Levels Of 1-hydroxypyrene Research Articles

Optimization of conditions for the sample preparation using mathematical planning for determination of 1-hydroxypyrene in urine using method of gas chromatography-mass spectrometry

Introduction. Biological monitoring of 1-hydroxypyrene is the most widely used method for evaluating the effects of PAHs on humans. The determination of 1-hydroxypyrene in urine is performed using gas chromatography-mass spectrometry (GC-MS). Material and methods. Sample preparation consists of extracting the analyte from the biological matrix by 2-fold liquid extraction with hexane, evaporation the extract to the dry residue in the nitrogen current, and re-dissolution of the dry residue in the silylating agent BSTFA. We used gas chromatograph Agilent 7890A with an HP-5MS capillary column and a mass-selective detector. 1-hydroxypyrene was identified as trimethyl silane on a mass chromatogram based on the retention time and intensity ratio of the registered ions. Results. Optimization of the conditions for liquid extraction of 1-hydroxypyrene was performed using mathematical planning, varying the mass of magnesium sulfate, the extraction time, and the extraction multiplicity. The planning matrix included eight experiments, and the degree extraction of 1-hydroxypyrene was used as an optimization parameter. Interpretation of the model showed the multiplicity of extraction to contribute more to the formation of the degree of extraction than the mass of magnesium sulfate and the extraction time. Discussion. The proposed method foк the sample preparation, based on the extraction of 1-hydroxypyrene by 2-fold liquid extraction with hexane for 2 min with the addition of 0.5 g of magnesium sulfate to the biological sample, allowed reaching the detection limit of 0.1 ng/ml. The evaluation of metrological characteristics showed RSD of the reproducibility to do not exceed 6.4%, the systematic error is not significant, and the accuracy index in the form of a total error is not higher than 15%. Levels of 1-hydroxypyrene in the urine of aluminum production workers are 53 - 414 times higher than in the control group. Conclusion. The choice of optimal conditions for liquid extraction of 1-hydroxypyrene by mathematical planning allowed developing a method for the determination this analyte in urine by GC-MS for biological monitoring.

Association of Urinary Polycyclic Aromatic Hydrocarbons and Diabetes in Korean Adults: Data from the Korean National Environmental Health Survey Cycle 2 (2012-2014).

PurposeTo investigate the associations between the urinary levels of polycyclic aromatic hydrocarbons (PAHs) and diabetes mellitus in Korean adults.Materials and MethodsWe examined the data of 6478 participants aged ≥19 years from the Korean National Environmental Health Survey (KoNEHS) cycle 2 (2012–2014). The urinary levels of 1-hydroxypyrene (1-OHP), 2-naphthol (2-NAP), 1-hydroxyphenathrene (1-OHPhe), and 2-hydroxyfluorene (2-OHFlu) were measured by gas chromatography-mass spectrometry. Diabetes mellitus was defined as a self-report of physician-diagnosed diabetes mellitus or the use of oral hypoglycemics or insulin. Analyses were adjusted for sex, age, body mass index, household income, alcohol consumption, physical activity, urinary creatinine and cotinine, menopausal status, and quartiles of all other PAHs.ResultsThe prevalence of diabetes was 6.5% in the study population. In men, the geometric means of the 2-NAP and 2-OHFlu levels were higher in participants with diabetes mellitus than in those without diabetes mellitus [4.11 vs 3.26 μg/L (P <0.05) and 0.45 vs 0.40 μg/L (P <0.05), respectively]. In women, the geometric mean of 2-NAP levels was also higher in participants with diabetes mellitus than in those without diabetes mellitus (1.81 vs 0.56 μg/L, P <0.05), but there were no significant differences in geometric means for other PAHs. A higher odds ratio (OR) of diabetes was found in participants with the highest quartiles of urinary 2-NAP [OR 1.83, 95% confidence interval (CI) 1.29–2.60] and 2-OHFlu (OR 1.81, 95% CI 1.10–2.98) than in those with the lowest quartiles.ConclusionThe urinary 2-NAP and 2-OHFlu levels were associated with diabetes mellitus in Korean adults. Further studies are needed to determine a potential causal relationship between PAH exposure and diabetes mellitus and its underlying mechanism.

Contributions of dietary, demographic, disease, lifestyle and other factors in explaining variabilities in concentrations of selected monohydroxylated polycyclic aromatic hydrocarbons in urine: Data for US children, adolescents, and adults

Data from National Health and Nutrition Examination Survey for 2003–2014 for US children aged 6–11 years (N = 2097), adolescents aged 12–19 ears (N = 2642), and adults aged ≥ 20 years (N = 9170) were analyzed to investigate the effects of dietary, demographic, disease, lifestyle, and other factors on concentrations of nine metabolites of polycyclic aromatic hydrocarbons (PAH) in urine. PAHs analyzed were: 1-hydroxynaphthalene, 2-hydroxynaphthalene, 2-hydroxyfluorene, 3-hydroxyfluorene, 9-hydroxyfluorene, 1-hydroxyphenanthrene, 2-hydroxyphenanthrene, 3-hydroxyphenanthrene, and 1-hydroxypyrene. Adults with diabetes were found to have higher adjusted levels of 1-hydroxynaphthalene (4139 vs. 3622 ng/L, p < 0.01) than nondiabetics. Adults with albuminuria had higher adjusted levels of 1-hydroxynaphthalene (4140 vs.3621 ng/L, p < 0.01) and 2-hydroxynaphthalene (6039 vs. 5468 ng/L, p < 0.01) than those without albuminuria. Children with albuminuria had lower adjusted levels of 9-hydroxyfluorene (162 vs. 187 ng/L, p = 0.04), 1-hydroxyphenanthrene (92 vs. 108 ng/L, p < 0.01), and 1-hydroxypyrene (118 vs. 138 ng/L, p < 0.01) than those without albuminuria. The ratios of smoker to nonsmoker adjusted levels for adults varied from a low of 1.4 for 2-hydroxyphenanthrene to a high of 5.6 for 3-hydroxyfluorene. Exposure to environmental tobacco smoke at home was associated with higher levels of most OH-PAHs among children, adolescents, and adults. Consumption of red meat not processed at high temperatures was associated with increased levels of 1-hydroxypyrene (β = 0.00040, p = 0.01), 1-, 2-, and 3-hydroxyphenanthrene, 3-, and 9-hydroxyfluorene. Consumption of red meat processed at high temperatures was associated with increased levels of 2-hydroxynaphthalene (β = 0.00046, p = 0.02) among adults. Consumption of fish processed at high temperatures was associated with decreased levels of 1-hydroxynaphtahlene (β = − 0.00088, p < 0.01), 2-, 3-, and 9-hydroxyfluorene, 1-, 2-, and 3-hydroxyphenanthrene. Among adults, alcohol consumption and caffeine may be associated with increased levels of certain OH-PAHs. Oxidative stress and inflammation associated with exposure to PAHs are associated with albuminuria and have the potential to lead to the development of diabetes.

Oxidative DNA Due to Occupational Exposure to Polycyclic Aromatic Hydrocarbons among Coal Tar Workers

Introduction: Polycyclic Aromatic hydrocarbons (PAHs) are compounds of occupational and environmental concern as they are toxic, carcinogenic, mutagenic, and/or teratogenic (causing birth defects). Occupational exposure during coal tar distillation process may cause numerous symptoms and diseases through generation of coal tar fumes that contain principally polycyclic aromatic hydrocarbons (PAHs). Benzopyrene is the most important member of those PAHs. Aim of work: To assess the health effect due to occupational exposure to PAHs; specifically their effects on DNA damage and oxidative stress status among coal tar workers. Materials and methods: A comparative cross sectional study was carried out on two groups, exposed and unexposed group. The exposed group was consisted of 40 coal tar workers and the unexposed group was also composed of 40 matched individuals not occupationally exposed to coal tar .All examined individuals were subjected to full occupational history and estimation of 1-hydroxypyrene (1-OHPyrene) level in urine, blood levels of Benzopyrene-DNA adducts, oxidative stress enzymes (superoxide dismutase and glutathione peroxidase), Cytochrome P450 and Complete blood picture. Results: There was a statistically significant higher urinary level of 1-OHPyrene and higher blood levels of benzopyrene DNA adducts at the exposed workers compared to unexposed ones, in the other hand there were significant reduction in serum levels of superoxide dismutase and glutathione peroxidase among workers exposed to PAHs compared to the unexposed group that might be consumed by oxidative stress status. Conclusion: Oxidative stress and DNA damage might be one of the pathogenesis that may cause adverse health effects associated with occupational exposure to PAHs among coal tar workers.

Biomass Smoke Exposure Is Associated With Gastric Cancer and Probably Mediated Via Oxidative Stress and DNA Damage: A Case-Control Study.

PURPOSEWe investigated the association between gastric cancer and environmental and dietary exposures. In addition, we explored probable mechanistic pathways for the influence of biomass smoke on gastric carcinogenesis.PATIENTS AND METHODSThe study was conducted in Lusaka, Zambia. Questionnaires were used to collect data on risk factors, whereas enzyme-linked immunosorbent assays and high-performance liquid chromatography were used to measure biologic exposures. Study data were analyzed using contingency tables and logistic regression.RESULTSWe enrolled 72 patients with gastric adenocarcinoma and 244 controls. Gastric cancer was positively associated with rural residence (odds ratio [OR], 2.9; 95% CI, 1.5 to 5.3), poverty (OR, 4.2; 95% CI, 1.9 to 9.1), and daily consumption of processed meat (OR, 6.4; 95% CI, 1.3 to 32) and negatively associated with consumption of green vegetables (OR, 0.2; 95% CI, 0.1 to 0.5). Gastric cancer was also associated with biomass smoke exposure (OR, 3.5; 95% CI, 1.9 to 6.2; P < .0001), an association that was stronger for intestinal-type cancers (OR, 3.6; 95% CI, 1.5 to 9.1; P = .003). Exposure to biomass smoke in controls was associated with higher urinary levels of 8-isoprostane (P < .0001), 8-hydroxydeoxyguanosine (P = .029), and 1-hydroxypyrene (P = .041). Gastric cancer was not associated with biochemical measures of current exposure to aflatoxins or ochratoxins.CONCLUSIONIn Zambia, exposure to biomass smoke, daily consumption of processed meat, and poverty are risk factors for gastric cancer, whereas daily consumption of green vegetables is protective against gastric cancer. Exposure to biomass smoke was associated with evidence of oxidative stress and DNA damage, suggesting mechanistic plausibility for the observed association, and the association was restricted to intestinal-type gastric cancer.

Changes in Cigarettes per Day and Biomarkers of Exposure Among US Adult Smokers in the Population Assessment of Tobacco and Health Study Waves 1 and 2 (2013-2015).

Some studies have found some reduction in tobacco exposure and tobacco-related disease risk with decreased numbers of cigarettes smoked per day (CPD), but biomarker of exposure estimates by change in CPD are generally unavailable for the US population. We analyzed biomarker of exposure data by smoking status from over 1100 adult exclusive daily cigarette smokers in Wave 1 of the Population Assessment of Tobacco and Health (PATH) Study who were either exclusive daily smokers or had quit tobacco use entirely at Wave 2. Wave 1 smoking categories consisted of "very light" (1-4 CPD), "light" (5-9 CPD), "moderate" (10-19 CPD), and "heavy" (20+ CPD), and Wave 2 categories were "quitters" (stopped smoking entirely), exclusive cigarette "reducers" (CPD decreased ≥ 50%), "maintainers" (CPD within 50%-150% of Wave 1 value), and "increasers" (CPD increased ≥ 50%). Complete quitters had significantly lower levels of TNE-2, NNAL, NNN, 2-Fluorene, HPMA, CYMA, and MHB3 at Wave 2 for all Wave 1 CPD categories, and decreases were often large. Moderate "reducers" had lower levels of NNAL and 1-Hydroxypyrene at Wave 2, and heavy "reducers" had lower levels of NNAL, 2-Fluorene, and MHB3. Light "increasers" had higher levels of TNE-2, NNAL, 2-Fluorene, CYMA, and cadmium at Wave 2, and heavy "increasers" had higher levels of NNAL and HPMA. Smoking "reducers" and "increasers" had changes in some biomarker of tobacco exposure levels, but reductions were much greater and more consistent for complete quitters. PATH longitudinal cohort study data show that some exclusive daily cigarette smokers increase or decrease CPD over time. These differences may result in moderate changes in the levels of some biomarkers such as NNAL. Even so, however, reductions in biomarker levels are much greater with complete smoking cessation.

Urinary 1-Hydroxypyrene levels among children with asthma in Chennai, South India

Aim: To explore the potential relationship between exposure to Polycyclic Aromatic Hydrocarbons (PAHs) and asthma exacerbation among children and also to explore the potential exposure sources of PAHs at the household level. Methods: Case-control study was conducted at a tertiary care hospital in Chennai among 60 participants after obtaining approval from the Institutional Ethics Committee. The study was conducted from March till May 2018. Informed consent was obtained from the participants. The participants were included based on their clinical diagnosis of asthma and few participants were as used as control based on no documented history of wheeze and PEFR levels. All the participants were male children aged between 9-12 years and exclusion was done if they were reported to having congenital heart disease, surgery or chronic lung disease. They were interviewed with a standardized questionnaire to ascertain their exposure to PAHs sources. Urinary 1-OHP levels were analyzed using HPLC to determine their exposure. Results: Participants with asthma showed a higher concentration of 1-OHP (7.56mg/g) in their urine. Second-hand exposure to tobacco smoke, consumption of charred or grilled foods, use of indoor air pollutants and exposure to traffic fumes were identified as contributive factors to elevated 1-OHP levels. Conclusion: Exposure sources at household levels may play a major role in exacerbating asthma. Significant PAHs exposure was contributed through dietary habits. Further exposure monitoring studies are needed to quantify the impact of PAH exposure on respiratory health. Keywords: Polycylic Aromatic Hydrocarbons; Asthma; 1-Hydroxypyrene

Comparison of Polycyclic Aromatic Hydrocarbons Exposure Across Occupations Using Urinary Metabolite 1-Hydroxypyrene.

Polycyclic aromatic hydrocarbons (PAHs) are well-known carcinogens causing lung and skin cancers in exposed workers. Certain occupations, such as coke production, have been associated with high PAH exposure; however, the number of occupations tested to date remains small. Here, we sought to compare PAH exposure across a wide range of occupations based on levels of 1-hydroxypyrene (1-OHP), the urinary exposure surrogate of PAHs. We collected urine 1-OHP data from the Korean National Environmental Health Survey (KoNEHS), a nationwide biomonitoring survey. We developed a linear regression model, controlling for sex, age, smoking, and survey cycle, and obtained resulting residuals. Then, we computed the fraction of exceeding the third quartile (Q3) level of residuals for each occupation, which is employed as a relative exposure indicator across occupations. A total of 15 125 measurements derived from three cycles of KoNEHS were used for analysis. The overall geometric means (GMs) and geometric standard deviation (GSD) of urine 1-OHP levels were 0.16 µg g-1 creatinine and 3.07, respectively. Among the sub-major occupational groups, 'construction and mining related elementary occupations' showed the highest fraction (0.45) of exceeding the Q3 level of residuals. Among the minor occupational groups, 'deliverers' showed a high fraction (0.42) of exceeding the Q3 level of residuals, which indicates rapidly growing occupations to be addressed. Our results provide ancillary information regarding PAH exposure across occupations, especially for occupations for which PAH exposure has not been well characterized.

Associations between renal functions and exposure of arsenic and polycyclic aromatic hydrocarbon in adults living near a petrochemical complex

BackgroundThe understanding for the impact of petrochemical pollutants exposure on renal functions is limited. ObjectivesOur study examined the associations between renal functions and pollutants exposure in adult residents living in the vicinity of a petrochemical industry. MethodsWe recruited 2069 adult residents near a big petrochemical complex in Taiwan in 2009–2012, and they were categorized into high exposure (HE) and low exposure (LE) groups based on their address to source by 10 km radius. Study subjects were measured the urinary levels of arsenic, cadmium, mercury, thallium, and 1-hydroxypyrene (1-OHP). The estimated glomerular filtration rate (eGFR) was calculated using the Taiwanese Chronic Kidney Disease Epidemiology Collaboration equation, and the chronic kidney disease (CKD) prevalence and risks were defined according to KDIGO 2012 guidelines. Adjusted generalized linear and logistic regression models were applied to evaluate the associations between petrochemical exposure and renal functions. ResultsSubjects in the HE areas had significantly lower eGFR, higher CKD prevalence, and higher levels of urinary arsenic, cadmium, mercury, thallium and 1-OHP. The closer to complex and high exposure group of study subjects were significantly associated with the decrease in eGFR, higher ORs for CKD and high-intermediate risk of CKD. In addition, the study subjects who had two-fold urinary arsenic and 1-OHP levels were significantly with decreased 0.68 and 0.49 ml/min/1.73 m2 of eGFR, respectively. ConclusionsResiding closer and higher arsenic and polycyclic aromatic hydrocarbon exposure were associated with the renal impairment and risks of CKD among the residential population near the petrochemical industry.

Effects of environmental and lifestyle exposures on urinary levels of polycyclic aromatic hydrocarbon metabolites: A cross-sectional study of urban adults in China

Urinary polycyclic aromatic hydrocarbon (PAH) metabolites, biomarkers of internal PAH exposure, are commonly used to explore the effects of PAH on human health. However, the correlation between environmental PAH exposure and the species or levels of urinary PAH metabolites remains unclear. We collected detailed information on PAH exposure sources, including cigarette smoking, cooking, traffic and diet habits via structured questionnaires, and determined 12 urinary monohydroxylated PAH metabolites (OH-PAHs) among 4092 participants from the Wuhan-Zhuhai cohort. Linear mixed models and generalized linear models were conducted to explore the associations of urinary metabolite levels with single or multiple PAH exposure sources. We also calculated the standardized regression coefficients to further compare the contributions of different sources to urinary OH-PAH levels. Our results showed that increasing levels of urinary 1-, 2-hydroxynaphthalene (1-, 2- OHNa) and 2-hydroxyfluorene (2-OHFlu) were significantly correlated with tobacco smoking (all P < 0.01). The concentrations of 1-, 2- OHNa and 9-hydroxyfluorene (9-OHFlu) were positively correlated with dietary intake (all P < 0.05). Individuals who spent a long time in traffic showed elevated levels of 9-OHFlu and 1-hydroxyphenanthrene (1-OHPh) compared with individuals who spent a short time in traffic (all P < 0.05). Self-cooking was associated only with elevated 1-hydroxypyrene (1-OHP) levels. Moreover, good kitchen ventilation resulted in significantly decreased urinary low-molecular-weight OH-PAH levels. These findings suggested that cigarette smoking, self-cooking, high dietary PAH intake and a long time spent in traffic were associated with increased levels of specific urinary PAH metabolites, and good kitchen ventilation effectively reduced the exposure to low-molecular-weight PAHs in self-cooking participants.

Investigation of Relative Air Contribution in Total Pyrene Intake among Primary School Students in Shiraz, Iran

The present study was conducted to evaluate the total internal intake of pyrene and estimate the relative contribution of air to total absorption rate of this compound in Shiraz, Iran. Sixty ambient air samples were collected every 3 days at two stations to measure particulate-bound polycyclic aromatic hydrocarbons (PAHs) including pyrene. Urine samples were also collected from 120 primary school students to determine 1-hydroxypyrene, as the solely biomarker of pyrene. The total pyrene intake and estimating the relative air contribution in total intake were modeled using concentrations of particulate-bound PAHs and 1-hydroxypyrene levels. The mean total intake of pyrene for students lived in urban and suburban areas were 5.30 and 4.31 μg/day, respectively. The relative contribution of ambient air to total pyrene intake was 0.88% and 0.71%in urban and suburban areas, respectively. The findings indicate that ambient air in Shiraz is not a major source of exposure to and intake of the pyrene.

Association between a urinary biomarker for exposure to PAH and blood level of the acute phase protein serum amyloid A in coke oven workers

BackgroundCoke oven workers are exposed to both free and particle bound PAH. Through this exposure, the workers may be at increased risk of cardiovascular diseases. Systemic levels of acute phase response proteins have been linked to cardiovascular disease in epidemiological studies, suggesting it as a marker of these conditions. The aim of this study was to assess whether there was association between PAH exposure and the blood level of the acute phase inflammatory response marker serum amyloid A (SAA) in coke oven workers.MethodsA total of 87 male Polish coke oven workers from two different plants comprised the study population. Exposure was assessed by means of the individual post-shift urinary excretion of 1-hydroxypyrene, as internal dose of short-term PAH exposure, and by anti-benzo[a]pyrene diolepoxide (anti-B[a]PDE)-DNA), as a biomarker of long-term PAH exposure. Blood levels of acute phase proteins SAA and CRP were measured by immunoassay. C-reactive protein (CRP) levels were included to adjust for baseline levels of SAA.ResultsMultiple linear regression showed that the major determinants of increased SAA levels were urinary 1-hydroxypyrene (beta = 0.56, p = 0.030) and serum CRP levels (beta = 7.08; p < 0.0001) whereas anti-B[a]PDE-DNA, the GSTM1 detoxifying genotype, diet, and smoking were not associated with SAA levels.ConclusionsUrinary 1-hydroxypyrene as biomarker of short-term PAH exposure and serum levels of CRP were predictive of serum levels of SAA in coke oven workers. Our data suggest that exposure of coke oven workers to PAH can lead to increased systemic acute response and therefore potentially increased risk of cardiovascular disease.

A multibiomarker approach to evaluate the effect of polyaromatic hydrocarbon exposure on oxidative and genotoxic damage in tandoor workers.

We conducted a cohort study of tandoor workers to evaluate the relationship between the biomarkers of oxidative and genotoxic damage and exposure to polyaromatic hydrocarbons. A series of oxidative and genotoxic damage biomarkers, including urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG), malondialdehyde (MDA) content, and tail moment (TM) by comet assay, was studied. A total of 76 tandoor workers and 79 demographically matched healthy individuals as controls were included. Our results showed that the tandoor workers had significantly higher urinary levels of 1-hydroxypyrene, urinary 8-OHdG, MDA content, and TM compared with the control population. The concentration of all these biomarkers increased with age in the control population as well as tandoor workers. In tandoor workers, significant variation in MDA, 8-oxodG (8-oxo-2'-deoxyguanosine) and TM concentration was detected between smokers (5.08 ± 1.72 nmol/mL, 16.01 ± 4.94 ng/mg creatinine, and 5.87 ± 0.98 µm, respectively) and nonsmokers (3.84 ± 0.98 nmol/mL, 13.74 ± 3.60 ng/mg creatinine, and 5.32 ± 0.69 µm, respectively). A similar pattern was obtained for the control population. We did not obtain significant variations for alcoholics and tobacco chewers. A significant increase in all these three biomarkers was observed with the increase in the period of work exposure in tandoor workers. Multivariate regression analysis also revealed that urinary 8-oxodG, MDA, and TM were statistically significantly related to age and period of work exposure. Overall, the present study showed that the exposure to wood smoke in tandoor workers under occupational conditions led to increased DNA damage because of oxidative stress and genotoxicity. These biomarkers, therefore, are good indices to assess oxidative DNA damage in these workers exposed to occupational genotoxicants. It is also necessary to make preventive changes in work conditions and lifestyle, which will help these occupational workers to lead a healthy life.

Measurement of urinary 1-aminopyrene and 1-hydroxypyrene as biomarkers of exposure to diesel particulate matter in gold miners

Metabolites of polycyclic aromatic hydrocarbons measured in human samples are often used as biomarkers of exposure to diesel engine exhaust (DEE). The aim of this study was to assess the changes in urinary levels of 1-aminopyrene (1-AP) and 1-hydroxypyrene (1-OHP) and their relationship with Elemental Carbon (EC), as a component of diesel engine exhaust exposure, among a hard-rock gold-mining population. Urine samples were collected at the beginning and end of a 12-hour work shift from 100 underground and above ground gold miners. Miners were fitted with personal exposure monitoring equipment to quantify exposure to DEE, measured as Elemental Carbon (EC), across their 12-hour work shift. General linear regression assessed associations of the post-shift urinary 1-AP and 1-OHP concentrations with EC, controlling for age, gender, the pre-shift biomarker level, Body Mass Index (BMI), days on current shift, time in mining, smoking status and second-hand smoke exposure. The concentrations of 1-AP and 1-OHP increased significantly across a 12-hour mining work shift. Moreover, consistent with the sensitivity analysis, the concentration of 1-AP was significantly associated with EC after adjustments. Urinary 1-OHP, but not 1-AP was significantly associated with current smoking. Urinary 1-AP may be a more robust and specific biomarker of DEE than 1-OHP.

1638-P: Urinary Polycyclic Aromatic Hydrocarbon Concentrations and Risk of Diabetes Mellitus in Korean Adults

Background: Polycyclic aromatic hydrocarbons (PAHs) are a group of environmental chemicals with aromatic rings and are generated by the incomplete combustion of organic materials. A few animal and occupational studies suggested a possible association between PAHs exposure and increased risk of diabetes mellitus. Objectives: We aimed to investigate the associations of urine levels of PAHs with diabetes mellitus in Korean adults. Methods: We examined cross-sectional data from the Korean National Environmental Health Survey (KoNEHS) 2012-2014. The study population consisted of 6478 adult subjects (≥20 years of age) from 400 sampling districts in South Korea. The urinary levels of 1-hydroxypyrene, 2-naphthol, 1-hydroxyphenathrene, and 2-hydroxyfluorene were measured in the study subjects. Analyses were adjusted for gender, age, BMI, household income, alcohol consumption, physical activity, urinary creatinine, and urinary cotinine. Results: We observed a positive association between urinary PAHs and cotinine after adjusting for all covariates. A higher geometric mean value of urinary 2-naphthol was observed in subjects with diabetes mellitus compared with controls (2.67 vs. 2.24 μg/L). There was no significant difference in other urinary PAHs according to the presence of diabetes mellitus. According to the elevation of urinary 2-naphthol quartile, the multivariate-adjusted odds ratio (OR) of diabetes mellitus significantly increased in both male and female adults (P-for-trend &amp;lt;0.05). Compared with subjects with urinary 2-naphthol in the lowest quartile, the OR (95% confidence interval) of diabetes mellitus in those in the highest quartile was 1.8 (1.24-2.63). Conclusions: Urinary 2-naphthol levels were positively associated with diabetes mellitus in Korean general populations. Prospective studies are needed to determine a potential causal relationship between PAHs exposure and diabetes mellitus in human. Disclosure Y. Nam: None. S. Kim: None.

FLT1 hypermethylation is involved in polycyclic aromatic hydrocarbons-induced cell transformation

Coke oven emissions (COEs) are common particle pollutants in occupational environment and the major constituents of COEs are polycyclic aromatic hydrocarbons (PAHs). Previously, we identified aberrant methylation of the fms related tyrosine kinase 1 (FLT1) gene over the course of benzo(a)pyrene (BaP)-induced cell transformation via genome-wide methylation array. To quantify FLT1 methylation, we established a bisulfite pyrosequencing assay and examined the FLT1 hypermethylation in several human cancers. The results revealed that 70.0% (21/30 pairs) of lung cancers harbored hypermethylated FLT1 and concomitant suppression of gene expression compared to the adjacent tissues. This implies that FLT1 hypermethylation might play a role in malignant cell transformation. In addition, FLT1 hypermethylation and gene suppression appeared in primary human lymphocytes in a dose-response manner following COEs treatment. To explore whether FLT1 methylation is correlated with COEs exposure and DNA damage, we recruited 144 male subjects who had been exposed to high levels of COEs and 84 male control subjects. Notably, the FLT1 methylation in peripheral blood lymphocytes (PBLCs) of the COEs-exposed group (19.8 ± 3.2%) was enhanced by 17.9% compared to that of the control group (16.8 ± 2.8%) (P < 0.001). The FLT1 methylation status was positively correlated with urinary 1-hydroxypyrene (1-OHP) levels, an internal exposure marker of PAHs (β = 0.029, 95% CI = 0.010–0.048, P = 0.003) and positively correlated with DNA damage (βOTM = 0.024, 95% CI = 0.007–0.040, P = 0.005; βTail DNA = 0.035, 95% CI = 0.0017–0.054, P < 0.001) indicated by comet assay. Taken together, these findings indicate that FLT1 might be a tumor suppressor, and its hypermethylation might contribute to PAHs-induced carcinogenicity.

Exposure to biomass smoke is associated with an increased expression of circulating miRNA-126 and miRNA-155 in Mexican women: a pilot study

Household air pollution has been associated as a risk factor for cardiovascular diseases (CVD). Therefore, the aim of this study was to assess the expression of vascular inflammation regulators miR-126 and miR-155 in plasma from women that cook with wood and women that cook with liquid petroleum gas (LPG). A cumulative index of exposure to smoke (CIES) was estimated, urinary 1-hydroxypyrene (1-OHP) levels were quantified and miRNAs expression levels were determined by quantitative real-time PCR (qRT-PCR). Biochemical clinical parameters were also evaluated. The average values for CIES and 1-OHP were 140 ± 86.8 hours-years (12.0–270 hours-years) and 0.52 ± 0.45 µmol/mol creatinine, respectively. miR-126 and miR-155 expression levels were significantly higher (p < 0.01) in the wood users compared to LPG users. Besides, we found a significant association (p < 0.01) between miR-126 and miR-155 expression levels and CIES and urinary 1-OHP concentrations. These results contribute to the current evidence about the cardiovascular risk related to biomass smoke exposure, from an epigenetic level.

Urinary levels of 1-hydroxypyrene and health risk assessment in children living in Mexican communities with a high risk of contamination by polycyclic aromatic hydrocarbons (PAHs)

ABSTRACTHealth complications have been associated with polycyclic aromatic hydrocarbons (PAHs) exposure, a widespread environmental pollutants family. Therefore, the objective of this investigation was to develop a probabilistic health risk evaluation (using Monte-Carlo simulation) in an infantile population living in areas with a high risk of pollution by PAHs (indoor wood combustion, brick kiln industry, municipal landfill, and low and high vehicular traffic) in Mexico. Urine samples were obtained from Mexican children (n = 135) and urinary 1-OHP concentrations (used as a PAHs biomarker) were quantified. Highest urinary 1-OHP concentrations were detected in children living in areas that use wood combustion as the principal indoor fuel (3.50 ± 0.95 µg/L). Nevertheless, estimated hazard quotients (HQ) lower than 1 were found in all assessed sites after Monte-Carlo analysis. Although HQ <1.0 (a toxic effect is not expected), more data are necessary to determine the real impact of PAHs exposure on children health status.

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.

A prominent air pollutant, Indeno[1,2,3-cd]pyrene, enhances allergic lung inflammation via aryl hydrocarbon receptor

Chronic exposure to ambient polycyclic aromatic hydrocarbons (PAHs) is associated with asthma, but its regulatory mechanisms remain incompletely defined. We report herein that elevated levels of urinary 1-hydroxypyrene, a biomarker of PAH exposure, were found in asthmatic subjects (n = 39) as compared to those in healthy subjects (n = 43) living in an industrial city of Taiwan, where indeno[1,2,3-cd]pyrene (IP) was found to be a prominent PAH associated with ambient PM2.5. In a mouse model, intranasal exposure of mice with varying doses of IP significantly enhanced antigen-induced allergic inflammation, including increased airway eosinophilia, Th2 cytokines, including IL-4 and IL-5, as well as antigen-specific IgE level, which was absent in dendritic cell (DC)-specific aryl hydrocarbon receptor (AhR)-null mice. Mechanistically, IP treatment significantly altered DC’s function, including increased level of pro-inflammatory IL-6 and decreased generation of anti-inflammatory IL-10. The IP’s effect was lost in DCs from mice carrying an AhR-mutant allele. Taken together, these results suggest that chronic exposure to environmental PAHs may pose a significant risk for asthma, in which IP, a prominent ambient PAH in Taiwan, was shown to enhance the severity of allergic lung inflammation in mice through, at least in part, its ability in modulating DC’s function in an AhR-dependent manner.