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International Journal of Molecular... Jun 2022Benzo[]pyrene (B[]P) is the main representative of polycyclic aromatic hydrocarbons (PAHs), and has been repeatedly found in the air, surface water, soil, and sediments.... (Review)
Review
Benzo[]pyrene (B[]P) is the main representative of polycyclic aromatic hydrocarbons (PAHs), and has been repeatedly found in the air, surface water, soil, and sediments. It is present in cigarette smoke as well as in food products, especially when smoked and grilled. Human exposure to B[]P is therefore common. Research shows growing evidence concerning toxic effects induced by this substance. This xenobiotic is metabolized by cytochrome P450 (CYP P450) to carcinogenic metabolite: 7β,8α-dihydroxy-9α,10α-epoxy-7,8,9,10-tetrahydrobenzo[]pyrene (BPDE), which creates DNA adducts, causing mutations and malignant transformations. Moreover, B[]P is epigenotoxic, neurotoxic, and teratogenic, and exhibits pro-oxidative potential and causes impairment of animals' fertility. CYP P450 is strongly involved in B[]P metabolism, and it is simultaneously expressed as a result of the association of B[]P with aromatic hydrocarbon receptor (AhR), playing an essential role in the cancerogenic potential of various xenobiotics. In turn, polymorphism of genes determines the sensitivity of the organism to B[]P. It was also observed that B[]P facilitates the multiplication of viruses, which may be an additional problem with the widespread COVID-19 pandemic. Based on publications mainly from 2017 to 2022, this paper presents the occurrence of B[]P in various environmental compartments and human surroundings, shows the exposure of humans to this substance, and describes the mechanisms of its toxicity.
Topics: Animals; Benzo(a)pyrene; COVID-19; Carcinogens; Cytochrome P-450 Enzyme System; DNA Adducts; Humans; Pandemics; Polycyclic Aromatic Hydrocarbons
PubMed: 35683027
DOI: 10.3390/ijms23116348 -
International Journal of Molecular... Dec 2021Epigenetic changes constitute one of the processes that is involved in the mechanisms of carcinogenicity. They include dysregulation of DNA methylation processes,... (Review)
Review
Epigenetic changes constitute one of the processes that is involved in the mechanisms of carcinogenicity. They include dysregulation of DNA methylation processes, disruption of post-translational patterns of histone modifications, and changes in the composition and/or organization of chromatin. Benzo(a)pyrene (BaP) influences DNA methylation and, depending on its concentrations, as well as the type of cell, tissue and organism it causes hypomethylation or hypermethylation. Moreover, the exposure to polyaromatic hydrocarbons (PAHs), including BaP in tobacco smoke results in an altered methylation status of the offsprings. Researches have indicated a potential relationship between toxicity of BaP and deregulation of the biotin homeostasis pathway that plays an important role in the process of carcinogenesis. Animal studies have shown that parental-induced BaP toxicity can be passed on to the F1 generation as studied on marine medaka (), and the underlying mechanism is likely related to a disturbance in the circadian rhythm. In addition, ancestral exposure of fish to BaP may cause intergenerational osteotoxicity in non-exposed F3 offsprings. Epidemiological studies of lung cancer have indicated that exposure to BaP is associated with changes in methylation levels at 15 CpG; therefore, changes in DNA methylation may be considered as potential mediators of BaP-induced lung cancer. The mechanism of epigenetic changes induced by BaP are mainly due to the formation of CpG-BPDE adducts, between metabolite of BaP-BPDE and CpG, which leads to changes in the level of 5-methylcytosine. BaP also acts through inhibition of DNA methyltransferases activity, as well as by increasing histone deacetylases HDACs, i.e., HDAC2 and HDAC3 activity. The aim of this review is to discuss the mechanism of the epigenetic action of BaP on the basis of the latest publications.
Topics: 5-Methylcytosine; Animals; Benzo(a)pyrene; Biotin; Carcinogenesis; DNA Methylation; Epigenesis, Genetic; Epigenomics; Female; Histone Deacetylases; Humans; Pregnancy; Prenatal Exposure Delayed Effects
PubMed: 34948252
DOI: 10.3390/ijms222413453 -
Environment International Oct 2023Environmental benzo(a)pyrene (BaP) and its ultimate metabolite BPDE (benzo(a)pyrene-7,8-dihydrodiol-9,10-epoxide) are universal and inevitable persistent organic...
Environmental benzo(a)pyrene (BaP) and its ultimate metabolite BPDE (benzo(a)pyrene-7,8-dihydrodiol-9,10-epoxide) are universal and inevitable persistent organic pollutants and endocrine disrupting chemicals. Angiogenesis in placental decidua plays a pivotal role in healthy pregnancy. Ferroptosis is a newly identified and iron-dependent cell death mode. However, till now, BaP/BPDE exposure, ferroptosis, defective angiogenesis, and miscarriage have never been correlated; and their regulatory mechanisms have been rarely explored. In this study, we used assays with BPDE-exposed HUVECs (human umbilical vein endothelial cells), decidual tissues and serum samples collected from unexplained recurrent miscarriage and their matched healthy control groups, and placental tissues of BaP-exposed mouse miscarriage model. We found that BaP/BPDE exposure caused ferroptosis and then directly suppressed angiogenesis and eventually induced miscarriage. In mechanism, BaP/BPDE exposure up-regulated free Fe level and promoted lipid peroxidation and also up-regulated MARCHF1 (a novel E3 ligase of GPX4) level to promote the ubiquitination degradation of GPX4, both of which resulted in HUVEC ferroptosis. Furthermore, we also found that GPX4 protein down-regulated the protein levels of VEGFA and ANG-1, two key proteins function for angiogenesis, and thus suppressed HUVEC angiogenesis. In turn, supplement with GPX4 could suppress ferroptosis, recover angiogenesis, and alleviate miscarriage. Moreover, the levels of free Fe and VEGFA in serum might predict the risk of miscarriage. Overall, this study uncovered the crosstalk among BaP/BPDE exposure, ferroptosis, angiogenesis, and miscarriage, discovering novel toxicological effects of BaP/BPDE on human reproductive health. This study also warned the public to avoid exposure to polycyclic aromatic hydrocarbons during pregnancy to effectively prevent adverse pregnancy outcomes.
Topics: Mice; Animals; Pregnancy; Humans; Female; 7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide; Ferroptosis; Abortion, Spontaneous; Benzo(a)pyrene; Endothelial Cells; Placenta; Proteins
PubMed: 37802009
DOI: 10.1016/j.envint.2023.108237 -
Advanced Science (Weinheim,... Sep 2023Cigarette smoke aggravates severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. However, the underlying mechanisms remain unclear. Here, they show...
Cigarette smoke aggravates severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. However, the underlying mechanisms remain unclear. Here, they show that benzo[a]pyrene in cigarette smoke extract facilitates SARS-CoV-2 infection via upregulating angiotensin-converting enzyme 2 (ACE2) and transmembrane protease serine 2 (TMPRSS2). Benzo[a]pyrene trans-activates the promoters of ACE2 and TMPRSS2 by upregulating nuclear receptor subfamily 4 A number 2 (NR4A2) and promoting its binding of NR4A2 to their promoters, which is independent of functional genetic polymorphisms in ACE2 and TMPRSS2. Benzo[a]pyrene increases the susceptibility of lung epithelial cells to SARS-CoV-2 pseudoviruses and facilitates the infection of authentic Omicron BA.5 in primary human alveolar type II cells, lung organoids, and lung and testis of hamsters. Increased expression of Nr4a2, Ace2, and Tmprss2, as well as decreased methylation of CpG islands at the Nr4a2 promoter are observed in aged mice compared to their younger counterparts. NR4A2 knockdown or interferon-λ2/λ3 stimulation downregulates the expression of NR4A2, ACE2, and TMPRSS2, thereby inhibiting the infection. In conclusion, benzo[a]pyrene enhances SARS-CoV-2 infection by boosting NR4A2-induced ACE2 and TMPRSS2 expression. This study elucidates the mechanisms underlying the detrimental effects of cigarette smoking on SARS-CoV-2 infection and provides prophylactic options for coronavirus disease 2019, particularly for the elderly population.
Topics: Aged; Male; Humans; Animals; Mice; COVID-19; SARS-CoV-2; Angiotensin-Converting Enzyme 2; Benzo(a)pyrene; Lung; Nuclear Receptor Subfamily 4, Group A, Member 2; Serine Endopeptidases
PubMed: 37428471
DOI: 10.1002/advs.202300834 -
Seminars in Cancer Biology Nov 2021Humans are often exposed to mixtures of environmental pollutants especially environmental chemical carcinogens, representing a significant environmental health issue.... (Review)
Review
Humans are often exposed to mixtures of environmental pollutants especially environmental chemical carcinogens, representing a significant environmental health issue. However, our understanding on the carcinogenic effects and mechanisms of environmental carcinogen mixture exposures is limited and mostly relies on the findings from studying individual chemical carcinogens. Both arsenic and benzo(a)pyrene (BaP) are among the most common environmental carcinogens causing lung cancer and other types of cancer in humans. Millions of people are exposed to arsenic via consuming arsenic-contaminated drinking water and even more people are exposed to BaP via cigarette smoking and consuming BaP-contaminated food. Thus arsenic and BaP combined-exposure in humans is common. Previous epidemiology studies indicated that arsenic-exposed people who were cigarette smokers had significantly higher lung cancer risk than those who were non-smokers. Since BaP is one of the major carcinogens in cigarette smoke, it has been speculated that arsenic and BaP combined-exposure may play important roles in the increased lung cancer risk observed in arsenic-exposed cigarette smokers. In this review, we summarize important findings and inconsistencies about the co-carcinogenic effects and underlying mechanisms of arsenic and BaP combined-exposure and propose new areas for future studies. A clear understanding on the mechanism of co-carcinogenic effects of arsenic and BaP combined exposure may identify novel targets to more efficiently treat and prevent lung cancer resulting from arsenic and BaP combined-exposure.
Topics: Animals; Arsenic; Benzo(a)pyrene; Carcinogens; Cocarcinogenesis; Humans; Lung Neoplasms
PubMed: 33971262
DOI: 10.1016/j.semcancer.2021.05.002 -
Frontiers in Immunology 2023Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by loss of tolerance to self-antigen, autoantibody production, and abnormal immune response....
BACKGROUND
Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by loss of tolerance to self-antigen, autoantibody production, and abnormal immune response. Cuproptosis is a recently reported cell death form correlated with the initiation and development of multiple diseases. This study intended to probe cuproptosis-related molecular clusters in SLE and constructed a predictive model.
METHODS
We analyzed the expression profile and immune features of cuproptosis-related genes (CRGs) in SLE based on GSE61635 and GSE50772 datasets and identified core module genes associated with SLE occurrence using the weighted correlation network analysis (WGCNA). We selected the optimal machine-learning model by comparing the random forest (RF) model, support vector machine (SVM) model, generalized linear model (GLM), and the extreme gradient boosting (XGB) model. The predictive performance of the model was validated by nomogram, calibration curve, decision curve analysis (DCA), and external dataset GSE72326. Subsequently, a CeRNA network based on 5 core diagnostic markers was established. Drugs targeting core diagnostic markers were acquired using the CTD database, and Autodock vina software was employed to perform molecular docking.
RESULTS
Blue module genes identified using WGCNA were highly related to SLE initiation. Among the four machine-learning models, the SVM model presented the best discriminative performance with relatively low residual and root-mean-square error (RMSE) and high area under the curve (AUC = 0.998). An SVM model was constructed based on 5 genes and performed favorably in the GSE72326 dataset for validation (AUC = 0.943). The nomogram, calibration curve, and DCA validated the predictive accuracy of the model for SLE as well. The CeRNA regulatory network includes 166 nodes (5 core diagnostic markers, 61 miRNAs, and 100 lncRNAs) and 175 lines. Drug detection showed that D00156 (Benzo (a) pyrene), D016604 (Aflatoxin B1), D014212 (Tretinoin), and D009532 (Nickel) could simultaneously act on the 5 core diagnostic markers.
CONCLUSION
We revealed the correlation between CRGs and immune cell infiltration in SLE patients. The SVM model using 5 genes was selected as the optimal machine learning model to accurately evaluate SLE patients. A CeRNA network based on 5 core diagnostic markers was constructed. Drugs targeting core diagnostic markers were retrieved with molecular docking performed.
Topics: Humans; Aflatoxin B1; Autoimmune Diseases; Benzo(a)pyrene; Lupus Erythematosus, Systemic; MicroRNAs; Molecular Docking Simulation; Copper; Apoptosis
PubMed: 37313407
DOI: 10.3389/fimmu.2023.1157196 -
International Journal of Hygiene and... May 2022Refined coal tar sealant (RCTS) emulsions are used to seal the surface of asphalt pavement. Nine of the 22 polycyclic aromatic hydrocarbons (PAHs) evaluated in this...
BACKGROUND
Refined coal tar sealant (RCTS) emulsions are used to seal the surface of asphalt pavement. Nine of the 22 polycyclic aromatic hydrocarbons (PAHs) evaluated in this study are classified as known, probable, or possible human carcinogens. Exposure assessment research for RCTS workers has not been published previously.
OBJECTIVES
The overall objective of this study was to develop a representative occupational exposure assessment of PAH exposure for RCTS workers based on worksite surveys. The specific aims were to: 1) quantify full-shift airborne occupational exposures to PAHs among RCTS workers; 2) quantify workers' dermal exposures to PAHs; 3) quantify biomarkers of PAH exposure in workers' urine; 4) identify specific job titles associated with RCTS exposure; and 5) apply these results to a biological exposure index to assess risk of potential genotoxicity from occupational exposures.
METHODS
A total of twenty-one RCTS workers were recruited from three companies. Personal and area air samples were collected using a modification of NIOSH Method 5515. Dermal exposure was assessed by hand and neck wipes before and after shifts. Twenty-two PAHs were quantified via gas chromatography-mass spectrometry selected ion monitoring. Internal dose was estimated by quantifying select PAH metabolites in pre- and post-shift urine samples using on-line solid phase extraction-high performance liquid chromatography-tandem mass spectrometry.
RESULTS
PAH levels in the worker breathing zones were highest for naphthalene, acenaphthene, and phenanthrene, with geometric means of 52.1, 11.4, and 9.8 μg/m, respectively. Hand wipe levels of phenanthrene, fluoranthene and pyrene were the highest among the 22 PAHs with geometric means of 7.9, 7.7, and 5.5 μg/cm, respectively. Urinary PAH biomarkers for naphthalene, fluorene, phenanthrene, and pyrene were detected in all workers and were higher for post-shift samples than those collected pre-shift. Urinary concentrations of the metabolite 1-hydroxypyrene were greater than the American Conference of Governmental Industrial Hygienists (ACGIH) Biological Exposure Index (BEI) for this metabolite in 89 percent of post-shift samples collected on the final day of the work week or field survey. Statistically significances were found between concentrations of fluorene, naphthalene, and phenanthrene in the breathing zone of workers and their corresponding urinary PAH biomarkers. Workers were placed in two work place exposure groups: applicators and non-applicators. Applicators had higher total PAH concentrations in personal breathing zone (PBZ) air samples than non-applicators and were more likely to have post-shift hand wipe concentrations significantly higher than pre-shift concentrations. Concentrations of post-shift urinary biomarkers were higher, albeit not significantly, for applicators than non-applicators.
CONCLUSIONS
The exposure results from RCTS worker samples cannot be explained by proximal factors such as nearby restaurants or construction. Air and skin concentration levels were substantially higher for RCTS workers than previously published levels among asphalt workers for all PAHs. PAH profiles on skin wipes were more consistent with RCTS sealant product than air samples. Last day post-shift urinary concentrations of 1-hydroxypyrene greatly exceeded the ACGIH BEI benchmark of 2.5 μg/L in 25 of 26 samples, which suggests occupational exposure and risk of genotoxicity. When pyrene and benzo[a]pyrene were both detected, concentration ratios from personal exposure samples were used to calculate the adjusted BEI. Concentrations of 1-hydroxypyrene exceeded the adjusted BEIs for air, hand wipes, and neck wipes in most cases. These results indicate the need to increase safety controls and exposure mitigation for RCTS workers.
Topics: Air Pollutants, Occupational; Biomarkers; Coal Tar; Environmental Monitoring; Fluorenes; Humans; Hydrocarbons; Naphthalenes; Occupational Exposure; Phenanthrenes; Polycyclic Aromatic Hydrocarbons; Pyrenes
PubMed: 35472749
DOI: 10.1016/j.ijheh.2022.113971 -
Biosensors Jul 2022Aggregation-induced emission (AIE) is a unique research topic and property that can lead to a wide range of applications, including cellular imaging, theranostics,... (Review)
Review
Aggregation-induced emission (AIE) is a unique research topic and property that can lead to a wide range of applications, including cellular imaging, theranostics, analyte quantitation and the specific detection of biologically important species. Towards the development of the AIE-active materials, many aromatic moieties composed of tetraphenylethylene, anthracene, pyrene, etc., have been developed. Among these aromatic moieties, pyrene is an aromatic hydrocarbon with a polycyclic flat structure containing four fused benzene rings to provide an unusual electron delocalization feature that is important in the AIE property. Numerous pyrene-based AIE-active materials have been reported with the AIE property towards sensing, imaging and theranostics applications. Most importantly, these AIE-active pyrene moieties exist as small molecules, Schiff bases, polymers, supramolecules, metal-organic frameworks, etc. This comprehensive review outlines utilizations of AIE-active pyrene-based materials on the imaging and theranostics studies. Moreover, the design and synthesis of these pyrene-based molecules are delivered with discussions on their future scopes.
Topics: Polymers; Precision Medicine; Pyrenes
PubMed: 35884351
DOI: 10.3390/bios12070550 -
International Journal of Molecular... Jul 2021Microbial biodegradation is one of the acceptable technologies to remediate and control the pollution by polycyclic aromatic hydrocarbon (PAH). Several bacteria, fungi,... (Review)
Review
Microbial biodegradation is one of the acceptable technologies to remediate and control the pollution by polycyclic aromatic hydrocarbon (PAH). Several bacteria, fungi, and cyanobacteria strains have been isolated and used for bioremediation purpose. This review paper is intended to provide key information on the various steps and actors involved in the bacterial and fungal aerobic and anaerobic degradation of pyrene, a high molecular weight PAH, including catabolic genes and enzymes, in order to expand our understanding on pyrene degradation. The aerobic degradation pathway by PRY-1 and sp. KMS and the anaerobic one, by the facultative bacteria anaerobe sp. JP1 and sp. LZ6 are reviewed and presented, to describe the complete and integrated degradation mechanism pathway of pyrene. The different microbial strains with the ability to degrade pyrene are listed, and the degradation of pyrene by consortium is also discussed. The future studies on the anaerobic degradation of pyrene would be a great initiative to understand and address the degradation mechanism pathway, since, although some strains are identified to degrade pyrene in reduced or total absence of oxygen, the degradation pathway of more than 90% remains unclear and incomplete. Additionally, the present review recommends the use of the combination of various strains of anaerobic fungi and a fungi consortium and anaerobic bacteria to achieve maximum efficiency of the pyrene biodegradation mechanism.
Topics: Klebsiella; Microbial Consortia; Mycobacterium; Oxygen; Pseudomonas; Pyrenes
PubMed: 34360967
DOI: 10.3390/ijms22158202 -
Redox Biology Nov 2023Benzo[α]pyrene (Bap) is recognized as a ubiquitous environmental pollutant among the polycyclic aromatic hydrocarbons (PAHs) class. Previous studies have shown that the...
Benzo[α]pyrene (Bap) is recognized as a ubiquitous environmental pollutant among the polycyclic aromatic hydrocarbons (PAHs) class. Previous studies have shown that the hepatotoxicity of Bap is mainly caused by its metabolites, although it remains unclear whether Bap itself induces such damage. This study integrated metabolomics and chemical proteomics approaches to comprehensively identify the potential target proteins affected by Bap in liver cells. The results from the metabolomics showed that the significant changed metabolites were related with cellular redox homeostasis. CEllular Thermal Shift Assay (CETSA) showed that Bap induced protein thermal displacement of superoxide dismutase 3 (SOD3) and glutathione peroxidase 4 (GPX4), which are closely related to oxidative homeostasis. Further validation through in vitro CETSA and drug affinity response target stability (DARTS) revealed that Bap directly affected the stability of SOD3 and GPX4 proteins. The binding affinities of Bap to the potential target proteins were further evaluated using molecular docking, while the isothermal titration calorimetry (ITC) interaction measurements indicated nanomolar-level Kd values. Importantly, we found that Bap weakened the antioxidant capacity by destroying the activities of SOD3 and GPX4, which provided a new understanding of the mechanism of hepatotoxicity induced by Bap. Moreover, our provided workflow integrating metabolomics and label-free chemical proteomics, can be regarded as a practical way to identify the targets and inter-mechanisms for the various environmental compounds.
Topics: Humans; Benzo(a)pyrene; Proteomics; Molecular Docking Simulation; Superoxide Dismutase; Proteins; Chemical and Drug Induced Liver Injury
PubMed: 37847980
DOI: 10.1016/j.redox.2023.102930