); Urinary 8-OHdG increased from 12.7 to 30.3 ng mg-Cr −1 (p < 0.001). The changes in 8-OHdG, Foxp3 and TGF-β were significantly associated with the increase of 1-OHP. The results suggested that we observed a substantial increase of PAH exposure in winter, which was significantly associated with the repression on Treg cell function and oxidative DNA damage. Exposure to PAHs in household air pollution possibly induced immune impairments among rural women in northwest China.

OGG1 methylation mediated the effects of cell cycle and oxidative DNA damage related to PAHs exposure in Chinese coke oven workers

Previous publications have indicated that polycyclic aromatic hydrocarbons (PAHs) exposures are associated with increased DNA damage and abnormal cell cycle arrest; however, the details of mechanisms remain largely unknown. This study aimed to quantify the associations of 8-oxoguanine DNA glycosylase (OGG1) methylation with urinary PAHs metabolites, DNA damage and cell cycle arrest, and further to assess the role of OGG1 methylation in mediating the association of urinary PAHs metabolites with DNA damage and cell cycle arrest. Urinary biomarkers of PAHs exposure and a marker of oxidative DNA damage (8-hydroxy-2′-deoxyguanosin, 8-OHdG) were measured by high performance liquid chromatography. Cell cycle of lymphocyte was analysed with flow cytometry and OGG1 methylation in venous blood was measured by pyrosequencing. After adjusting for covariates, urinary 1-OHP levels were positively associated with lymphocyte S phase arrest and oxidative DNA damage, while were negatively associated with G0/G1 phase arrest. OGG1 methylation was not only positively correlated with urinary 1-OHP in a dose-responsive manner (P trend = 0.008) but was also associated with G0/G1 phase arrest (OR: 0.63, 95% CI: 0.41–0.97), S phase arrest (OR: 1.55, 95% CI: 1.01–2.40) and oxidative DNA damage (OR: 1.71, 95% CI: 1.02–2.86). Mediation analysis estimated that OGG1 methylation mediated about 20% of associations between urinary 1-OHP levels and cell cycle arrest and oxidative DNA damage, respectively (all P < 0.05). Our findings suggested that urinary 1-OHP concentrations were associated with cell cycle arrest and oxidative DNA damage by a mechanism partly involving OGG1 methylation.

Mediation effect of AhR expression between polycyclic aromatic hydrocarbons exposure and oxidative DNA damage among Chinese occupational workers

Polycyclic aromatic hydrocarbons (PAH) are well-known to be carcinogenic and the mechanisms that it contributes to oxidative DNA damage and aryl hydrocarbon receptor (AhR)-dependent induction are also well understood. However, little is known about the associations between PAH exposure, AhR expression, and oxidative DNA damage. We investigated their associations of AhR expression and oxidative DNA damage related to PAH exposure among 310 workers from a coke-oven plant in China. Urine biomarkers of PAH exposure (2-hydroxynaphthalene, 2-NAP; 2-hydroxyfluorene, 2-FLU; 9-hydroxyphenanthren, 9-PHE; and 1-hydroxypyrene, 1-OHP) and a marker of oxidative damage (8-hydroxy- 2′- deoxyguanosine, 8-OHdG) were measured by high performance liquid chromatography. AhR expression in venous blood was measured by reverse transcription -polymerase chain reaction. The results showed that increasing levels of urinary 1-OHP was positively associated with high 8-OHdG (OR (95% CI) was 4.01 (1.41–11.45) for 4th quartile, compared with 1st quartile, P for trend = 0.013). The similar associations were also found between urinary 1-OHP and high-AhR expressions (4th vs. 1st quartile = 3.50, 95% CI: 1.24–9.87, P for trend = 0.029). A significant association between AhR expression and high 8-OHdG was also found (4th vs. 1st quartile = 2.44, 95% CI: 1.05–5.70, P for trend = 0.027). In addition, mediation analysis showed the AhR expression could explain 35.9% of the association of oxidative DNA damage related to PAH exposure. Our findings implicated that the association between PAH exposure and oxidative DNA damage may be mediated by AhR expression among Chinese occupational workers.