Monohydroxylated Metabolites Of Polycyclic Aromatic Hydrocarbons Research Articles

Cross-sectional and longitudinal associations of PAHs exposure with serum uric acid and hyperuricemia among Chinese urban residents: The potential role of oxidative damage

A few studies found polycyclic aromatic hydrocarbons (PAHs) were associated with serum uric acid (SUA) or hyperuricemia (HUA). However, the longitudinal study is vacant, and the underlying mechanisms remain unclear. We aimed to assess the cross-sectional and longitudinal associations of urinary PAHs metabolites with SUA levels and HUA risk, and explore the mediating effects of oxidative stress and inflammation. 10 urinary mono-hydroxylated PAHs metabolites and SUA levels were measured among 4047 Chinese urban residents at baseline and 1496 individuals at 6-year follow-up. Biomarkers of oxidative damage and inflammation in urine/plasma were determined at baseline. We adopted generalized linear mixed models and logistic regression to assess the associations of PAHs metabolites with SUA and HUA, weighted quantile sum regression and adaptive elastic net regression to evaluate the overall effects of multi-PAHs mixture, and mediation analysis to estimate the mediating roles of the biomarkers. In the cross-sectional study, each 1-unit increase in the ln-transformed values of 2-OHNa, 2-OHFlu, 4-OHPh, 9-OHPh, 3-OHPh, 2-OHPh, ΣOHNa, ΣOHPh, and ΣOHPAHs was associated with a 4.10-, 3.90-, 6.42-, 7.33-, 4.85-, 5.43-, 4.47-, 7.67-, and 5.22-μmol/L increase in SUA, respectively. Meanwhile, each 1-unit increase in the ln-transformed values of 1-OHNa, 2-OHNa, 4-OHPh, 9-OHPh, 3-OHPh, 2-OHPh, ΣOHNa, ΣOHPh, and ΣOHPAHs was associated with a 17, 14, 15, 22, 14, 19, 18, 27, and 21% increment in HUA risk, respectively. After 6 years, individuals with persistent high level of 9-OHPh had a 12.5 μmol/L increase in SUA compared with those with persistent low level. The overall effects of multi-PAHs mixture on SUA and HUA remain positive. 8-hydroxy-deoxyguanosine mediated the associations of PAHs metabolites with SUA and HUA, and the mediated proportion ranged from 5.39% to 15.34%. PAHs exposure was associated with the elevated SUA levels and increased HUA risk, and oxidative DNA damage may be one of the underlying mechanisms.

Prenatal exposure to polycyclic aromatic hydrocarbons and executive functions at school age: Results from a combined cohort study

BackgroundExecutive functions develop rapidly in childhood, enabling problem-solving, focused attention, and planning. Exposures to environmental toxicants in pregnancy may impair healthy executive function development in children. There is increasing concern regarding polycyclic aromatic hydrocarbons (PAHs) given their ability to transfer across the placenta and the fetal blood-brain barrier, yet evidence from epidemiological studies is limited. MethodsWe examined associations between prenatal PAH exposure and executive functions in 814 children of non-smoking mothers from two U.S. cohorts in the ECHO-PATHWAYS Consortium. Seven mono-hydroxylated PAH metabolites were measured in mid-pregnancy urine and analyzed individually and as mixtures. Three executive function domains were measured at age 8–9: cognitive flexibility, working memory, and inhibitory control. A composite score quantifying overall performance was further calculated. We fitted linear regressions adjusted for socio-demographics, maternal health behaviors, and psychological measures, and examined modification by child sex and stressful life events in pregnancy. Bayesian kernel machine regression was performed to estimate the interactive and overall effects of the PAH mixture. ResultsThe results from primary analysis of linear regressions were generally null, and no modification by child sex or maternal stress was indicated. Mixture analyses suggested several pairwise interactions between individual PAH metabolites in varied directions on working memory, particularly interactions between 2/3/9-FLUO and other PAH metabolites, but no overall or individual effects were evident. ConclusionWe conducted a novel exploration of PAH-executive functions association in a large, combined sample from two cohorts. Although findings were predominantly null, the study carries important implications for future research and contributes to evolving science regarding developmental origins of diseases.

Association between polycyclic aromatic hydrocarbons and periodontitis: Results from a large population-based study.

To explore the association between polycyclic aromatic hydrocarbons (PAHs) (measured using urinary metabolites) and periodontitis using data from the National Health and Nutrition Examination Survey 2009-2014. Weighted binary logistic regression, Bayesian kernel machine regression (BKMR) and weighted quantile sum (WQS) regression were used to evaluate independent and joint associations between the six urinary monohydroxylated metabolites of PAHs (OH-PAHs) and periodontitis. In all, 3413 participants were included in this study. All six urinary OH-PAHs were present at higher levels in the periodontitis group compared with the non-periodontitis group (p < .001). Fully adjusted multivariable logistic regressions showed positive associations between the six urinary OH-PAHs and periodontitis (p < .05). Higher concentrations of OH-PAHs were also positively associated with attachment loss, periodontal pocket depth (PPD) and the number of tooth loss. BKMR and WQS regression yielded similar positive associations between OH-PAH mixtures and periodontitis. PAHs and their mixture are positively associated with periodontitis, which may provide novel insights into periodontitis prevention from an environmental exposure perspective.

Maternal and newborn metabolomic changes associated with urinary polycyclic aromatic hydrocarbon metabolite concentrations at delivery: an untargeted approach.

Prenatal exposure to polycyclic aromatic hydrocarbons (PAHs) has been associated with adverse human health outcomes. To explore the plausible associations between maternal PAH exposure and maternal/newborn metabolomic outcomes, we conducted a cross-sectional study among 75 pregnant people from Cincinnati, Ohio. We quantified 8 monohydroxylated PAH metabolites in maternal urine samples collected at delivery. We then used an untargeted high-resolution mass spectrometry approach to examine alterations in the maternal (n = 72) and newborn (n = 63) serum metabolome associated with PAH metabolites. Associations between individual maternal urinary PAH metabolites and maternal/newborn metabolome were assessed using linear regression adjusted for maternal and newborn factors while accounting for multiple testing with the Benjamini-Hochberg method. We then conducted functional analysis to identify potential biological pathways. Our results from the metabolome-wide associations (MWAS) indicated that an average of 1% newborn metabolome features and 2% maternal metabolome features were associated with maternal urinary PAH metabolites. Individual PAH metabolite concentrations in maternal urine were associated with maternal/newborn metabolome related to metabolism of vitamins, amino acids, fatty acids, lipids, carbohydrates, nucleotides, energy, xenobiotics, glycan, and organic compounds. In this cross-sectional study, we identified associations between urinary PAH concentrations during late pregnancy and metabolic features associated with several metabolic pathways among pregnant women and newborns. Further studies are needed to explore the mediating role of the metabolome in the relationship between PAHs and adverse pregnancy outcomes.

Longitudinal association of polycyclic aromatic hydrocarbons and genetic risk with lung function

To quantify the association of polycyclic aromatic hydrocarbons (PAHs) and the polygenic risk score (PRS) with lung function decline, we developed a repeated-measures study with 4681 observations from baseline and 6-year follow-up of the Wuhan–Zhuhai cohort. Lung function and urinary monohydroxylated PAH metabolites (OH-PAHs) were measured for each observation. The PRS was derived from 246 lung function-associated genetic variants weighted by the effect size of the decreasing ratio of forced expiratory volume in 1 s by forced vital capacity (FEV1/FVC). Linear mixed models were used to estimate the longitudinal exposure–response relationships between OH-PAHs and lung function, and to evaluate the interactions between OH-PAHs and PRS on the longitudinal change of lung function. We found that each 1-unit increase in log-transformed values of 9-hydroxyfluorene, 2-hydroxyfluorene, 4-hydroxyphenanthrene, 9-hydroxyphenanthrene, 2-hydroxyphenanthrene, 1-hydroxyphenanthrene, 1-hydroxypyrene, low molecular weight OH-PAHs (ΣLMW–OH–PAHs), and total OH-PAHs (ΣOH-PAHs) was associated with an annual change in FEV1/FVC of −0.140, −0.112, −0.260, −0.300, −0.159, −0.220, −0.145, −0.156, and −0.177 %/year, respectively. Interactions on the annual decline of FEV1/FVC were detected between ΣLMW–OH–PAHs and PRS (−0.010 %/year, 95% confidence interval −0.018 to −0.001, Pint = 0.0228), and between ΣOH-PAHs and PRS (−0.010 %/year, −0.018 to −0.001, Pint = 0.0203). These results indicated that specific and total urinary OH-PAHs were associated with the longitudinal FEV1/FVC decline, and ΣLMW–OH–PAHs as well as ΣOH-PAHs interacted with PRS on the annual decline of FEV1/FVC.

Metabolism and elimination kinetics of mono-hydroxylated PAHs metabolites following single exposure to different combinations of PAH4 in rats.

The metabolism of polycyclic aromatic hydrocarbons (PAHs) and the elimination kinetics of their mono-hydroxylated metabolites (OH-PAHs) following single exposure to different combinations of four PAHs (PAH4) were studied. Male Sprague-Dawley rats were orally exposed to a single dose of benzo[a]pyrene (B[a]P) or PAH2 (B[a]P + chrysene), PAH3 (B[a]P + chrysene + benz[a]anthracene), and PAH4 (B[a]P + chrysene + B[a]A + benzo[b]fluoranthene) with each combination adjusted to the same dose of individual compound. OH-PAHs including 3-hydroxybenzo[a]pyrene, 3-hydroxychrysene, 3-hydroxybenz[a]anthracene, and 1-hydroxypyrene (1-OHP) were detected in serum and urine samples collected at six intervals over a 72-h period post-dosing. The hepatic mRNA levels of cytochrome P450 (CYPs) were determined to ascertain the expression induction of PAHs metabolic enzymes. Results showed OH-PAHs (except 1-OHP) peaked within 8h in serum and were excreted from urine within 24-48 h. The serum and urinary concentration of 3-hydroxybenzo[a]pyrene was significantly increased after PAH4 exposure compared with other PAHs combinations. Inversely, urinary concentration of 3-hydroxychrysene was decreased after PAH4 exposure, and the kinetics of 3-hydroxybenz[a]anthracene or 1-OHP were not different depending on the PAHs combinations. Also, CYPs were markedly induced by PAHs. Notably, the induction levels of CYP1A1 and CYP1B1 were significantly higher after PAH4 exposure compared with B[a]P exposure. The results indicated the metabolism of B[a]P was accelerated after PAH4 exposure which might be partly due to the induction of CYPs. These results confirmed PAHs are rapidly metabolized and suggested potential interactions of PAHs may happen among PAH4 mixture.

The influence of the co-exposure to polycyclic aromatic hydrocarbons and toxic metals on DNA damage in brazilian lactating women and their infants: A cross-sectional study using machine learning approaches

Polycyclic aromatic hydrocarbons (PAHs) and toxic metals are widely spread pollutants of public health concern. The co-contamination of these chemicals in the environment is frequent, but relatively little is known about their combined toxicities. In this context, this study aimed to evaluate the influence of the co-exposure to PAHs and toxic metals on DNA damage in Brazilian lactating women and their infants using machine learning approaches. Data were collected from an observational, cross-sectional study with 96 lactating women and 96 infants living in two cities. The exposure to these pollutants was estimated by determining urinary levels of seven mono-hydroxylated PAH metabolites and the free form of three toxic metals. 8-Hydroxydeoxyguanosine (8-OHdG) levels in the urine were used as the oxidative stress biomarker and set as the outcome. Individual sociodemographic factors were also collected using questionnaires. Sixteen machine learning algorithms were trained using 10-fold cross-validation to investigate the associations of urinary OH-PAHs and metals with 8-OHdG levels. This approach was also compared with models attained by multiple linear regression. The results showed that the urinary concentration of OH-PAHs was highly correlated between the mothers and their infants. Multiple linear regression did not show a statistically significant association between the contaminants and urinary 8OHdG levels. Machine learning models indicated that all investigated variables did not present predictive performance on 8-OHdG concentrations. In conclusion, PAHs and toxic metals were not associated with 8-OHdG levels in Brazilian lactating women and their infants. These novelty and originality results were achieved even after applying sophisticated statistical models to capture non-linear relationships. However, these findings should be interpreted cautiously because the exposure to the studied contaminants was considerably low, which may not reflect other populations at risk.

Prenatal polycyclic aromatic hydrocarbon (PAH) exposure in relation to placental corticotropin releasing hormone (pCRH) in the CANDLE pregnancy cohort.

Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous endocrine-disrupting combustion by-products that have been linked to preterm birth. One possible mechanism is through disruption of placental corticotropin releasing hormone (pCRH), a key hormone implicated in parturition. As an extension of recent research identifying pCRH as a potential target of endocrine disruption, we examined maternal PAH exposure in relation to pCRH in a large, diverse sample. Participants, drawn from the CANDLE cohort, part of the ECHO-PATHWAYS Consortium, completed study visits at 16-29 weeks (V1) and 22-39 weeks (V2) gestation (n=812). Seven urinary mono-hydroxylated PAH metabolites (OH-PAHs) were measured at V1 and serum pCRH at V1 and V2. Associations between individual log-transformed OH-PAHs (as well as two summed PAH measures) and log(pCRH) concentrations across visits were estimated using mixed effects models. Minimally-adjusted models included gestational age and urinary specific gravity, while fully-adjusted models also included sociodemographic characteristics. We additionally evaluated effect modification by pregnancy complications, fetal sex, and maternal childhood trauma history. We observed associations between 2-OH-Phenanthrene (2-OH-PHEN) and rate of pCRH change that persisted in fully adjusted models (β=0.0009, 0.00006, 0.0017), however, positive associations with other metabolites (most notably 3-OH-Phenanthrene and 1-Hydroxypyrene) were attenuated after adjustment for sociodemographic characteristics. Associations tended to be stronger at V1 compared to V2 and we observed no evidence of effect modification by pregnancy complications, fetal sex, or maternal childhood trauma history. In conclusion, we observed modest evidence of association between OH-PAHs, most notably 2-OH-PHEN, and pCRH in this sample. Additional research using serial measures of PAH exposure is warranted, as is investigation of alternative mechanisms that may link PAHs and timing of birth, such as inflammatory, epigenetic, or oxidative stress pathways.

Maternal exposure to urinary polycyclic aromatic hydrocarbons (PAH) in pregnancy and childhood asthma in a pooled multi-cohort study

BackgroundPrenatal exposure to polycyclic aromatic hydrocarbons (PAH) may increase risk of pediatric asthma, but existing human studies are limited. ObjectivesWe estimated associations between gestational PAHs and pediatric asthma in a diverse US sample and evaluated effect modification by child sex, maternal asthma, and prenatal vitamin D status. MethodsWe pooled two prospective pregnancy cohorts in the ECHO PATHWAYS Consortium, CANDLE and TIDES, for an analytic sample of N = 1296 mother–child dyads. Mono-hydroxylated PAH metabolites (OH-PAHs) were measured in mid-pregnancy urine. Mothers completed the International Study on Allergies and Asthma in Childhood survey at child age 4–6 years. Poisson regression with robust standard errors was used to estimate relative risk of current wheeze, current asthma, ever asthma, and strict asthma associated with each metabolite, adjusted for potential confounders. We used interaction models to assess effect modification. We explored associations between OH-PAH mixtures and outcomes using logistic weighted quantile sum regression augmented by a permutation test to control Type 1 errors. ResultsThe sociodemographically diverse sample spanned five cities. Mean (SD) child age at assessment was 4.4 (0.4) years. While there was little evidence that either individual OH-PAHs or mixtures were associated with outcomes, we observed effect modification by child sex for most pairs of OH-PAHs and outcomes, with adverse associations specific to females. For example, a 2-fold increase in 2-hydroxy-phenanthrene was associated with current asthma in females but not males (RRfemale = 1.29 [95 % CI: 1.09, 1.52], RRmale = 0.95 [95 % CI: 0.79, 1.13]; pinteraction = 0.004). There was no consistent evidence of modification by vitamin D status or maternal asthma. DiscussionThis analysis, the largest cohort study of gestational PAH exposure and childhood asthma to date, suggests adverse associations for females only. These preliminary findings are consistent with hypothesized endocrine disruption properties of PAHs, which may lead to sexually dimorphic effects.

Exposure to polycyclic aromatic hydrocarbons and the associations with oxidative stress in waste incineration plant workers from South China.

Waste incineration is one of the most common emission sources of polycyclic aromatic hydrocarbons (PAHs), causing potential occupational exposure in waste incineration workers. However, relative investigations among waste incineration plant workers are still very limited, particularly in China. Therefore, we collected urine specimens from 77 workers in a waste incineration plant as the exposed group, and 101 residents as the control group in Shenzhen, China. Nine mono-hydroxylated PAH metabolites (OH-PAHs) and 8-hydroxy-2'-deoxyguanosine (8-OHdG) were measured, and their internal relationships were explored. The urinary levels of most OH-PAHs and 8-OHdG in the exposed group exhibited high levels versus another group (p<0.05). We found negative associations between OH-PAHs and 8-OHdG in the control group (p<0.05), while most of OH-PAHs were not associated with 8-OHdG in the exposed group, which indicated that the exposure to waste incineration could enlarge the level of individual oxidative stress damage. Nevertheless, PAHs were less likely to trigger obvious health risks in exposed workers through estimation of human intake and exposure risks. This study provides a reference for occupational PAH exposure and strengthen the need of health monitoring among incineration workers.

Urinary monohydroxylated polycyclic aromatic hydrocarbons in the general population from 26 provincial capital cities in China: Levels, influencing factors, and health risks.

Polycyclic aromatic hydrocarbons (PAHs) derived from the incomplete combustion of organic materials are associated with adverse health effects. However, little is known about PAH exposure levels and their influencing factors on a large scale in developing countries. In this study, urinary monohydroxylated metabolites of PAHs (OH-PAHs), including the metabolites of naphthalene, fluorene, phenanthrene, pyrene, chrysene, and benzo[a]pyrene, were measured in 1154 samples in the general population nationwide from 26 provincial capitals in China. Concentrations of OH-PAHs ranged from 1.39 to 228μg/L. OH-Nap, metabolite of naphthalene, was the predominant compound, accounting for 65.1% of totals. People in eastern, southwest and northeast China, such as Shanghai, Kunming, Nanning, and Changchun, suffered more PAH exposure than other regions which might associate with sampling time, living habits of the subjects, and the imbalance of economic development and energy consumption across regions. Urinary OH-PAH concentrations were associated with body mass index, gender, and age, and smoking was the main correlating factor. Inhalation and diet might be the main exposure route of human exposure to PAHs, especially for smokers by inhalation. Hazard indices showed that no subject was exposed to PAHs with potential non-carcinogenic risk. Furthermore, the carcinogenic risk was the most significant health effects, with almost all subjects having carcinogenic risk values higher than the acceptable level of 10-6. Naphthalene and phenanthrene were the main contributors. The results also suggested a possible relationship between PAH exposure and lung cancer in the Chinese population. This first nationwide study on human internal exposure to PAHs provides a large body of scientific information for governmental decision-making about associated human health and the prevention of human exposure to PAHs.

Variability in urinary biomarkers of human exposure to polycyclic aromatic hydrocarbons and its association with oxidative stress.

Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous environmental pollutants. Urinary concentrations of mono-hydroxylated metabolites of PAHs (OH-PAHs) have been used as biomarkers of these chemicals’ exposure in humans. Little is known, however, with regard to intra- and inter-individual variability in OH-PAH concentrations and their association with oxidative stress. We conducted a longitudinal study of measurement of urinary concentrations of 15 OH-PAHs and 7 oxidative stress biomarkers (OSBs) of DNA damage [8-hydroxy-2′-deoxyguanosine (8-OHdG)], lipid [malondialdehyde (MDA) and F2-isoprostanes (PGF2α)] and protein [o,o′ -dityrosine (diY)] peroxidation in 19 individuals for 44 consecutive days. Metabolites of naphthalene (OHNap), fluorene (OHFlu), phenanthrene (OHPhe), and pyrene (OHPyr) were found in >70% of 515 urine samples analyzed, at sum concentrations (∑OH-PAH) measured in the range of 0.46–60 ng/mL. After adjusting for creatinine, OHNap and ∑OH-PAH concentrations exhibited moderate predictability, with intra-class correlation coefficients (ICCs) ranging from 0.359 to 0.760. However, ICC values were low (0.001–0.494) for OHFlu, OHPhe, and OHPyr, which suggested poor predictability for these PAH metabolites. Linear mixed-effects analysis revealed that an unit increase in ∑OH-PAH concentration corresponded to 4.5%, 5.3%, 20%, and 21% increase in respective urinary 8-OHdG, MDA, PGF2α, and diY concentrations, suggesting an association with oxidative damage to DNA, lipids, and proteins. The daily intakes of PAHs, calculated from urinary concentrations of OH-PAHs, were 10- to 100-fold below the current reference doses. This study provides valuable information to design sampling strategies in biomonitoring studies and in assigning exposure classifications of PAHs in epidemiologic studies.

Effects of environmental and lifestyle exposure on urinary polycyclic aromatic hydrocarbon metabolites

TPS 771: Diet and lifestyle, Exhibition Hall, Ground floor, August 26, 2019, 3:00 PM - 4:30 PM Background: Urinary polycyclic aromatic hydrocarbons (PAHs) metabolites which reflect internal level of PAH are commonly used to evaluate exposure-response relationship between PAH exposure and adverse health effects on multiple organ systems. However, potential association of environment PAH exposure and lifestyle to urinary PAH metabolites is unclear. Hence, in this study, we evaluated the effect of four common PAH sources, including cigarette smoking, cooking status, traffic exposure and diet, on the level of urinary monohydroxylated PAH metabolites (OH-PAHs) among residents of urban community in China. Methods: Urinary OH-PAHs were measured among 4092 participants from the Wuhan-Zhuhai cohort. Variables of lifestyle were collected using questionnaire by trained investigators. Linear mixed models were conducted to explore the association between PAH sources and urinary OH-PAHs. Standardized regression coefficients were used to assess the relative importance of PAH sources. Results: The levels of total urinary OH-PAHs (∑OH-PAHs), 1-, 2-hydroxynaphthalene and 2-hydroxyfluorene were significantly positively related to tobacco smoking (P<0.01). The concentrations of ∑OH-PAHs, 1-, 2-hydroxynaphthalene and 9-hydroxyfluorene were significantly positively correlated with dietary intake (P<0.05). Elevated levels of 9-hydroxyfluorene and 1-hydroxyphenanthrene were found among the participants with long traffic time exposure (P<0.05). And 1-hydroxypyrene (1-OHP) was significantly associated with self-cooking (P<0.05). Moreover, urinary total OH-PAHs and hydroxynaphthalene were primarily affected by cigarette smoking, poor ventilation and dietary intake. Poor ventilation in kitchen, traffic exposure and dietary intake contributed most to urinary total hydroxyfluorene and hydroxyphenanthrene. And the most important sources to urinary 1-OHP were self-cooking and traffic exposure. Conclusions: The relationship and contribution to the species of urinary OH-PAHs varied from diverse exposure sources. And secondary ventilation could eliminate PAHs effectively.

Cardiovascular Disease-Related Serum Proteins in Workers Occupationally Exposed to Polycyclic Aromatic Hydrocarbons.

Chimney sweeps have higher incidence and mortality of cardiovascular disease (CVD), likely related to their exposure to polycyclic aromatic hydrocarbons (PAH). In order to identify underlying mechanisms of PAH-related CVD, we here investigated whether PAH exposure was associated with levels of putative CVD-related proteins in serum among currently working chimney sweeps. We enrolled 116 chimney sweeps and 125 unexposed controls, all nonsmoking male workers from Sweden. We measured monohydroxylated PAH metabolites in urine by liquid chromatography coupled to tandem mass spectrometry and a panel of 85 proteins in serum using proximity extension assay. Linear regression analysis adjusted for age and body mass index showed that 25 proteins were differentially expressed between chimney sweeps and the controls (p < .05, adjusted for false discovery rate). Of the 25 proteins, follistatin (FS), prointerleukin-16 (IL-16), and heat shock protein beta-1 (HSP 27) showed positive associations with the monohydroxylated metabolites of PAH in a dose-response manner (p < .05). Pathway and gene ontology analyses demonstrated that the differentially expressed proteins were mainly involved in inflammatory response and immunological functions, such as leukocyte migration, cell movement of leukocytes, and adhesion of immune cells. In conclusion, we found a number of putative CVD-related proteins differentially expressed, between PAH-exposed and unexposed individuals, and mainly involved in inflammation and immune function. Our data warrant protective measures to reduce PAH exposure and longitudinal investigations of the protein profile in chimney sweeps and other occupational groups exposed to PAH.

Dose-response relationships between polycyclic aromatic hydrocarbons exposure and platelet indices

The relations of polycyclic aromatic hydrocarbons (PAHs) exposure with platelet indices remain unclear. Based on the baseline data from the Wuhan-Zhuhai Cohort Study, we used generalized linear model, multivariate logistic regression analysis and restricted cubic splines (RCS) to assess linear and nonlinear relationship of PAHs exposure with platelet indices. The results showed that among Wuhan individuals, there were the non-linear relations between total hydroxynaphthalene (ΣOHNa) and mean platelet volume (MPV) or ratio of mean platelet volume to platelet count (MPVP), total hydrophenanthrene (ΣOHPh) and MPV or platelet distribution width (PDW), the sum concentration of urinary monohydroxylated metabolites of PAHs (ΣOH-PAHs) and ratio of platelet count to lymphocyte count (PLR) or MPVP, 1-hydropyrene (1-OHP) and PLR or PDW. But among Zhuhai individuals, neither linear nor non-linear relations were found between each of OH-PAHs or ΣOH-PAHs and platelet indices. The findings indicate that serum MPV and MPVP may be independent biomarkers of effects of exposing to environmental PAHs on human bodies.

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.

Quantification of urinary mono-hydroxylated metabolites of polycyclic aromatic hydrocarbons by on-line solid phase extraction-high performance liquid chromatography-tandem mass spectrometry.

Human exposure to polycyclic aromatic hydrocarbons (PAHs) can be assessed through monitoring of urinary mono-hydroxylated PAHs (OH-PAHs). Gas chromatography (GC) has been widely used to separate OH-PAHs before quantification by mass spectrometry in biomonitoring studies. However, because GC requires derivatization, it can be time consuming. We developed an on-line solid phase extraction coupled to isotope dilution-high performance liquid chromatography-tandem mass spectrometry (on-line-SPE-HPLC-MS/MS) method for the quantification in urine of 1-OH-naphthalene, 2-OH-naphthalene, 2-OH-fluorene, 3-OH-fluorene, 1-OH-phenanthrene, the sum of 2-OH and 3-OH-phenanthrene, 4-OH-phenanthrene, and 1-OH-pyrene. The method, which employed a 96-well plate platform and on-line SPE, showed good sensitivity (i.e., limits of detection ranged from 0.007 to 0.09ng/mL) and used only 100μL of urine. Accuracy, calculated from the recovery percentage at three spiking levels, varied from 94 to 113%, depending on the analyte. The inter- and intra-day precision, calculated from 20 repeated measurements of two quality control materials, varied from 5.2 to 16.7%. Adequate method performance was also confirmed by acceptable recovery (83-102%) of two NIST standard reference materials (3672 and 3673). This high-throughput on-line-SPE-HPLC-MS/MS method can be applied in large-scale epidemiological studies. Graphical abstract Example LC-MS chromatogram of urinary mono-hydroxylated PAH metabolites.

Co-exposure to polycyclic aromatic hydrocarbons, benzene and toluene and their dose–effects on oxidative stress damage in kindergarten-aged children in Guangzhou, China

Polycyclic aromatic hydrocarbons (PAHs), benzene and toluene (BT) are ubiquitous toxic pollutants in the environment. Children are sensitive and susceptible to exposure to these contaminants. To investigate the potential oxidative DNA damage from the co-exposure of PAHs and BT in children, 87 children (aged 3–6) from a kindergarten in Guangzhou, China, were recruited. Ten urinary PAHs and four BT metabolites, as well as 8-hydroxy-2′-deoxyguanosine (8-OHdG, a biomarker of oxidative DNA damage)in urine, were determined using a liquid chromatography tandem mass spectrometer. The results demonstrated that the levels of PAHs and BT in children from Guangzhou were 2–30 times higher than those in children from the other countries based on a comparison with recent data from the literature. In particular, the difference is more substantial for pyrene and volatile BT. Co-exposure to PAHs and BT could lead to additive oxidative DNA damage. Significant dose–effects were observed between the sum concentration of urinary monohydroxylated metabolites of PAHs (∑OH-PAHs), the sum concentration of the metabolites of BT (∑BT) and 8-OHdG levels. Every one percent increase in urinary PAHs and BT generated 0.33% and 0.02% increases in urinary 8-OHdG, respectively. We also determined that the urinary levels of PAHs and BT were negatively associated with the age of the children. Moreover, significant differences in the levels of ∑OH-PAHs and ∑BT were determined between 3- and 6-year-old children (p<0.05), which may be caused by different metabolism capabilities or inhalation frequencies. In conclusion, exposure to PAHs or BT could lead to oxidative DNA damage, and 8-OHdG is a good biomarker for indicating the presence of DNA damage. There exists a significant dose–effect relationship between PAH exposure, BT exposure and the concentration of 8-OHdG in urine. Toddlers (3–4years old) face a higher burden of PAH and BT exposure compared with older children.

Importance of UDP-Glucuronosyltransferases 2A2 and 2A3 in Tobacco Carcinogen Metabolism

UDP-glucuronosyltransferase A1 (UGT2A1) is expressed in the lung and exhibits activity against polycyclic aromatic hydrocarbons (PAHs), suggesting UGT2A1 involvement in the local metabolism of PAH tobacco carcinogens. The goal of the present study was to investigate the importance of two additional UGT2A enzymes, UGT2A2 and UGT2A3, in tobacco carcinogen metabolism. Real-time polymerase chain reaction suggested that wild-type UGT2A2 had the highest expression in the breast, followed by trachea > larynx > kidney. A novel splice variant of UGT2A2 lacking exon 3 (termed UGT2A2Δexon3) was investigated, with UGT2A2Δexon3 expression determined to be 25-50% that of wild-type UGT2A2 in all tissues examined. UGT2A3 was determined to be well expressed in the liver and colon, followed by pancreas > kidney > lung > tonsil > trachea > larynx. Cell homogenates prepared from human embryonic kidney (HEK)293 cells overexpressing wild-type UGT2A2 (termed UGT2A2_i1) exhibited glucuronidation activity, as observed by reverse-phase ultra-pressure liquid chromatography, against 1-hydroxy-(OH)-pyrene, 1-naphthol, and hydroxylated benzo(a)pyrene metabolites, whereas homogenates prepared from HEK293 cells overexpressing UGT2A3 only showed activity against simple PAHs like 1-OH-pyrene and 1-naphthol. Activity assays showed the UGT2A2Δexon3 protein (termed UGT2A2_i2) exhibited no detectable glucuronidation activity against all substrates examined; however, coexpression studies suggested that UGT2A2_i2 negatively modulates UGT2A2_i1 activity. Both UGT2A2 and UGT2A3 exhibited no detectable activity against complex PAH proximate carcinogens, tobacco-specific nitrosamines, or heterocyclic amines. These data suggest that, although UGT2A1 is the only UGT2A enzyme active against PAH proximate carcinogens (including PAH diols), both UGTs 2A1 and 2A2 play an important role in the local detoxification of procarcinogenic monohydroxylated PAH metabolites.

흡연자와 비흡연자의 소변 중 다환방향족탄화수소(PAHs) 대사체 농도 비교

This study investigated urinary metabolites of polycyclic aromatic hydrocarbons (PAHs) in the urine of smokers and non-smokers by liquid chromatography triple quordrupole tandem mass spectroscopy (LC/MS/MS). Compounds analyzed for urinary biomarkers of PAHs were five mono-hydroxylated PAHs metabolites; 1-naphthol, 2-naphthol, 1-hydroxypyrene(1-OHP), 3-phenanthrol, 2-fluorenol. Urine samples were pretreated by enzymatic hydrolysis and solid phase extraction method. Smokers were composed of 17 men and five women; non-smokers 17 men and 16 women. Smoking increased urinary concentrations of five PAHs metabolites significantly higher than those of nonsmokers. Statistically significant correlations among the five PAHs metabolites were shown. The results suggest that LC/MS/MS technology should be useful in the environmental health discipline.