Human biomonitoring and reference values of urinary 1-hydroxypyrene among Iranian adults population.

Polycyclic aromatic hydrocarbons (PAHs) are one of the most important environmental pollutants. Urinary concentrations of 1-hydropyren metabolites of PAHs have been used as biomarkers of these chemicals' exposure in humans. This cross-sectional study was conducted on 468 healthy Iranian adults over 25 years old and non-smokers in six provinces who were selected based on the clustering method. Fasting urine sampling and body composition and demographic measurements were performed. Urine samples were analyzed by GC-MS. The analysis included descriptive statistics and analytical statistics using multiple linear regression by Python software. 1-Hydroxypyrene was found in 100% of samples, and the mean (Reference Value 95%) concentration of 1-hydroxypyrene was 6.12 (RV 95%: 20) µg/L and 5.95 (21) µg/gcrt. There was a direct relationship between the amount of body composition (body fat, visceral fat), BMI, and age with the urinary concentrations of 1-hydropyren metabolites, and this relationship was significant for BMI with urinary concentrations of 1-hydropyren metabolites (P = 0.045). The amount of 1-hydroxypyrene in healthy Iranian adults has been higher than in similar studies in other countries. These results provide helpful information regarding the exposure of Iranian adults to 1-hydroxypyrene, and these data can be used to supplement the national reference values of human biomonitoring for the interpretation of biomonitoring results.

External Quality Assurance Schemes (EQUASs) and Inter-laboratory Comparison Investigations (ICIs) for human biomonitoring of polycyclic aromatic hydrocarbon (PAH) biomarkers in urine as part of the quality assurance programme under HBM4EU.

Polycyclic aromatic hydrocarbons (PAHs) were included as priority substances for human biomonitoring (HBM) in the European Human Biomonitoring Initiative (HBM4EU), which intended to harmonise and advance HBM across Europe. For this project, a specific Quality Assurance and Quality Control (QA/QC) programme applying Inter-laboratory Comparison Investigations (ICIs) and External Quality Assurance Schemes (EQUASs) was developed to ensure the comparability and accuracy of participating analytical laboratories. This paper presents the results of four ICI/EQUAS rounds for the determination of 13 PAH metabolites in urine, i.e. 1-naphthol, 2-naphthol, 1,2-dihydroxynaphthalene, 2-, 3- and 9-hydroxyfluorene, 1-, 2-, 3-, 4- and 9-hydroxyphenanthrene, 1-hydroxypyrene and 3-hydroxybenzo(a)pyrene. However, 4 PAH metabolites could not be evaluated as the analytical capacity of participating laboratories was too low. Across all rounds and biomarkers, 86% of the participants achieved satisfactory results, although low limits of quantification were required to quantify the urinary metabolites at exposure levels of the general population. Using high-performance liquid or gas chromatography coupled with mass spectrometry (HPLC-MS; GC-MS) and isotope dilution for calibration as well as performing an enzymatic deconjugation step proved to be favourable for the accurate determination of PAHs in urine. Finally, the HBM4EU QA/QC programme identified an international network of laboratories providing comparable results in the analysis of urinary PAH biomarkers, although covering all parameters initially selected was still too challenging.

Association between serum carcinoembryonic antigen and cardiometabolic risks: Implication for cardiometabolic prevention.

Background: Serum carcinoembryonic antigen (CEA) is a biomarker commonly used to detect colorectal cancer. CEA levels are affected by many factors, including cardiometabolic diseases, such as cardiovascular diseases (CVDs) and diabetes. Cardiometabolic diseases and cancer share a similar pathological inflammatory pathway, which correlates with an unhealthy lifestyle. Hence, establishing an adequate CEA cut-off value might be a valuable reference for developing precision healthcare programs for cardiometabolic disease prevention. This study aimed to investigate the association between cardiometabolic risks and serum CEA and the underlying factors. Methods: A community-based, cross-sectional study was conducted between March and December 2021 on the western coast of Taiwan. Lifestyle data were assessed using a structured questionnaire. The cardiometabolic biomarkers, serum CEA, urine malondialdehyde, and 1-hydroxypyrene were quantified by the central laboratory of the collaborating hospital. Chi-square and binary multivariable logistic regression implemented in R version 4.0.2 were used to identify factors defining the risk of high serum CEA levels. Results: A total of 6,295 adult residents without cancer-related diseases completed the study. The mean age was 48.6 (SD = 16.4) years, 56% were female, 32% had metabolic syndrome, and 23% and 10% had CVDs and diabetes, respectively. Multivariate logistic regression showed that age ≥ 65 years, male sex, alcohol consumption, smoking, infrequent use of dental floss, fewer remaining teeth, CVDs, diabetes, and oxidative stress were significantly associated with serum CEA ≥ 3 ng/mL. The discriminatory performance of the area under the receiver operating characteristic curve was 0.75 (0.73-0.76), showing that this model was suitable for distinguishing high CEA levels. Conclusion: Our findings highlight the importance of understanding cardiometabolic diseases, unhealthy lifestyles, and oxidative stress, which contribute to high serum CEA. This study demonstrates that CEA, a well-known tumor marker, can help the early detection and prevention of cardiometabolic diseases via personalized lifestyle modification.

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

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

Hydroxylated polycyclic aromatic hydrocarbons possess inhibitory activity against alpha-glucosidase: An in vitro study using multispectroscopic techniques and molecular docking.

Alpha-glucosidase (GAA) activity can be affected by exogenous substances. Hydroxylated polycyclic aromatic hydrocarbons (OH-PAHs) are typical metabolites of PAHs that can enter the body through various routes. The effects of 1-hydroxynaphthalene (1-OHNap) and 1-hydroxypyrene (1-OHPyr) on GAA activity and the potential mechanisms were investigated viamultispectroscopic methods and molecular docking. First-order derivative synchronous spectrofluorimetry was successfully applied to analyze the fluorescence quenching of GAA in the GAA-1-OHNap and GAA-1-OHPyr systems. 1-OHNap and 1-OHPyr had strong inhibitory effects on GAA activity. GAA could bind with 1-OHNap and 1-OHPyr in 1:1 mode with binding constants of 3.97 × 104 and 9.42 × 104 L/mol at 298 K. Hydrophobic interactions and hydrogen bonds played pivotal roles in the interactions. 1-OHNap was located closer to the active site of GAA than 1-OHPyr. This work suggests that the disturbance of glycometabolism by exogenous pollutants in the human body is worthy of attention and further investigation.

Exposure to polycyclic aromatic hydrocarbons assessed by biomonitoring of firefighters during fire operations in Germany.

BACKGROUND: Firefighters are exposed to a variety of hazardous substances including carcinogens such as polycyclic aromatic hydrocarbons (PAH) during firefighting. In order to minimize the uptake of such substances into the body, firefighters wear personal protective equipment. Only few data exist from real-life firefighting missions and under common although highly variable exposure scenarios such as fighting fires in residential buildings, outdoor, and vehicle fires. The aim of this study is to assess the levels of 1-Hydroxypyrene (1-OHP) as marker for incorporated PAH during firefighting operations in Germany using biomonitoring methods. METHODS: We analyzed urine samples for 1-OHP from 77 firefighters who reported firefighting operations (with and without creatinine adjustment). Urine samples were collected before (baseline) and, where applicable, after firefighting operations at three time points subsequent (2-4, 6-8, and 12 h). RESULTS: Compared to the baseline measurements, mean 1-OHP concentrations after firefighting missions were doubled (0.14 vs. 0.31 µg/L urine, 0.13 µg/g vs. 0.27 µg/g creatinine) and this increase was observed 2-4 h after firefighting. Firefighting in residential buildings (N = 54) and of outdoor and vehicle fires (N = 17) occurred most frequently, whereas blazes, vegetation fires, and fires in underground facilities (N = 6) were rarely encountered. For residential building fires, a 3-fold increase in mean 1-OPH concentrations was observed, whereas no increase could be observed for outdoor and vehicle fires. The highest increase was observed for firefighters with interior attack missions (0.11 µg/L vs. 0.48 µg/L 1-OHP) despite the use of self-contained breathing apparatus (SCBA). During the suppression of outdoor or vehicle fires using SCBA, again, no increase was observed. Although PAH are taken up during certain firefighting missions, the 1-OHP levels almost entirely remained (in 64 of the 77 reported missions) within the normal range of the German general population, i.e., below the reference levels (95th percentiles) of smokers (0.73 µg/g creatinine) and non-smokers (0.30 µg/g creatine). CONCLUSION: Under study conditions, properly applied protective clothing and wearing of SCBA led to a significant reduction of PAH exposure levels. But there are individual situations in which PAH are increasingly incorporated since the incorporation depends on several factors and can be extremely variable. In contrast to many workplaces with high occupational exposure levels, firefighters are not exposed to PAH on a daily basis. Nevertheless, the possibility of an individual increased cancer risk for a particular firefighter cannot completely be ruled out.

A novel and easy-to-construct polymeric l-glutamic acid-modified sensor for urinary 1-hydroxypyrene detection: Human biomonitoring of polycyclic aromatic hydrocarbons exposure.

1-Hydroxypyrene (1-OHP), a metabolite of polycyclic aromatic hydrocarbons (PAHs), is a frequently used biomarker for assessing human exposure to PAHs. Therefore, the technology that provides a quick, simple, cost-effective, portable, accurate, precise, and reliable test is still in great demand. To the best of our knowledge, the creation of an electrochemical device based on poly(l-glutamic acid)-modified a screen-printed graphene electrode (poly(L-GA)/SPGE) for 1-OHP detection was described for the first time. The developed sensor was simply and rapidly manufactured via only a single step of electropolymerization. All the concerned parameters and electroanalytical conditions were studied to obtain the best performance of the methodology. Under optimal conditions, the 1-OHP sensing provided a linear range of 1-1000 nM with the limits of detection and quantification of 0.95 and 3.16 nM, respectively. Moreover, this developed sensor was successfully utilized by determining 1-OHP in human urine samples. In comparison with conventional methods, this newly proposed electrochemical methodology might be tremendously valuable for 1-OHP evaluation in environmental and occupational applications, leading to the early detection of illness risk linked to PAHs in the human body.

[Association among urinary polycyclic aromatic hydrocarbons metabolites, SAHH activity and H19 expression in coke oven workers].

Objective: To investigate the relationship of polycyclic aromatic hydrocarbons (PAHs) exposure, S-adenosylhomocysteine hydrolase (SAHH) activity and long noncoding RNA H19 gene expression in the urine of coke oven workers. Methods: In September 2019, in a coking plant in Taiyuan City, 146 male workers who had worked in coke oven operations for one year were selected through a completely random sampling method, and their basic personal information was collected by questionnaire survey, and blood and urine samples were collected. The levels of 4 PAHs metabolites 2-hydroxfluorene (2-FLU), 2- hydroxynaphthalene (2-NAP), 9-hydroxyphenanthren (9-PHE), and 1-hydroxypyrene (1-OHP) in urine were detected by high performance liquid chromatography (HPLC) -fluorescence detection method. HPLC-UV detection method was used to detect the content of S-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH) in plasma, and the SAHH activity value was obtained by calculating the ratio. Reverse transcription PCR method was used to determine the H19 gene expression level. Urine levels of 2-FLU, 2-NAP, 9-PHE, and 1-OHP were divided into Q(1), Q(2), Q(3), and Q(4) groups according to quartiles (P(25), P(50), P(75)). Regression, trend test and restricted cubic splines were used to analyze the relationship among PAHs metabolites, SAHH activity, H19 gene expression and their dose-response. Results: The median age of coke oven workers was 39.60 years old, the median length of service was 20.38 years, and the urinary levels of 2-FLU, 2-NAP, 9- PHE, and 1-OHP were 0.29, 0.74, 0.09, and 0.06 µg/mmol Cr, respectively. The levels of 2-FLU, 2-NAP and 9-PHE in the urine of workers were significantly different between groups with different 1-OHP levels (P<0.05). After adjusting for age, length of service, smoking, drinking, and levels of 2-FLU, 2-NAP and 9-PHE, SAHH activity decreased with the increase of urinary 1-OHP level (OR=0.63, 95%CI: 0.41-0.98, P=0.038), showing a nonlinear relationship (P(nonlinear)= 0.030). H19 gene expression increased with the increase of urinary 1- OHP level (OR=1.51, 95%CI: 1.03-2.19, P=0.033), there was a linear relationship (P(trend)= 0.058). The relationship between the other three metabolites in urine and SAHH activity and H19 gene expression was not statistically significant (P>0.05) . Conclusion: Urinary 1-OHP level may be a risk factor for decreased SAHH activity and increased H19 gene expression in coke oven workers.

Joint effects of polycyclic aromatic hydrocarbons, smoking, and XPC polymorphisms on damage in exon 2 of KRAS gene among young coke oven workers.

Genetic polymorphisms may contribute to individual susceptibility to DNA damage induced by environmental exposure. In this study, we evaluate the effects of co-exposure to PAHs, smoking and XPC polymorphisms, alone or combined, on damage in exons. A total of 288 healthy male coke oven workers were enrolled into this study, and urinary 1-hydroxypyrene (1-OH-Pyr) was detected. Base modification in exons of KRAS and BRAF gene, and polymorphisms of XPC were determined in plasma by real-time PCR. We observed 1-OH-Pyr was positively related to damage in exon 2 of KRAS (KRAS-2) and in exon 15 of BRAF (BRAF-15), respectively, and KRAS-2 and BRAF-15 were significantly associated with increased 1-OH-Pyr. A stratified analysis found 1-OH-Pyr was significantly associated with KRAS-2 in both smokers and non-smokers, while 1-OH-Pyr was significantly associated with BRAF-15 only in smokers. Additionally, individuals carrying both rs2228001 G-allele (GG+GT) and rs3731055 GG homozygote (GG) genotype appeared to have more significant effect on KRAS-2. The high levels of 1-OH-Pyr were associated with KRAS-2 only in rs2228001 GG+GT genotype carriers and the high levels of 1-OH-Pyr were associated with KRAS-2 only in rs3731055 GG genotype carriers and the most severe KRAS-2 was observed among subjects carrying all four of the above risk factors. Our findings indicated the co-exposure effect of PAHs and smoking could increase the risk of KRAS-2 by a mechanism partly involving XPC polymorphisms.

Factors Associated with Urinary 1-Hydroxypyrene and Malondialdehyde among Adults near a Petrochemical Factory: Implications for Sex and Lifestyle Modification.

BACKGROUND: The association between the biomarkers of environmental exposure, oxidative stress, and health-related behaviors in community residents living in an endemic viral hepatitis area and near petrochemical industrial complexes remains unclear. From a health promotion perspective, healthcare providers must know what to do for residents concerned about their health and living environment, especially for individual-level and modifiable risk factors. Therefore, we aimed to explore the factors associated with urinary 1-hydroxypyrene (1-OHP) and malondialdehyde (MDA). METHODS: A community-based, cross-sectional study was conducted between July 2018 and February 2019 in western coastal Yunlin County, Taiwan. All participants lived within a 10 km radius of a large petrochemical complex and did not work in the factory. This study was conducted with the local hospital through annual community health screening. Biological samples were collected and biomarkers determined and quantified in the central laboratory of the collaborating hospital. RESULTS: A total of 6335 adult residents completed the study. The mean age was 47.7 (SD = 16) years. Out of the total population, 56.4% were female, 30.1% had metabolic syndrome (MetS), and 16.8% and 14.3% had hepatitis B virus antigen (HBsAg) and hepatitis C virus antibody (anti-HCV) positivity, respectively. The median 1-OHP and MDA level was 0.11 and 0.9 µg/g creatinine with an interquartile range of 0.07-0.18, and 0.4-1.5, respectively. The MDA levels correlated with specific diseases. The multivariable ordinal logistic regression model revealed that female sex, smoking, betel nut use, HBsAg, and anti-HCV positivity were associated with higher 1-OHP levels. In men, MetS was associated with higher 1-OHP levels and regular exercise with lower 1-OHP levels. High MDA levels were associated with smoking, betel nut users, HBsAg, and anti-HCV positivity. CONCLUSIONS: The findings highlight the importance of initiating individualized health promotion programs for residents near petrochemical factories, especially for adults with substance-use and cardiometabolic risk factors. Furthermore, it is crucial to provide further treatment to patients with viral hepatitis.

Environmental endocrine disruptor concentrations in urine samples from Mexican Indigenous women.

The Indigenous communities in Mexico show significant degrees of vulnerability to pollution due to the lack of knowledge of health risks, traditions, low levels of support, and restricted access to healthcare. As a result, exposure to environmental endocrine disruptors increases in these populations through plastic components or indoor air pollution. Therefore, the aim of the study was to evaluate the exposure to phthalate metabolites, 1-hydroxypyrene, and bisphenol A through biomonitoring data from indigenous Mexican women. A total of 45 women from the Tocoy community in San Luis Potosí, Mexico, were included. Urine samples were analyzed for Bisphenol A and 4 phthalate metabolites by ultra-performance liquid chromatography couples to tandem mass spectrometry; additionally, the 1-hydroxypyrene concentrations were evaluated by high-performance liquid chromatography coupled to a fluorescence detector. Among the main pollution sources were the use of plastic containers and burning garbage (98-100%). Indigenous women presented an exposure of 100% to mono-2-ethyl phthalate, mono-n-butyl phthalate, and 1-hydroxypyrene, with a median (25th-75th percentiles) of 17,478 (11,362-37,355), 113.8 (61.7-203.5), and 1.2 (0.9-1.7) µg/g creatinine, respectively. The major findings show urinary mono-2-ethyl phthalate concentrations higher than those measured from other studies. Therefore, these results show an impressive exposure to di(2-ethylhexyl) phthalate in Indigenous women. The current study reflects the absence of regulatory policies in marginalized populations. It highlights the need to design strategies that mitigate exposure and the importance of biological monitoring to evaluate and prevent health risk associated with exposure to environmental endocrine disruptors.

Application of a novel nylon needle filter-based solid-phase extraction device to determination of 1-hydroxypyrene in urine.

In this work, a simple and miniaturized solid-phase extraction device was constructed by connecting a commercial nylon needle filter to a syringe, which was applied for extracting 1-hydroxypyrene from a urine sample via hydrophobic and hydrogen bond interactions. The nylon membrane in the needle filter acted as the solid-phase extraction adsorbent, meanwhile, it filtered the particles in the urine sample. To obtain high extraction efficiency, key parameters influencing extraction recovery were investigated. The entire pretreatment process was accomplished within 5 min under the optimal conditions. By coupling high-performance liquid chromatography-ultraviolet, a rapid, low-cost, and convenient nylon needle filter-based method was established for the analysis of 1-hydroxypyrene in a complex urine matrix. Within the linearity range of 0.2-1000 µg/L, the method exhibited a satisfactory correlation coefficient (R = 0.9999). The limit of detection was 0.06 µg/L, and the recoveries from urine sample spiked with three concentrations (5, 20, and 100 µg/L) ranged from 105.8% to 113.1% with the relative standard deviations less than 6.7% (intra-day, n = 6) and 8.9% (inter-day, n = 4). Finally, the proposed method was successfully applied for detecting 1-hydroxypyrene in urine samples from college students, smokers, gas station workers, and chip factory workers. The detected concentration in actual urine samples ranged from 0.46 to 5.26 µg/L. Taken together, this simple and cost-effective nylon needle filter-based solid-phase extraction device showed an excellent application potential for pretreating hydrophobic analytes from aqueous samples.

The preliminary investigation of potential response biomarkers to PAHs exposure on childhood asthma.

BACKGROUND: Exposure to polycyclic aromatic hydrocarbons (PAHs) is a potential risk factor for asthma prevalence. This study aims to explore whether PAHs exposure is associated with childhood asthma by altering microbial diversity and metabolic profiles. METHODS: Thirty children with asthma and 30 children as control in Nanjing, China were recruited. Urinary 1-hydroxypyrene (1-OHPyr) level was determined by UPLC-Orbitrap-MS as a PAHs exposure biomarker. Logistic regression was conducted to investigate the association between 1-OHPyr and childhood asthma. Microbial diversity was analyzed by 16S rRNA gene sequencing. Metabolic profiles were obtained by UPLC-Orbitrap-MS methods. Differential microbiota and metabolites were screened and selected as response biomarkers or intermediates. Mediation analysis was conducted to assess the association between PAHs and asthma mediated by intermediates. RESULTS: Participating children with and without asthma aged 6.43 ± 2.23 years. The urinary 1-OHPyr level ranged from 0.10 to 1.51 µmol/mol (creatinine corrected) in the participants. The urinary 1-OHPyr level was associated with childhood asthma (OR = 7.21, 95% CI: 1.03-50.42 per 1 µmol/mol unit). Microbial diversity was decreased in the group with asthma and there was a significant shift in the abundance of Proteobacteria (at the phylum level), Veillonella and Prevotella (at the genus level). The enrichment pathway analysis showed that differentially expressed metabolites were involved in purine metabolism, amino acid metabolism, and lipid and fatty acid metabolism. The urinary 1-OHPyr level was associated with the abundance of Actinomyces sp. oral clone IO076 and 7-methylguanine that showed a mediation effect on the association between urinary 1-OHPyr levels and childhood asthma by mediation analysis. CONCLUSIONS: Urinary 1-OHPyr exposure was associated with childhood asthma, microbial diversity, and metabolic profiles. Microbial diversity and metabolic profiles may be intermediates as response biomarkers to PAHs exposure in childhood asthma. Further research is needed to confirm these study results and determine the underlying mechanism.

1-Hydroxypyrene mediates renal fibrosis through aryl hydrocarbon receptor signalling pathway.

BACKGROUND AND PURPOSE: In chronic kidney disease (CKD), patients inevitably reach end-stage renal disease and require renal transplant. Evidence suggests that CKD is associated with metabolite disorders. However, the molecular pathways targeted by metabolites remain enigmatic. Here, we describe roles of 1-hydroxypyrene in mediating renal fibrosis. EXPERIMENTAL APPROACH: We analysed 5406 urine and serum samples from patients with Stage 1-5 CKD using metabolomics, and 1-hydroxypyrene was identified and validated using longitudinal and drug intervention cohorts as well as 5/6 nephrectomised and adenine-induced rats. KEY RESULTS: We identified correlations between the urine and serum levels of 1-hydroxypyrene and the estimated GFR in patients with CKD onset and progression. Moreover, increased 1-hydroxypyrene levels in serum and kidney tissues correlated with decreased renal function in two rat models. Up-regulated mRNA expression of aryl hydrocarbon receptor and its target genes, including CYP1A1, CYP1A2 and CYP1B1, were observed in patients and rats with progressive CKD. Further we showed up-regulated mRNA expression of aryl hydrocarbon receptor and its three target genes, plus up-regulated nuclear aryl hydrocarbon receptor protein levels in mice and HK-2 cells treated with 1-hydroxypyrene, which caused accumulation of extracellular matrix components. Treatment with aryl hydrocarbon receptor short hairpin RNA or flavonoids inhibited mRNA expression of aryl hydrocarbon receptor and its target genes in 1-hydroxypyrene-induced HK-2 cells and mice. CONCLUSION AND IMPLICATIONS: Metabolite 1-hydroxypyrene was demonstrated to mediate renal fibrosis through activation of the aryl hydrocarbon receptor signalling pathway. Targeting aryl hydrocarbon receptor may be an alternative therapeutic strategy for CKD progression.

The association between the urinary biomarkers of polycyclic aromatic hydrocarbons and risk of metabolic syndromes and blood cell levels in adults in a Middle Eastern area.

PURPOSE: Limited studies have been published on the association between the urinary biomarkers of Polycyclic Aromatic Hydrocarbons (PAHs) and risk of Metabolic Syndromes (MetS) and blood cell levels in adults in the Middle East. The present study aimed to evaluate the exposure to PAHs and the distribution of urinary OH-PAH levels in the general population of Shiraz, Iran, as well as, the association between OH-PAHs and the prevalence of MetS and blood cell levels. METHODS: In this study, 200 participants were randomly selected from the adult population, and their first-morning void urine samples were collected. RESULTS: The mean concentrations of 1-OHNap, 2-OHNap, 2-OHFlu, 9-OHPhe, and 1-OHP were 639.8, 332.1, 129, 160.3, and 726.9 ng/g creatinine, respectively. The prevalence of MetS was 26% according to the National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATP III) criteria. The results showed that urinary OH-PAHs, especially 1-OHP, were positively and significantly associated with higher waist circumstance (p < 0.001), triglyceride level (p < 0.001), systolic blood pressure (p < 0.001), diastolic blood pressure (p < 0.001), number of white blood cells (p = 0.041) and red blood cells (p < 0.001). It also caused lower levels of High Density Lipoprotein-Cholesterol (HDL-C). In conclusion, the results emphasized the adverse health effects of PAHs on human health, including obesity, hypertension, dyslipidemia, and decreased number of blood cells. CONCLUSION: Therefore, in order to identify the PAHs sources and to develop methods for decreasing the amount of emissions to the environment, broader researches are needed.

The interaction effects of FEN1 rs174538 polymorphism and polycyclic aromatic hydrocarbon exposure on damage in exon 19 and 21 of EGFR gene in coke oven workers.

Polycyclic aromatic hydrocarbon (PAH) exposure and genetic susceptibility were conductive to genotoxic effects including gene damage, which can increase mutational probability. We aimed to explore the dose-effect associations of PAH exposure with damage of exons of epidermal growth factor receptor (EGFR) and breast cancer susceptibility gene 1 (BRCA1), as well as their associations whether modified by Flap endonuclease 1 (FEN1) genotype. Two hundred eighty-eight coke oven male workers were recruited, and we detected the concentration of 1-hydroxypyrene (1-OH-pyr) as PAH exposure biomarker in urine and examined base modification in exons of EGFR and BRCA1 respectively, and genotyped FEN1 rs174538 polymorphism in plasma. We found that the damage indexes of exon 19 and 21 of EGFR (EGFR-19 and EGFR-21) were both significantly associated with increased urinary 1-OH-pyr (both Ptrend < 0.001). The levels of urinary 1-OH-pyr were both significantly associated with increased EGFR-19 and EGFR-21 in both smokers and nonsmokers (both P < 0.001). Additionally, we observed that the urinary 1-OH-pyr concentrations were linearly associated with both EGFR-19 and EGFR-21 only in rs174538 GA+AA genotype carriers (both P < 0.001). Moreover, FEN1rs rs174538 showed modifying effects on the associations of urinary 1-OH-pyr with EGFR-19 and EGFR-21 (both Pinteraction < 0.05). Our findings revealed the linear dose-effect association between exon damage of EGFR and PAH exposure and highlight differences in genetic contributions to exon damage and have the potential to identify at-risk subpopulations who are susceptible to adverse health effects induced by PAH exposure.

Benchmark dose analysis for PAHs hydroxyl metabolites in urine based on mitochondrial damage of peripheral blood leucocytes in coke oven workers in China.

OBJECTIVES: The aim was to explore the dose-response relationship between occupational polycyclic aromatic hydrocarbons (PAHs) exposure and mitochondrial damage in coke oven plants workers. METHODS: 544 workers and 238 healthy people were recruited. The ultra-high performance liquid chromatography was used to determine the level of 1-hydroxypyrene, 1-hydroxynaphthalene, 2-hydroxynaphthalene and 3-hydroxyphenanthrene. The real-time fluorescence quantitative polymerase chain reaction was used to determine the mitochondrial DNA copy number (mtDNAcn). The benchmark dose software was used to analyze the benchmark dose. RESULTS: The mtDNAcn in the exposure group was lower than that in the control group. The concentrations of 1-hydroxypyrene, 1-hydroxynaphthalene, 2-hydroxynaphthalene and 3-hydroxyphenanthrene in the exposure group were higher than those in the control group. There is a dose-response relationship between 1-hydroxypyrene, 3-hydroxyphenanthrene and mitochondrial DNA damage. The benchmark dose lower confidence limit (BMDL) of 1-hydroxypyrene were 0.045, 0.004, and 0.058 pg/µg creatinine in the total, male, and female population, respectively. The BMDL of 3-hydroxyphenanthrene were 5.142, 6.099, and 2.807 pg/µg creatinine in the total, male, and female population, respectively. CONCLUSIONS: The BMDL of 1-hydroxypyrene and 3-hydroxyphenanthrene initially explored can provide a reference to establish occupational exposure biological limits.

Exposure and Absorption of PAHs in Wildland Firefighters: A Field Study with Pilot Interventions.

OBJECTIVES: There is limited knowledge of exposure to polycyclic aromatic hydrocarbons (PAHs) in wildland firefighters, or of the effectiveness of interventions to reduce this. This study of wildland firefighters assessed whether PAHs were present and considered respiratory protection and enhanced skin hygiene as possible interventions. METHODS: 1-Hydroxypyrene (1-HP) was measured in urine samples collected pre-shift, post-shift, and next morning from wildland firefighters in Alberta and British Columbia. Skin wipes, collected pre- and post-shift, were analysed for eight PAHs. Breathing zone air samples were analysed for 11 PAHs. As pilot interventions, participants were randomized to either normal or enhanced skin hygiene. A sample of volunteers was assigned to a disposable N95 mask or a half facepiece mask with P100 organic vapour cartridge. Participants completed a brief questionnaire on activities post-shift and respiratory symptoms. RESULTS: Non-smoking firefighters (66 male and 20 female) were recruited from 11 fire crews. Air sampling pumps were carried for the full shift by 28 firefighters, 25 firefighters wore masks (14 N95 and 11 P100); 42 were assigned to the enhanced skin hygiene intervention. Sixty had hot spotting as their main task. Air monitoring identified PAHs (benzo(b,j,k)fluoranthene in particulates, phenanthrene in the gaseous phase) for 6 of the 11 crews. PAHs (largely naphthalene) were found post-shift on 40/84 skin wipes from the hand and 38/84 from jaw/throat. The mean increase in 1-HP in urine samples collected after the shift (compared with samples collected before the shift) was 66 ng g-1 creatinine (P < 0.001) with an increase over the shift found for 76% of participants. 1-HP in next morning urine samples was significantly lower than at the end of shift (a reduction of 39.3 ng g-1: P < 0.001). The amount of naphthalene on skin wipes was greater at the end of the shift (post) than at the start (pre). The mean post-pre weight difference of naphthalene on skin wipes taken from the hand was 0.96 ng wipe-1 (P = 0.01) and from the jaw/throat 1.28 ng wipe-1 (P = 0.002). The enhanced skin hygiene intervention lead to a larger reduction in 1-HP between end of shift and next morning urine samples but only for those with naphthalene on skin wipes at the end of shift. The difference in 1-HP concentration in urine samples collected before and after the shift was reduced for those wearing a mask (linear tend P = 0.063, one-sided). In multivariable models, 1-HP at end of shift was related to gaseous phase phenanthrene, estimated from air sampling [ß = 318.2, 95% confidence interval (CI) 67.1-569.2]. Naphthalene on hand skin wipes reflected work in hot spotting during the shift (ß = 0.53, 95% CI 0.22-0.86). CONCLUSIONS: This study provided evidence of PAHs in the air and on the skin of many, but not all, fire crew. Absorbed PAHs, reflected in 1-HP in urine, increased over the shift. Results from the pilot interventions suggest that enhanced skin hygiene would reduce absorption post fire where PAHs had been accumulated on the skin, and that masks could be effective in reducing PAH inhalation exposure. Interventions to reduce PAH absorption are supported by the pilot work reported here and warrant further evaluation across a full fire season.

Potential ability of different types of cyclodextrins to modulate the interaction between bovine serum albumin and 1-hydroxypyrene.

Hydroxylated polycyclic aromatic hydrocarbons (OH-PAHs) can bind with functional biomacromolecules and thus cause toxic effects in vivo. Four types of cyclodextrins (CDs) were selected to explore their potential ability to regulate the bindings between 1-hydroxypyrene (1-OHPyr) and bovine serum albumin (BSA) using multi-spectroscopic methods combined with molecular docking. The results showed that the four CDs caused varied modulating effects on the binding of BSA with 1-OHPyr, and the effects of γ-CD and (2-hydroxypropyl)-ß-CD (HPCD) are the most significant. Specifically, γ-CD and HPCD could significantly reduce the binding affinity between 1-OHPyr and BSA, inhibit the micro-environmental changes of tryptophan residues, and slightly recover the helicity of BSA. The interactions and inclusion behavior of CDs with 1-OHPyr was the main reason why CDs could affect the binding of 1-OHPyr to BSA. The results indicated that γ-CD and HPCD might have potential application value in regulating the toxic effects of OH-PAHs.

OGG1 DNA Repair Gene Polymorphism As a Biomarker of Oxidative and Genotoxic DNA Damage.

Background: Single nucleotide polymorphisms in 8-oxoguanine DNA glycosylase-1 (OGG1) gene modulates DNA repair capacity and functions as one of the first lines of protective mechanisms against 8-hydroxy-2'-deoxyguanosine (8-OHdG) mutagenicity. OGG1-Cys326 gene polymorphism may decrease DNA repair function, causing oxidative stress due to higher oxidative DNA damage. The main purpose of this study was to examine the link of oxidative and genotoxic DNA damage with DNA repair OGG1 gene polymorphism, in charcoal workers exposed to polyaromatic hydrocarbons. Methods: Urinary 8-OHdG excretion (a biomarker of oxidative DNA damage) was determined in both exposed and control populations. Genotyping of OGG1 DNA repair gene in the blood samples of subjects was carried out by PCR-RFLP method. Results: The 8-OHdG urinary concentration was significantly higher (p < 0.05) in the exposed (geometric mean 12.33 ± 3.78) than in the unexposed (geometric mean 7.36 ± 2.29) population. DNA damage, as measured by 8-OHdG and tail moment content, was found to be significantly higher in OGG1 homozygous mutants (mt/mt; 18.81 ± 3.34; 6.04 ± 0.52) as compared to wild-type genotypes (wt/wt; 10.34 ± 2.25; 5.19 ± 2.50) and heterozygous (wt/mt) mutants (12.82 ± 2.81; 6.04 ± 0.93) in the exposed group. Conclusion: We found a significant association of OGG1 heterozygous (wt/mt) and homozygous (mt/mt) variants with oxidative and genotoxic damage, suggesting that these polymorphisms may modulate the effects of polycyclic aromatic hydrocarbons exposure in occupational workers.