Urinary Polycyclic Aromatic Hydrocarbons Research Articles

The interaction effects of polycyclic aromatic hydrocarbons exposure and TERT- CLPTM1L variants on longitudinal telomere length shortening: A prospective cohort study

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 (Pinteraction = 0.012 and 0.035, respectively) and TL ratio (Pinteraction = 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.

High-Throughput Analysis of Selected Urinary Hydroxy Polycyclic Aromatic Hydrocarbons by an Innovative Automated Solid-Phase Microextraction.

High-throughput screening of samples is the strategy of choice to detect occupational exposure biomarkers, yet it requires a user-friendly apparatus that gives relatively prompt results while ensuring high degrees of selectivity, precision, accuracy and automation, particularly in the preparation process. Miniaturization has attracted much attention in analytical chemistry and has driven solvent and sample savings as easier automation, the latter thanks to the introduction on the market of the three axis autosampler. In light of the above, this contribution describes a novel user-friendly solid-phase microextraction (SPME) off- and on-line platform coupled with gas chromatography and triple quadrupole-mass spectrometry to determine urinary metabolites of polycyclic aromatic hydrocarbons 1- and 2-hydroxy-naphthalene, 9-hydroxy-phenanthrene, 1-hydroxy-pyrene, 3- and 9-hydroxy-benzoantracene, and 3-hydroxy-benzo[a]pyrene. In this new procedure, chromatography’s sensitivity is combined with the user-friendliness of N-tert-butyldimethylsilyl-N-methyltrifluoroacetamide on-fiber SPME derivatization using direct immersion sampling; moreover, specific isotope-labelled internal standards provide quantitative accuracy. The detection limits for the seven OH-PAHs ranged from 0.25 to 4.52 ng/L. Intra-(from 2.5 to 3.0%) and inter-session (from 2.4 to 3.9%) repeatability was also evaluated. This method serves to identify suitable risk-control strategies for occupational hygiene conservation programs.

Urinary polycyclic aromatic hydrocarbons and allergic sensitization in a nationwide study of children and adults in the United States

Urinary polycyclic aromatic hydrocarbons and allergic sensitization in a nationwide study of children and adults in the United States

Exposure to polycyclic aromatic hydrocarbons, vitamin D, and lung function in children with asthma.

It is unclear whether exposure to polycyclic aromatic hydrocarbons (PAH) affects lung function in children with asthma. Whether vitamin D insufficiency enhances any detrimental effects of PAH on lung function in asthmatic children is also unknown. Cross-sectional study of 1,821 children (6-17 years) who participated in the 2007-2012 National Health and Nutrition Examination Survey. Multivariable linear regression was used to analyze the relation between molar mass of urinary PAH metabolites (sum of all PAH (ΣmolPAH), sum of PAH with 2 benzene rings (Σmol2-PAH), or sum of PAH with 3 or 4 benzene rings (Σmol3,4-PAH)) and lung function or exhaled fraction of nitric oxide (FeNO) in children with and without asthma. In this multivariable analysis, we tested whether vitamin D insufficiency (a serum 25(OH)D level <30 ng/mL) interacts with PAH exposure on lung function in children with asthma. Children in the highest quartiles of urinary Σmol3,4-PAH had 2.3 times increased odds of asthma than those in the lowest quartile of Σmol3,4-PAH. Urinary PAH were not associated with lung function in children with or without asthma. Given a significant interaction between vitamin D insufficiency and PAH metabolites on lung function in asthmatic children, we stratified the analysis by vitamin D status. In this analysis, urinary PAH metabolites were significantly associated with 2.7-3.9% reduced %predicted FEV1 and %predicted FEV1/FVC in children with asthma and vitamin D insufficiency, but not in those with asthma and vitamin D sufficiency. Vitamin D insufficiency and PAH exposure may have synergistic detrimental effects on lung function in asthmatic children.

ETS Exposure and PAH Body Burden in Nonsmoking Italian Adults.

Active smoking is associated with increased body burden of polycyclic aromatic hydrocarbons (PAHs); the aim of this study was to assess whether environmental tobacco smoking (ETS) increases the internal dose of PAHs. In 344 nonsmoking Italian adults, out of 497 individuals selected as representative of the population of the town of Modena, ETS exposure was evaluated by a self-administered questionnaire and by the measurement of urinary cotinine (COT-U). PAH exposure was assessed by the measurement of urinary 1-hydroxypyrene (1-OHPYR) and of ten urinary PAHs. In all subjects, median (5th–95th percentile) COT-U was 0.47 (<0.1–3.91) µg/L. While 58 subjects reported to be ETS exposed (ETSQUEST), 38 individuals were identified as ETS exposed on the basis of a COT-U value of 1.78 (90% confidence interval 1.75–1.80) µg/L, previously derived as an upper reference value in not ETS exposed Italian adults (ETSCOT). Median COT-U levels were 1.38 (<0.1–9.06) and 3.63 (1.80–17.39) µg/L in ETSQUEST and in ETSCOT subjects, respectively. Significant correlations between COT-U and 1-OHPYR, and urinary anthracene, fluoranthene, pyrene, and chrysene were found among all subjects. Significantly higher levels of 1-OHPYR, and urinary fluorene, anthracene, and pyrene were found in ETSCOT individuals. The results of multiple linear regression analyses, taking into consideration diet and other sources of PAHs exposures such as the residence area/characteristics and traffic, confirmed that 1-OHPYR and urinary fluorene were affected by ETS exposure, even if ETS played a minor role.

Characteristics and potential health risk of rural Tibetans' exposure to polycyclic aromatic hydrocarbons during summer period

Biomass fuels remain main energy sources in many remote rural regions, but potential health hazards from exposure to biomass combustion fumes have not been adequately assessed. Combustion of biomass fuels generates abundant polycyclic aromatic hydrocarbons (PAHs); hence residential exposure to PAHs can be used to evaluate the potential health risk to remote rural populations. The present study selected rural Tibetans to address the above-mentioned issue. Samples of indoor air and dust, human urine and local foods (Tsampa flour and buttered tea) were collected from five rural households in Langkazi County, an agricultural and pasturing region in Tibet of China in the summer season, which represented the best-case scenario as no heating was required. Residential exposure to PAHs by adults amounted to benzo[a]pyrene equivalent (BaPeq) dosages of 110–760, 1.2–50 and 0.5–23 ng d−1 for ingestion, inhalation and dermal contact, respectively. Daily intakes of naphthalene, fluorene, phenanthrene and pyrene estimated from urinary monohydroxy PAH metabolites and from diet and inhalation exposure to PAHs were comparable (3.9, 1.9, 12 and 3.3 μg d−1 versus 9.5, 2.5, 5.1 and 1.1 μg d−1), indicating the utility of external exposure in assessing daily intake of PAHs. The median incremental lifetime cancer risk was 32 × 10−6 (95% confidence interval: 0.7–73 × 10−6) for ingestion and 2.4 × 10−6 (95% confidence interval: 0.02–12 × 10−6) for inhalation and dermal contact combined, indicating moderate to slight potential cancer risk. Diet is the dominant source of health hazards for rural Tibetans, but cooking fumes also present a meaningful concern. The present study demonstrates that the pristine lifestyles of remote rural residents may be of global health concern, and merit further investigations.

Environmental and lifestyle factors affecting exposure to polycyclic aromatic hydrocarbons in the general population in a Middle Eastern area

The aim of this study was to investigate environmental and lifestyle factors affecting exposure to PAHs in the general population in a large city of the Middle East (Tehran) by measuring urinary monohydroxy polycyclic aromatic hydrocarbons (OH-PAHs) and establishing relationships between PAHs exposure and related factors. Urine samples were collected from 222 randomly chosen subjects who were living in the urban area of Tehran, Iran. Subjects were required to complete a detailed questionnaire aimed to document their personal and sociodemographic information, activities, cooking-related appliances, smoking history/exposure, and consumed foodstuff. Identification and quantification of six OH-PAHs was carried out using a gas chromatography with mass spectrometry (GC-MS). The geometric means for 1-OHP, 1-NAP, 2-NAP, 2-FLU, 9-FLU, and 9-PHE for whole population study were 310, 1220, 3070, 530, 330, and 130 ng/g creatinine, respectively. The two naphthalene metabolites contributed on average 77% of the total concentration of six measured OH-PAHs, followed by the 2-FLU, 1-OHP, 9-FLU, and 9-PHE. The most important predictors of urinary PAHs were consumption of grilled/barbecued foods, smoking, and exposure to environmental tobacco smoking. Water pipe smoking was linked to urinary OH-PAH metabolite in a dose-response function. Residential traffic was also related with OH-PAH metabolite concentrations. Other factors including gender, age, exposure to common house insecticides, open burning, and candle burning were found to be statistically associated with the urinary levels of some OH-PAHs. High exposure to PAHs among general population in Middle Eastern large cities and its associated health implications calls for public health measures to reduce PAHs exposure.

Urinary polycyclic aromatic hydrocarbon metabolites and adult asthma: a case-control study

Polycyclic aromatic hydrocarbons (PAHs) exposure was reported to be associated with childhood asthma. However, the quantitative relationship between PAHs exposure and adult asthma and possible inflammatory pathways are less clear. We aimed to investigate potential associations between urinary PAHs metabolites and adult asthma. We enrolled 507 adult asthma cases and 536 matched controls. The concentrations of 12 urinary PAHs metabolites and plasma cytokines of interleukin (IL)-9 and eotaxin were measured. Potential associations between urinary PAHs metabolites and adult asthma were analyzed by logistic regression. The relationships between urinary PAHs metabolites and plasma cytokines were determined by generalized linear regression. After adjusted for covariates, each 1-unit-increase in natural log-transformed concentrations of 2-hydroxyfluorene (2-OHFLU), 4- hydroxyphenanthrene (4-OHPHE), 1-OHPHE, 2-OHPHE, 1-Hydroxypyrene (1-OHPYR) and ∑OH-PAHs were significantly associated with elevated risk of adult asthma with odds ratios of 2.04, 2.38, 2.04, 1.26, 2.35 and 1.34, respectively. And the associations were more pronounced in the subjects who were female, younger than 45 years, smoker and had history of occupational dust exposure. No associations were observed between urinary PAHs metabolites levels and expressions of IL-9 and eotaxin. Our results demonstrated that elevated urinary PAHs metabolites levels were associated with increased risk of asthma in adults.

Associations of urinary polycyclic aromatic hydrocarbons with bone mass density and osteoporosis in U.S. adults, NHANES 2005–2010

Polycyclic aromatic hydrocarbons (PAHs) are environmental endocrine disruptors, which may modify the bone mineralization. However, epidemiological evidences on this issue were scant. We aimed to investigate the associations of PAHs with bone mass density (BMD) and osteoporosis based on a nationally-representative sample from general U.S. population. Data utilized were extracted from the 2005–2010 National Health and Nutrition Examination Survey (NHANES). Nine urinary PAHs (U-PAHs) metabolites were measured as exposure biomarkers. Associations of specific U-PAHs with BMD and osteoporosis were estimated by multivariable adjusted linear regression models and logistic regression models, respectively. Compared with women at the first tertiles, those at the third tertiles of 1-Hydroxynapthalene, 2-Hydroxyfluorene, 3-Hydroxyphenanthrene, 2-Hydroxyphenanthrene and 9-Hydroxyfluorene had significantly decreased BMD levels [coefficient (β) = −0.023 to −0.014, p < 0.05] or increased likelihoods of osteoporosis [odds ratios (ORs) = 1.86 to 3.36, p < 0.05] at different bone sites. Whereas, elevated BMD levels (β = 0.021, p < 0.05) at trochanter and decreased likelihoods of osteoporosis (OR = 0.33, p < 0.05) at intertrochanter were observed among women at the second tertiles of 1-Hydroxypyrene and 2-Hydroxynapthalene, respectively. Similar results were found for all the population, i.e., combination of men and women. Most of the significant associations disappeared among adult men only. Furthermore, Associations between U-PAHs and BMD were stronger for postmenopausal women when compared with premenopausal group. In conclusion, associations of U-PAHs with BMD and osteoporosis varied by specific U-PAHs and bone sites, as well as menopausal status and genders in U.S. adults.

DNA methylation of the cancer-related genes F2RL3 and AHRR is associated with occupational exposure to polycyclic aromatic hydrocarbons.

Some polycyclic aromatic hydrocarbons (PAH) are known carcinogens and workplace PAH exposure may increase the risk of cancer. Monitoring early cancer-related changes can indicate whether the exposure is carcinogenic. Here, we enrolled 151 chimney sweeps, 152 controls and 19 creosote-exposed male workers from Sweden. We measured urinary PAH metabolites using LC/MS/MS, the cancer-related markers telomere length (TL) and mitochondrial DNA copy number (mtDNAcn) using qPCR, and DNA methylation of lung cancer-related genes F2RL3 and AHRR using pyrosequencing. The median 1-hydroxypyrene (PAH metabolite) concentrations were highest in creosote-exposed workers (8.0 μg/g creatinine) followed by chimney sweeps (0.34 μg/g creatinine) and controls (0.05 μg/g creatinine). TL and mtDNAcn did not differ between study groups. Chimney sweeps and creosote-exposed workers had significantly lower methylation of AHRR CpG site cg05575921 (88.1 and 84.9%, respectively) than controls (90%). Creosote-exposed workers (73.3%), but not chimney sweeps (76.6%) had lower methylation of F2RL3 cg03636183 than controls (76.7%). Linear regression analyses showed that chimney sweeps had lower AHRR cg05575921 methylation (B = -2.04; P < 0.057, adjusted for smoking and age) and lower average AHRR methylation (B = -2.05; P < 0.035), and non-smoking chimney sweeps had lower average F2RL3 methylation (B = -0.81; P < 0.042, adjusted for age) compared with controls. These cancer-related markers were not associated with urinary concentrations of PAH metabolites. In conclusion, although we found no associations with PAH metabolites in urine (short-term exposure), our results suggest dose-response relationship between PAH exposure and DNA hypomethylation of lung cancer-related loci. These findings indicate that further protective measures should be taken to reduce PAH exposure.

Relationship between residence characteristics and polycyclic aromatic hydrocarbon exposure in housewives: second Korean National Environmental Health Survey (2012\u20132014)

BackgroundPolycyclic aromatic hydrocarbons (PAHs) produced by incomplete combustion have negative effects on human health due to their carcinogenicity and teratogenicity. Indoor sources of PAHs include tobacco smoke, heating sources, and cooking. This study evaluated the relationship between human PAH exposure and residence characteristics.MethodThis study was based on the second Korean National Environmental Health Survey (2012–2014). Non-smoking housewives were included in the analyses (n = 1269). The concentrations of urinary PAH metabolites (2-naphthol, 2-hydroxyfluorene, 1-hydroxyphenanthrene, and 1-hydroxypyrene) were adjusted by urine creatinine level. The geometric mean concentrations of urinary PAH metabolites by residential factors were examined. Logistic regression models were used to evaluate associations between residential variables and PAH exposures.ResultsThe adjusted geometric mean concentrations of urinary 2-hydroxyfluorene and 1-hydroxyphenanthrene were significantly higher in the group residing within 100 m of a major road (p < 0.05) than in those residing > 100 m from a major road. In logistic regression analyses, the odds ratio (OR) for exceeding the third quartile of urinary 1-hydroxypyrene concentration was significantly higher in the group using coal or wood fuel for residential heating than in the group using gas (OR = 2.745, 95% confidence interval [CI] = 1.295–5.819). The detached house group had a significantly higher OR for 1-hydroxyphenanthrene compared with the apartment group (OR = 1.515, 95% CI = 1.023–2.243).ConclusionOur study shows the evidence of associations between some urinary PAH metabolite levels (1-hydroxyphenanthrene and 1-hydroxypyrene) and residence characteristics. Additional studies are needed to clarify these associations.

Urinary polycyclic aromatic hydrocarbon metabolites among 3-year-old children from Krakow, Poland

Polycyclic aromatic hydrocarbons (PAHs) are widespread in the environment and can adversely affect human health. The aim of the present study is to describe the level of PAHs exposure in children living in Kraków, one of the most polluted cities in Poland, and to determine the relationship of urinary biomarkers with environmental PAHsexposure.Urinary monohydroxy metabolites (OH-PAHs) of 20 PAHs were assessed in 218 three-year old children, of which only 10 were present in nearly all the samples: monohydroxy metabolites of naphthalene, fluorene, phenantrene and pyrene. Of the metabolites analyzed, hydroxynaphthalenes were predominant and constituted almost 73% of total excreted OH-PAHs, while 1-OH-PYRene was the least abundant (2.3% of total OH-PAHs). All measured urinary OH-PAHs were statistically significantly correlated with each other (R = 0.165–0.880) but the highest correlation coefficients with other individual OH-PAHs and with total OH-PAHs were observed for 2-OH-FLUOR.Children exposed at home to environmental tobacco smoke (ETS) had higher concentrations of fluorene and pyrene urinary metabolites compared to those without ETS exposure; and those exposed to gas-based appliances used for cooking or heating water had higher levels of fluorene and phenanthrene metabolites than children not exposed. The use of coal, wood or oil for heating was associated with elevated levels of 1-OH-PYRene. Urinary PAHs metabolites only modestly reflect high molecular weight carcinogenic PAHs exposures such as those monitored in air in the present study. None of the measured PAHs metabolites was correlated with airborne PM2.5 and only two were slightly correlated with measured higher molecular mass airborne PAHs.The average concentrations of these specific metabolites in Polish children were much higher than observed in other pediatric populations living in developed countries. Our findings suggest that to capture various sources of PAHs, in addition to 1-OH-PYRene, biomonitoring of PAHs exposure should include 2-OH-NAP and 2-OH-FLUOR.

Urinary Concentrations of Polycyclic Aromatic Hydrocarbon Metabolites in Maté Drinkers in Rio Grande do Sul, Brazil.

Background: Consumption of maté, an infusion of the herb Ilex paraguariensis (yerba maté), is associated with increased risk of esophageal squamous cell carcinoma (ESCC), but the carcinogenic mechanism is unclear. Commercial brands of yerba maté contain high levels of carcinogenic polycyclic aromatic hydrocarbons (PAHs), which are acquired during the traditional drying process. The purpose of this study was to characterize exposure to PAHs in maté drinkers over a wide range of maté consumption.Methods: We recruited 244 adults who answered a questionnaire and collected a fasting spot urine specimen. We quantified urinary concentrations of seven PAH metabolites and assessed associations between self-reported recent maté consumption and urinary PAH metabolites by multivariate regression.Results: Recent maté consumption showed a significant dose-response association with 6 of 7 PAH metabolites in unadjusted models (Ptrend < 0.05). After adjustment for creatinine and potential confounders, concentrations of 2-naphthol, 1-hydroxyphenanthrene, and the sum of 2- and 3-hydroxyphenanthrene remained significantly associated with recent maté intake. The sum of the urinary concentrations of the phenanthrene metabolites was similar or higher among maté drinkers who did not smoke than among smokers who did not drink matéConclusions: Urinary concentrations of PAH metabolites were significantly associated with self-reported amounts of recent maté intake, and drinking maté increased urinary concentrations of some PAH metabolites as much as smoking cigarettes.Impact: Drinking maté is a source of exposure to potentially carcinogenic PAHs, consistent with the hypothesis that the PAH content of maté may contribute to the increased risk of ESCC in maté drinkers. Cancer Epidemiol Biomarkers Prev; 27(3); 331-7. ©2017 AACR.

Detection of monohydroxylated polycyclic aromatic hydrocarbons in urine and particulate matter using LC separations coupled with integrated SPE and fluorescence detection or coupled with high-resolution time-of-flight mass spectrometry.

A high-performance liquid chromatographic (HPLC) method with integrated solid-phase extraction for the determination of 1-hydroxypyrene and 1-, 2-, 3-, 4- and 9-hydroxyphenanthrene in urine was developed and validated. After enzymatic treatment and centrifugation of 500 μL urine, 100 μL of the sample was directly injected into the HPLC system. Integrated solid-phase extraction was performed on a selective, copper phthalocyanine modified packing material. Subsequent chromatographic separation was achieved on a pentafluorophenyl core-shell column using a methanol gradient. For quantification, time-programmed fluorescence detection was used. Matrix-dependent recoveries were between 94.8 and 102.4%, repeatability and reproducibility ranged from 2.2 to 17.9% and detection limits lay between 2.6 and 13.6 ng/L urine. A set of 16 samples from normally exposed adults was analyzed using this HPLC-fluorescence detection method. Results were comparable with those reported in other studies. The chromatographic separation of the method was transferred to an ultra-high-performance liquid chromatography pentafluorophenyl core-shell column and coupled to a high-resolution time-of-flight mass spectrometer (HR-TOF-MS). The resulting method was used to demonstrate the applicability of LC-HR-TOF-MS for simultaneous target and suspect screening of monohydroxylated polycyclic aromatic hydrocarbons in extracts of urine and particulate matter.

The determination of polycyclic aromatic hydrocarbons in human urine by high-resolution gas chromatography-mass spectrometry.

Polycyclic aromatic hydrocarbons (PAHs), organic compounds formed by at least two condensed aromatic rings, are ubiquitous environmental pollutants that are produced by incomplete combustion of organic materials. PAHs have been classified as carcinogenIC to humans by the International Agency for Research on Cancer, because they can bind to DNA, causing mutations. Therefore, the levels of PAHs in human urine can be used as an indicator for potential carcinogenesis and cell mutation. An analytical method was developed for the accurate measurement of PAHs in urine using high-resolution gas chromatography-mass spectrometry. Urine samples were extracted by an Oasis HLB extraction cartridge after enzymatic hydrolysis with a β-glucuronidase/arylsulfatase cocktail. The 18 PAHs were separated using an Agilent DB-5 MS capillary column (30 m × 0.25 mm, 0.25 μm) and monitored by time-of-flight mass spectrometry. Under the optimized method, the linearity of calibration curves was >0.994. The limits of detection at a signal-to-noise ratio of 3 were 10-100 ng/L. The coefficients of variation were in the range of 0.4-9.0%. The present method was highly accurate for simultaneous determination of 18 PAHs in human urine and could be applied to monitoring and biomedical investigations to check exposure of PAHs.

Urinary 1-hydroxypyrene and smoking are determinants of LINE-1 and AhRR promoter methylation in coke oven workers

Coke oven emissions (COE) containing polycyclic aromatic hydrocarbons (PAHs) are predominant toxic constituents of particulate air pollution that have been linked to increased risk of lung cancer. Aberrant DNA methylation is one of the best known epigenetic changes in human cancers and healthy subjects exposed to carcinogens. The purpose of this study is to explore the factors influencing the methylation of long interspersed nuclear element-1 (LINE-1) and aryl-hydrocarbon receptor repressor (AhRR) in coke oven workers. The study population is composed by coke oven workers (348) and water treatment workers (131). And their urinary PAH metabolites were analyzed by high performance liquid chromatography; DNA methylation were measured by pyrosequencing. The urinary PAHs metabolites were significantly elevated in coke oven workers (P < 0.01). The results from multivariate logistic regression analysis showed that a high level of urinary 1-hydroxypyrene was associated with a significantly increased risk of hypomethylation of LINE-1 (OR: 1.80; 95% CI: 1.25, 2.60), and heavy smoking was associated with a significantly increased risk of hypomethylation of AhRR (OR: 1.44; 95% CI: 1.04, 2.00). Our findings demonstrate that urinary 1-hydroxypyrene may be a useful biomarker for evaluating the role of PAHs exposure on hypomethylation of LINE-1 among coke oven workers and that smoking may be an important factor affecting hypomethylation of AhRR.

Investigating the robustness and extraction performance of a matrix-compatible solid-phase microextraction coating in human urine and its application to assess 2-6-ring polycyclic aromatic hydrocarbons using GC-MS/MS.

In this work, a polydimethylsiloxane/divinylbenzene fiber overcoated with a layer of polydimethylsiloxane was evaluated as analytical sampling tool for the first time in human urine. Urinary polycyclic aromatic hydrocarbons with 2-6 aromatic rings were considered as target compounds. The analyte uptake in kinetic and thermodynamic regime was evaluated and compared to the performances of polydimethylsiloxane/divinylbenzene and polydimethylsiloxane fibers. The assessment of the robustness and endurance of the overcoated fiber was carried out by direct immersion solid-phase microextraction in undiluted urine performing up to 120 consecutive extractions. The overcoated fiber was then used to develop a fast and easy direct immersion solid-phase microextraction with gas chromatography and triple quadrupole mass spectrometry protocol for the quantification of the target polycyclic aromatic hydrocarbons. The attained values of accuracy and precision were 75-114% and 2-19%, respectively, while the limits of quantification ranged between 0.05 and 1ng/L. The proposed protocol was applied to the screening of urine samples collected from smoking and nonsmoking volunteers. The successful results obtained by using the overcoated fiber create not only new alternatives for polycyclic aromatic hydrocarbon exposure assessment but also new perspectives for the application of direct immersion solid-phase microextraction to the analysis of bioclinical matrixes.

Urinary polycyclic aromatic hydrocarbon metabolites, Club cell secretory protein and lung function

BackgroundExposure to polycyclic aromatic hydrocarbons (PAHs) has been associated with lung function decline. However, the underlying mechanisms for the association remain unclear. ObjectivesTo explore potential role of a lung epithelial biomarker, Club cell secretory protein (CC16), in associations between PAH exposures and lung function decline. MethodsWe investigated 3384 adults from the Wuhan-Zhuhai cohort, and followed up at three years after first examination. Linear mixed models was used to quantify dose-response relationships between urinary monohydroxylated PAH metabolites (OH-PAHs) and lung function, as well as OH-PAHs and plasma CC16. Mediation analysis was conducted to investigate role of CC16 in the association between OH-PAHs and lung function. We also estimated the relationships between OH-PAHs and lung function change in three years among participants with different levels of CC16. ResultsEach 1-unit increase of log-transformed total urinary high and low molecular weight OH-PAHs (∑HMW OH-PAH and ∑LMW OH-PAHs) were associated with a 22.59 and 25.25ml reduction of FEV1 respectively, while∑HMW OH-PAH was associated with a 30.38ml reduction of FVC. Moreover, these negative associations between OH-PAHs and lung function levels were significant only among low CC16 group (<15.83ng/ml). CC16 concentration decreased monotonically with increased high molecular weight OH-PAHs (∑HMW OH-PAHs) when ∑HMW OH-PAH concentration was over 0.67μg/mmol Cr. CC16 mediated 22.13% of the association between ∑HMW OH-PAH and FVC among individuals with higher ∑HMW OH-PAH. After three years of follow-up, subjects with low level of plasma CC16 had a significant decline of FVC when exposed to high level of ∑HMW OH-PAH. ConclusionsCC16 play an important role in the association between high molecular weight PAHs and FVC. Individuals with low plasma CC16 level might suffer a decline in lung function when exposed to high level of high molecular weight PAHs.

Prenatal urinary polycyclic aromatic hydrocarbon metabolites, global DNA methylation in cord blood, and birth outcomes: A cohort study in China.

Prenatal exposure to polycyclic aromatic hydrocarbons (PAHs) is a potential risk factor for adverse birth outcomes. Epigenetic mechanisms may play a key role in which PAHs exert its effects. Our study aimed to examine whether prenatal PAH exposure was associated with adverse birth outcomes and altered DNA methylation and to explore potential mediating roles of DNA methylation. Ten urinary PAH metabolites were measured from 106 pregnant women during late pregnancy in a Chinese cohort study. Cord blood DNA methylation in long interspersed nucleotide element-1 (LINE-1) and Alu repetitive elements as surrogates of global DNA methylation was analyzed by bisulfite pyrosequencing. Multivariable linear regression was used to estimate the associations of urinary PAH metabolites with birth outcomes and DNA methylation, and a mediation analysis was also conducted. Prenatal urinary 2-hydroxynaphthalene (2-OHNa), ∑OHNa (sum of 1- and 2-OHNa), and sum of monohydroxy-PAH (∑OH-PAHs) were associated with lower birth length (e.g.,-0.80%, 95% CI:-1.39%,-0.20% for the third vs. first tertile of 2-OHNa; p for trend=0.01). Prenatal urinary 2-OHNa and 1-hydroxyphenanthrene (1-OHPh) were associated with lower Alu and LINE-1 methylation (e.g.,-1.88%, 95% CI:-3.73%,-0.10% for the third vs. first tertile tertile of 2-OHNa in Alu methylation; p for trend=0.04). Mediation analysis failed to show a mediator effect of global DNA methylation in the association between prenatal urinary OH-PAHs and birth outcomes. Prenatal specific PAH exposures are associated with decreased birth length and global DNA methylation. However, global DNA methylation does not mediate the associations of prenatal PAH exposure with birth outcomes. Further studies are needed to confirm the results.

Associations of urinary polycyclic aromatic hydrocarbon metabolites with fractional exhaled nitric oxide and exhaled carbon monoxide: A cross-sectional study

Exposure to Polycyclic aromatic hydrocarbons (PAHs) has been associated with inflammatory responses. Fractional exhaled nitric oxide (FeNO) and exhaled carbon monoxide (eCO) are both important inflammatory mediators especially in airways. However, few studies have investigated associations of PAH exposures with FeNO or eCO. Therefore, we aimed to quantify the associations of urinary PAH metabolites with FeNO and eCO levels, and investigate their potential effect modifiers by linear mixed models among 4133 participants from the Wuhan-Zhuhai cohort in China. We further performed stratified analyses to estimate effect modification. We found significant associations of increased urinary PAH metabolites with elevated eCO and FeNO. Among all participants, each 1% increase of 1-hydroxynaphthalene, 2-hydroxynaphthalene, 2-hydroxyfluorene, 4-hydroxyphenanthrene, 3-hydroxyphenanthrene, and total PAH metabolites was significantly associated with a 12.6% (95% confidence interval: 9.3%, 15.9%), 9.7% (6.5%, 12.9%), 7.5% (4.1%, 10.9%), 3.2% (0.2%, 6.2%), 2.7% (0.1%, 5.3%), and 6.5% (2.7%, 10.4%) increased eCO level, respectively; while each 1% increase of urinary 1-hydroxynaphthalene, 9-hydroxyphenanthrene, 3-hydroxyphenanthrene, and 2-hydroxyphenanthrene was associated with a −3.0% (−5.8%, −0.2%), 2.9% (0.3%, 5.6%), 3.2% (1.0%, 5.4%), and 4.5% (2.2%, 6.9%) change of FeNO level, respectively. Positive associations between certain urinary PAH metabolites and eCO were observed among both ever-smokers and non-smokers, and the associations were stronger among ever-smokers than that among non-smokers. Increased urinary PAH metabolites were associated with decreased FeNO among ever-smokers and elevated FeNO levels among non-smokers. Our findings suggest that PAH exposures may impair airway through inducing inflammatory response, especially among ever-smokers.