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1.
Nat Commun ; 15(1): 4909, 2024 Jun 08.
Article in English | MEDLINE | ID: mdl-38851766

ABSTRACT

Tobacco smoking (TS) is implicated in lung cancer (LC) progression through the development of metabolic syndrome. However, direct evidence linking metabolic syndrome to TS-mediated LC progression remains to be established. Our findings demonstrate that 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone and benzo[a]pyrene (NNK and BaP; NB), components of tobacco smoke, induce metabolic syndrome characteristics, particularly hyperglycemia, promoting lung cancer progression in male C57BL/6 J mice. NB enhances glucose uptake in tumor-associated macrophages by increasing the expression and surface localization of glucose transporter (GLUT) 1 and 3, thereby leading to transcriptional upregulation of insulin-like growth factor 2 (IGF2), which subsequently activates insulin receptor (IR) in LC cells in a paracrine manner, promoting its nuclear import. Nuclear IR binds to nucleophosmin (NPM1), resulting in IR/NPM1-mediated activation of the CD274 promoter and expression of programmed death ligand-1 (PD-L1). Restricting glycolysis, depleting macrophages, or blocking PD-L1 inhibits NB-mediated LC progression. Analysis of patient tissues and public databases reveals elevated levels of IGF2 and GLUT1 in tumor-associated macrophages, as well as tumoral PD-L1 and phosphorylated insulin-like growth factor 1 receptor/insulin receptor (pIGF-1R/IR) expression, suggesting potential poor prognostic biomarkers for LC patients. Our data indicate that paracrine IGF2/IR/NPM1/PD-L1 signaling, facilitated by NB-induced dysregulation of glucose levels and metabolic reprogramming of macrophages, contributes to TS-mediated LC progression.


Subject(s)
B7-H1 Antigen , Benzo(a)pyrene , Disease Progression , Hyperglycemia , Insulin-Like Growth Factor II , Lung Neoplasms , Mice, Inbred C57BL , Nuclear Proteins , Nucleophosmin , Receptor, Insulin , Animals , Lung Neoplasms/metabolism , Lung Neoplasms/pathology , Lung Neoplasms/genetics , Male , Humans , Receptor, Insulin/metabolism , Receptor, Insulin/genetics , Mice , B7-H1 Antigen/metabolism , B7-H1 Antigen/genetics , Hyperglycemia/metabolism , Benzo(a)pyrene/toxicity , Insulin-Like Growth Factor II/metabolism , Insulin-Like Growth Factor II/genetics , Nuclear Proteins/metabolism , Nuclear Proteins/genetics , Nitrosamines/toxicity , Tumor-Associated Macrophages/metabolism , Cell Line, Tumor , Paracrine Communication , Gene Expression Regulation, Neoplastic , Smoking/adverse effects , Macrophages/metabolism
2.
Int J Biol Macromol ; 269(Pt 2): 132216, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38729483

ABSTRACT

Agricultural by-products of sesame are promising bioresources in food processing. This study extracted lignin from the by-products of sesame oil production, namely, the capsules and straw of black and white sesame. Using acid, alkali, and ethanol methods, 12 distinct lignins were obtained to prepare biochar, aiming to investigate both the structural characteristics of lignin-based biochar (LBB) and its ability to remove benzo[a]pyrene (BaP) from sesame oil. The results showed that white sesame straw was the most suitable raw material for preparing biochar. In terms of the preparation method, acid-extracted lignin biochar was more effective in removing BaP than alkaline or ethanol methods. Notably, WS-1LB (white sesame straw acid-extracted lignin biochar) exhibited the highest BaP adsorption efficiency (91.44 %) and the maximum specific surface area (1065.8187 m2/g), characterized by porous structures. The pseudo 2nd and Freundlich models were found to be the best fit for the adsorption kinetics and isotherms of BaP on LBB, respectively, suggesting that a multilayer adsorption process was dominant. The high adsorption of LBB mainly resulted from pore filling. This study provides an economical and highly efficient biochar adsorbent for the removal of BaP in oil.


Subject(s)
Charcoal , Lignin , Sesame Oil , Lignin/chemistry , Charcoal/chemistry , Adsorption , Sesame Oil/chemistry , Benzo(a)pyrene/chemistry , Kinetics
3.
Sci Total Environ ; 933: 173088, 2024 Jul 10.
Article in English | MEDLINE | ID: mdl-38735333

ABSTRACT

Sexual dimorphism in immune responses is an essential factor in environmental adaptation. However, the mechanisms involved remain obscure owing to the scarcity of data from sex-role-reversed species in stressed conditions. Benzo[a]pyrene (BaP) is one of the most pervasive and carcinogenic organic pollutants in coastal environments. In this study, we evaluated the potential effects on renal immunotoxicity of the sex-role-reversed lined seahorse (Hippocampus erectus) toward environmental concentrations BaP exposure. Our results discovered the presence of different energy-immunity trade-off strategies adopted by female and male seahorses during BaP exposure. BaP induced more severe renal damage in female seahorses in a concentration-dependent manner. BaP biotransformation and detoxification in seahorses resemble those in mammals. Benzo[a]pyrene-7,8-dihydrodiol-9,10-oxide (BPDE) and 9-hydroxybenzo[a]pyrene (9-OH-BaP) formed DNA adducts and disrupted Ca2+ homeostasis may together attribute the renal immunotoxicity. Sexual dimorphisms in detoxification of both BPDE and 9-OH-BaP, and in regulation of Ca2+, autophagy and inflammation, mainly determined the extent of renal damage. Moreover, the mechanism of sex hormones regulated sexual dimorphism in immune responses needs to be further elucidated. Collectively, these findings contribute to the understanding of sexual dimorphism in the immunotoxicity induced by BaP exposure in seahorses, which may attribute to the dramatic decline in the biodiversity of the genus.


Subject(s)
Benzo(a)pyrene , Sex Characteristics , Smegmamorpha , Water Pollutants, Chemical , Animals , Benzo(a)pyrene/toxicity , Male , Female , Water Pollutants, Chemical/toxicity , Smegmamorpha/physiology , Inactivation, Metabolic , Kidney/drug effects
4.
Article in English | MEDLINE | ID: mdl-38821675

ABSTRACT

Currently, there is no test system, whether in vitro or in vivo, capable of examining all endpoints required for genotoxicity evaluation used in pre-clinical drug safety assessment. The objective of this study was to develop a model which could assess all the required endpoints and possesses robust human metabolic activity, that could be used in a streamlined, animal-free manner. Liver-on-chip (LOC) models have intrinsic human metabolic activity that mimics the in vivo environment, making it a preferred test system. For our assay, the LOC was assembled using primary human hepatocytes or HepaRG cells, in a MPS-T12 plate, maintained under microfluidic flow conditions using the PhysioMimix® Microphysiological System (MPS), and co-cultured with human lymphoblastoid (TK6) cells in transwells. This system allows for interaction between two compartments and for the analysis of three different genotoxic endpoints, i.e. DNA strand breaks (comet assay) in hepatocytes, chromosome loss or damage (micronucleus assay) and mutation (Duplex Sequencing) in TK6 cells. Both compartments were treated at 0, 24 and 45 h with two direct genotoxicants: methyl methanesulfonate (MMS) and ethyl methanesulfonate (EMS), and two genotoxicants requiring metabolic activation: benzo[a]pyrene (B[a]P) and cyclophosphamide (CP). Assessment of cytochrome activity, RNA expression, albumin, urea and lactate dehydrogenase production, demonstrated functional metabolic capacities. Genotoxicity responses were observed for all endpoints with MMS and EMS. Increases in the micronucleus and mutations (MF) frequencies were also observed with CP, and %Tail DNA with B[a]P, indicating the metabolic competency of the test system. CP did not exhibit an increase in the %Tail DNA, which is in line with in vivo data. However, B[a]P did not exhibit an increase in the % micronucleus and MF, which might require an optimization of the test system. In conclusion, this proof-of-principle experiment suggests that LOC-MPS technology is a promising tool for in vitro hazard identification genotoxicants.


Subject(s)
Hepatocytes , Micronucleus Tests , Mutagenicity Tests , Mutagens , Humans , Hepatocytes/drug effects , Hepatocytes/metabolism , Mutagens/toxicity , Micronucleus Tests/methods , Mutagenicity Tests/methods , Liver/drug effects , Liver/metabolism , Lab-On-A-Chip Devices , DNA Damage/drug effects , Comet Assay/methods , Cyclophosphamide/toxicity , Methyl Methanesulfonate/toxicity , Cell Line , Benzo(a)pyrene/toxicity , Coculture Techniques , Ethyl Methanesulfonate/toxicity , Mutation/drug effects
5.
Environ Int ; 188: 108748, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38763096

ABSTRACT

INTRODUCTION: Endocrine disruptors are compounds of manmade origin able to interfere with the endocrine system and constitute an important environmental concern. Indeed, detrimental effects on thyroid physiology and functioning have been described. Differences exist in the susceptibility of human sexes to the incidence of thyroid disorders, like autoimmune diseases or cancer. METHODS: To study how different hormonal environments impact the thyroid response to endocrine disruptors, we exposed human embryonic stem cell-derived thyroid organoids to physiological concentrations of sex hormones resembling the serum levels of human females post-ovulation or males of reproductive age for three days. Afterwards, we added 10 µM benzo[a]pyrene or PCB153 for 24 h and analyzed the transcriptome changes via single-cell RNA sequencing with differential gene expression and gene ontology analysis. RESULTS: The sex hormones receptors genes AR, ESR1, ESR2 and PGR were expressed at low levels. Among the thyroid markers, only TG resulted downregulated by benzo[a]pyrene or benzo[a]pyrene with the "male" hormones mix. Both hormone mixtures and benzo[a]pyrene alone upregulated ribosomal genes and genes involved in oxidative phosphorylation, while their combination decreased the expression compared to benzo[a]pyrene alone. The "male" mix and benzo[a]pyrene, alone or in combination, upregulated genes involved in lipid transport and metabolism (APOA1, APOC3, APOA4, FABP1, FABP2, FABP6). The combination of "male" hormones and benzo[a]pyrene induced also genes involved in inflammation and NFkB targets. Benzo[a]pyrene upregulated CYP1A1, CYP1B1 and NQO1 irrespective of the hormonal context. The induction was stronger in the "female" mix. Benzo[a]pyrene alone upregulated genes involved in cell cycle regulation, response to reactive oxygen species and apoptosis. PCB153 had a modest effect in presence of "male" hormones, while we did not observe any changes with the "female" mix. CONCLUSION: This work shows how single cell transcriptomics can be applied to selectively study the in vitro effects of endocrine disrupters and their interaction with different hormonal contexts.


Subject(s)
Benzo(a)pyrene , Endocrine Disruptors , Gonadal Steroid Hormones , Polychlorinated Biphenyls , Thyroid Gland , Transcriptome , Humans , Benzo(a)pyrene/toxicity , Polychlorinated Biphenyls/toxicity , Endocrine Disruptors/toxicity , Transcriptome/drug effects , Thyroid Gland/drug effects , Female , Male , Single-Cell Analysis , Human Embryonic Stem Cells/drug effects , Human Embryonic Stem Cells/metabolism
6.
Ecotoxicol Environ Saf ; 278: 116390, 2024 Jun 15.
Article in English | MEDLINE | ID: mdl-38705037

ABSTRACT

Microplastics (MPs) and benzo[a]pyrene (B[a]P) are prevalent environmental pollutants. Numerous studies have extensively reported their individual adverse effects on organisms. However, the combined effects and mechanisms of exposure in mammals remain unknown. Thus, this study aims to investigate the potential effects of oral administration of 0.5µm polystyrene (PS) MPs (1 mg/mL or 5 mg/mL), B[a]P (1 mg/mL or 5 mg/mL) and combined (1 mg/mL or 5 mg/mL) on 64 male SD rats by gavage method over 6-weeks. The results demonstrate that the liver histopathological examination showed that the liver lobules in the combined (5 mg/kg) group had blurred and loose boundaries, liver cord morphological disorders, and significant steatosis. The levels of AST, ALT, TC, and TG in the combined dose groups were significantly higher than those in the other groups, the combined (5 mg/kg) group had the lowest levels of antioxidant enzymes and the highest levels of oxidants. The expression of Nrf2 was lowest and the expression of P38, NF-κB, and TNF-α was highest in the combined (5 mg/kg) group. In conclusion, these findings indicate that the combination of PSMPs and B[a]P can cause the highest levels of oxidative stress and elicit markedly enhanced toxic effects, which cause severe liver damage.


Subject(s)
Benzo(a)pyrene , Liver , Microplastics , Oxidative Stress , Polystyrenes , Rats, Sprague-Dawley , Animals , Oxidative Stress/drug effects , Benzo(a)pyrene/toxicity , Microplastics/toxicity , Male , Polystyrenes/toxicity , Liver/drug effects , Liver/pathology , Rats , Environmental Pollutants/toxicity , Antioxidants/metabolism , NF-kappa B/metabolism , NF-E2-Related Factor 2/metabolism
7.
J Hazard Mater ; 473: 134560, 2024 Jul 15.
Article in English | MEDLINE | ID: mdl-38759404

ABSTRACT

Benzo[a]pyrene (BaP) and its metabolic end product benzo(a)pyren-7,8-dihydrodiol-9,10-epoxide (BPDE), are known toxic environmental pollutants. This study aimed to analyze whether sub-chronic BPDE exposure initiated pulmonary fibrosis and the potential mechanisms. In this work, male C57BL6/J mice were exposed to BPDE by dynamic inhalation exposure for 8 weeks. Our results indicated that sub-chronic BPDE exposure evoked pulmonary fibrosis and epithelial-mesenchymal transition (EMT) in mice. Both in vivo and in vitro, BPDE exposure promoted nuclear translocation of Snail. Further experiments indicated that nuclear factor erythroid 2-related factor 2 (Nrf2) and p62 were upregulated in BPDE-exposed alveolar epithelial cells. Moreover, Nrf2 siRNA transfection evidently attenuated BPDE-induced p62 upregulation. Besides, p62 shRNA inhibited BPDE-incurred Snail nuclear translocation and EMT. Mechanically, BPDE facilitated physical interaction between p62 and Snail in the nucleus, then repressed Snail protein degradation by p62-dependent autophagy-lysosome pathway, and finally upregulated transcriptional activity of Snail. Additionally, aryl hydrocarbon receptor (AhR) was activated in BPDE-treated alveolar epithelial cells. Dual-luciferase assay indicated activating AhR could bind to Nrf2 gene promoter. Moreover, pretreatment with CH223191 or α-naphthoflavone (α-NF), AhR antagonists, inhibited BPDE-activated Nrf2-p62 signaling, and alleviated BPDE-induced EMT and pulmonary fibrosis in mice. Taken together, AhR-mediated Nrf2-p62 signaling contributes to BaP-induced EMT and pulmonary fibrosis.


Subject(s)
Benzo(a)pyrene , Epithelial-Mesenchymal Transition , Mice, Inbred C57BL , NF-E2-Related Factor 2 , Pulmonary Fibrosis , Receptors, Aryl Hydrocarbon , Signal Transduction , Animals , Epithelial-Mesenchymal Transition/drug effects , NF-E2-Related Factor 2/metabolism , Receptors, Aryl Hydrocarbon/metabolism , Pulmonary Fibrosis/chemically induced , Pulmonary Fibrosis/metabolism , Pulmonary Fibrosis/pathology , Benzo(a)pyrene/toxicity , Male , Signal Transduction/drug effects , 7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide/toxicity , Mice , Sequestosome-1 Protein/metabolism , Basic Helix-Loop-Helix Transcription Factors/metabolism
8.
Environ Pollut ; 353: 124150, 2024 Jul 15.
Article in English | MEDLINE | ID: mdl-38735466

ABSTRACT

In the environment, soil colloids are widespread and possess a significant adsorption capacity. This makes them capable of transporting different pollutants, presenting a potential risk to human and ecological well-being. This study aimed to examine the adsorption and co-migration characteristics of benzo(a)pyrene (BaP) and soil colloids in areas contaminated with organic substances, utilizing both static and dynamic batch experiments. In the static adsorption experiments, it was observed that the adsorption of BaP onto soil colloids followed the pseudo-second-order kinetic model (R2 = 0.966), and the adsorption isotherm conformed to the Langmuir model (R2 = 0.995). The BaP and soil colloids primarily formed bonds through π-π interactions and hydrogen bonds. The dynamic experimental outcomes revealed that elevating colloids concentration contributed to increased BaP mobility. Specifically, when the concentration of soil colloids in influent was 500 mg L-1, the mobility of BaP was 23.2 % compared to that without colloids of 13.4 %. Meanwhile, the lowering influent pH value contributed to increased BaP mobility. Specifically, when the influent pH value was 4.0, the mobility of BaP was 30.1 %. The BaP's mobility gradually declined as the initial concentration of BaP in polluted soil increased. Specifically, when the initial concentration of BaP in polluted soil was 5.27 mg kg-1, the mobility of BaP was 39.1 %. This study provides a support for controlling BaP pollution in soil and groundwater.


Subject(s)
Benzo(a)pyrene , Colloids , Soil Pollutants , Soil , Benzo(a)pyrene/chemistry , Colloids/chemistry , Soil Pollutants/chemistry , Adsorption , Soil/chemistry , Water Pollutants, Chemical/chemistry , Kinetics
9.
Chemosphere ; 360: 142384, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38797205

ABSTRACT

Interactions between polycyclic aromatic hydrocarbons (PAHs) and titanium dioxide (TiO2) nanoparticles (NPs) can produce unforeseen photoproducts in the aqueous phase. Both PAHs and TiO2-NPs are well-studied and highly persistent environmental pollutants, but the consequences of PAH-TiO2-NP interactions are rarely explored. We investigated PAH photoproduct formation over time for benzo[a]pyrene (BaP), fluoranthene (FLT), and pyrene (PYR) in the presence of ultraviolet A (UVA) using a combination of analytical and computational methods including, identification of PAH photoproducts, assessment of expression profiles for gene indicators of PAH metabolism, and computational evaluation of the reaction mechanisms through which certain photoproducts might be formed. Chemical analyses identified diverse photoproducts, but all PAHs shared a primary photoproduct, 9,10-phenanthraquinone (9,10-PQ), regardless of TiO2-NP presence. The computed reaction mechanisms revealed the roles photodissociation and singlet oxygen chemistry likely play in PAH mediated photochemical processes that result in the congruent production of 9,10-PQ within this study. Our investigation of PAH photoproduct formation has provided substantial evidence of the many, diverse and congruent, photoproducts formed from physicochemically distinct PAHs and how TiO2-NPs influence bioavailability and time-related formation of PAH photoproducts.


Subject(s)
Nanoparticles , Photochemical Processes , Polycyclic Aromatic Hydrocarbons , Titanium , Ultraviolet Rays , Titanium/chemistry , Polycyclic Aromatic Hydrocarbons/chemistry , Nanoparticles/chemistry , Fluorenes/chemistry , Pyrenes/chemistry , Benzo(a)pyrene/chemistry , Environmental Pollutants/chemistry , Biological Availability
10.
Food Chem ; 452: 139430, 2024 Sep 15.
Article in English | MEDLINE | ID: mdl-38713984

ABSTRACT

As emerging contaminants, microplastics threaten food and environmental safety. Dibutyl phthalate (DBP, released from microplastics) and benzo[a]pyrene (BaP, adsorbed on microplastics) coexisted in food and the environment, harming human health, requesting a sensitive and simultaneous testing method to monitor. To address current sensitivity, simultaneousness, and on-site portability challenges during dual targets in complex matrixes, CuCo2S4/Fe3O4 nanoflower was designed to develop a smartphone-assisted photoelectrochemical point-of-care test (PEC POCT). The carrier transfer mechanism in CuCo2S4/Fe3O4 was proven via density functional theory calculation. Under optimal conditions, the PEC POCT showed low detection limits of 0.126, and 0.132 pg/mL, wide linearity of 0.001-500, and 0.0005-50 ng/mL for DBP and BaP, respectively. The smartphone-assisted PEC POCT demonstrated satisfied recoveries (80.00%-119.63%) in real samples. Coherent results were recorded by comparing the PEC POCT to GC-MS (DBP) and HPLC (BaP). This novel method provides a practical platform for simultaneous POCT for food safety and environment monitoring.


Subject(s)
Electrochemical Techniques , Food Contamination , Microplastics , Smartphone , Food Contamination/analysis , Microplastics/analysis , Electrochemical Techniques/instrumentation , Electrochemical Techniques/methods , Limit of Detection , Environmental Monitoring/instrumentation , Environmental Monitoring/methods , Copper/analysis , Copper/chemistry , Benzo(a)pyrene/analysis , Dibutyl Phthalate/analysis
11.
Chemosphere ; 358: 142242, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38710409

ABSTRACT

The release of polycyclic aromatic hydrocarbons (PAHs) into the environment is posing a threat to ecosystems and human health. Benzo(a)pyrene (BaP) is considered a biomarker of PAH exposure and is classified as a Group 1 carcinogen. However, it was not known whether BaP is mutagenic, i.e. induces inherited germline mutations. In this study, we used a recently established method, which combines short-term mutation accumulation lines (MAL) with whole genome sequencing (WGS) to assess mutagenicity in the non-biting midge Chironomus riparius. The mutagenicity analysis was supplemented by an evaluation of the development of population fitness in three successive generations in the case of chronic exposure to BaP at a high concentration (100 µg/L). In addition, the level of ROS-induced oxidative stress was examined in vivo. Exposure to the higher BaP concentration led to an increase in germline mutations relative to the control, while the lower concentration showed no mentionable effect. Against expectations, BaP exposure decreased ROS-level compared to the control and is thus probably not responsible for the increased mutation rate. Likewise, the higher BaP concentration decreased fitness measured as population growth rate per day (PGR) significantly over all generations, without signs of rapid evolutionary adaptations. Our results thus highlighted that high BaP exposure may influence the evolutionary trajectory of organisms.


Subject(s)
Benzo(a)pyrene , Chironomidae , Oxidative Stress , Animals , Benzo(a)pyrene/toxicity , Chironomidae/drug effects , Chironomidae/genetics , Oxidative Stress/drug effects , Water Pollutants, Chemical/toxicity , Reactive Oxygen Species/metabolism , Whole Genome Sequencing , Mutagens/toxicity , Polycyclic Aromatic Hydrocarbons/toxicity , Mutagenicity Tests
12.
Aquat Toxicol ; 272: 106946, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38759525

ABSTRACT

Microplastics are ubiquitous environmental pollutants frequently detected in aquatic environments. Here we used the Atlantic salmon epithelial gill cell line (ASG-10) to investigate the uptake and effects of polystyrene (PS) microplastic. The ASG-10 cell line has phagocytotic/endocytic capacities and can take up clear PS particles at 0.2 and 1.0 µm, while PS at 10 µm was not taken up. As a response to the uptake, the ASG-10 cells increased their lysosomal activity. Furthermore, no effects on the mitochondria were found, neither on the mitochondrial membrane potential nor the mitochondria morphology (branch length and diameter). Interestingly, even a very high concentration of PS (200 µg/ml) with all tested particle sizes had no effects on cell viability or cell cycle. The environmental toxin Benzo(a)pyrene (B(a)P), a known inducer of CYP1A, is highly hydrophobic and thus sticks to the PS particles. However, co-exposure of B(a)P and PS the particles did not increase the induction of CYP1A activity compared to B(a)P alone. Our study contributes to the understanding of the cellular effects of PS particles using a highly relevant Atlantic salmon gill epithelium in vitro model.


Subject(s)
Epithelial Cells , Gills , Microplastics , Salmo salar , Water Pollutants, Chemical , Animals , Gills/drug effects , Gills/cytology , Microplastics/toxicity , Water Pollutants, Chemical/toxicity , Epithelial Cells/drug effects , Cell Line , Polystyrenes/toxicity , Benzo(a)pyrene/toxicity , Cell Survival/drug effects , Cytochrome P-450 CYP1A1/metabolism , Membrane Potential, Mitochondrial/drug effects , Mitochondria/drug effects , Mitochondria/metabolism
13.
Ecotoxicol Environ Saf ; 278: 116409, 2024 Jun 15.
Article in English | MEDLINE | ID: mdl-38701656

ABSTRACT

Environmental benzo(a)pyrene (BaP) and itsmetabolite benzo(a)pyrene-7, 8-dihydrodiol-9, 10-epoxide (BPDE), classic endocrine disrupting chemical and persistent organic pollutant, could cause miscarriage. However, the detailed mechanisms are still largely unclear and should be further explored. In this study, we discovered that exposure of trophoblast cells with BPDE could suppressed cell invasion/migration by inhibiting MEST/VIM (Vimentin) pathway. Moreover, BPDE exposure also increased lnc-HZ01 expression level, which further inhibited MEST/VIM pathway and then suppressed invasion/migration. Knockdown of lnc-HZ01 or overexpression of MEST could efficiently rescue invasion/migration of BPDE-exposed Swan 71 cells. Furthermore, lnc-HZ01 was highly expressed and MEST/VIM were lowly expressed in recurrent miscarriage (RM) villous tissues compared with healthy control (HC) group. Finally, we also found that BaP exposure inhibited murine Mest/Vim pathway in placental tissues and induced miscarriage in BaP-exposed mice. Therefore, the regulatory mechanisms were similar in BPDE-exposed human trophoblast cells, RM villous tissues, and placental tissues of BaP-exposed mice with miscarriage, building a bridge to connect BaP/BPDE exposure, invasion/migration, and miscarriage. This study provided novel insights in the toxicological effects and molecular mechanisms of BaP/BPDE-induced miscarriage, which is helpful for better elucidating the toxicological risks of BaP/BPDE on female reproduction.


Subject(s)
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide , Benzo(a)pyrene , Cell Movement , Down-Regulation , Trophoblasts , Trophoblasts/drug effects , Female , Animals , Cell Movement/drug effects , Benzo(a)pyrene/toxicity , Humans , Mice , 7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide/toxicity , Pregnancy , Endocrine Disruptors/toxicity , Environmental Pollutants/toxicity , Cell Line , Abortion, Spontaneous/chemically induced
14.
J Environ Sci Health B ; 59(5): 248-262, 2024.
Article in English | MEDLINE | ID: mdl-38605578

ABSTRACT

The ability of Acinetobacter sp. strain HAP1, isolated from petroleum refinery effluent, to eliminate different concentrations (20, 40, 60, 80 and 100 mg/L) of Benzo[a]Pyrene degradation (BaP) was studied. A test to improve this degradation capacity was carried out by culturing the bacterial strain in association with a cyanobacteria. The results show a highly significant effect of the concentration of (BaP) and a very highly significant effect of the symbiosis between the bacterial strain and the cyanobacteria. This combination was able to significantly improve the (BaP) degradation rate by up to 18%. This degradation and especially in association leads to a complete mineralization of (BaP) and there is a difference in yield that can go up to 15%. Through molecular identification based on 16S rRNA gene sequence analysis, strains HAP1 and S66 were recognized as Acinetobacter sp. strain HAP1 and Cyanobacteriota sp. S66, respectively. Comparison of the retrieved sequences with the NCBI GenBank database was done, and the closest matches were found to be Acinetobacter pittii strain JD-10 for bacteria and Pseudochroococcus couteii strain PMC 885.14 for cyanobacteria.


Subject(s)
Acinetobacter , Cyanobacteria , Benzo(a)pyrene , Symbiosis , RNA, Ribosomal, 16S/genetics , Biodegradation, Environmental , Acinetobacter/genetics , Acinetobacter/metabolism
15.
Sci Rep ; 14(1): 9597, 2024 04 26.
Article in English | MEDLINE | ID: mdl-38671174

ABSTRACT

Smoking of classic cigarettes has been well-established as a health risk factor, including cardiovascular, neurological, and pulmonary diseases. Adverse effects on human reproduction have also been shown. Smokers are assumed to have a significantly lower chance of pregnancy, however, the impact of smoking on medically assisted reproduction (MAR) treatment outcomes is controversial. Moreover, smoking habits have changed during the last decades since e-cigarettes and hookahs, or water pipes, have become very popular, yet little is known regarding vaping or hookah-smoking patients undergoing MAR treatments. This prospective study aimed to examine the presence of benzo[a]pyrene, nicotine, and its main metabolite, cotinine, in human follicular fluid (FF) in non-smoking, smoking, and vaping/hookah-smoking patients and to evaluate the impact on female fertility. Human FF samples were collected from 320 women subjected to intracytoplasmic sperm injection (ICSI) cycles due to male subfertility. Gas chromatography combined with mass spectrometry was used to analyse the presence of benzo[a]pyrene, nicotine, and cotinine. A questionnaire was provided to assess patient consumption behaviour and to identify (1) non-smoking patients, (2) patients who consumed cigarettes, and (3) patients with exclusive consumption of e-cigarettes or hookahs. Data were analysed using linear and logistic regression, Fisher's exact test, and the Mann-Whitney U Test. Nicotine was present in 22 (6.8%) and cotinine in 65 (20.3%) of the 320 samples. The nicotine and cotinine concentrations per sample ranged from 0 to 26.3 ng/ml and 0-363.0 ng/ml, respectively. Benzo[a]pyrene was not detectable in any of the samples analysed. Nicotine and cotinine were also present in the FF of patients with exclusive consumption of e-cigarettes or hookahs. The clinical pregnancy rate, fertilization and maturation rates, and number of oocytes per oocyte pick-up were not statistically significantly different between non-smoking, smoking, or vaping/hookah-smoking patients. Smoking and the accumulation of smoking toxins in the FF have no impact on the outcome of MAR treatments-neither the clinical pregnancy rate, maturation and fertilization rates, nor the number of retrieved oocytes were affected. For the first time, nicotine and cotinine were quantified in the FF of patients exclusively vaping e-cigarettes or smoking hookahs. Since vaping liquids and hookah tobaccos contain potentially harmful substances, other adverse effects cannot be excluded.Trial registration ClinicalTrials.gov Identifier: NCT03414567.


Subject(s)
Cotinine , Electronic Nicotine Delivery Systems , Nicotine , Reproductive Techniques, Assisted , Humans , Female , Adult , Reproductive Techniques, Assisted/adverse effects , Cotinine/analysis , Nicotine/analysis , Nicotine/adverse effects , Prospective Studies , Pregnancy , Follicular Fluid/metabolism , Follicular Fluid/chemistry , Benzo(a)pyrene/analysis , Male , Vaping/adverse effects , Water Pipe Smoking/adverse effects , Smoking/adverse effects
16.
Ecotoxicol Environ Saf ; 276: 116287, 2024 May.
Article in English | MEDLINE | ID: mdl-38579532

ABSTRACT

Benzo(a)pyrene (BaP) can be detected in the human placenta. However, little is known about the effects of BaP exposure on different placental cells under various conditions. In this study, we aimed to investigate the effects of BaP on mitochondrial function, pyrin domain-containing protein 3 (NLRP3) inflammasome, and apoptosis in three human trophoblast cell lines under normoxia, hypoxia, and inflammatory conditions. JEG-3, BeWo, and HTR-8/SVneo cell lines were exposed to BaP under normoxia, hypoxia, or inflammatory conditions for 24 h. After treatment, we evaluated cell viability, apoptosis, aryl hydrocarbon receptor (AhR) protein and cytochrome P450 (CYP) gene expression, mitochondrial function, including mitochondrial DNA copy number (mtDNAcn), mitochondrial membrane potential (ΔΨm), intracellular adenosine triphosphate (iATP), and extracellular ATP (eATP), nitric oxide (NO), NLPR3 inflammasome proteins, and interleukin (IL)-1ß. We found that BaP upregulated the expression of AhR or CYP genes to varying degrees in all three cell lines. Exposure to BaP alone increased ΔΨm in all cell lines but decreased NO in BeWo and HTR-8/SVneo, iATP in HTR-8/SVneo, and cell viability in JEG-3, without affecting apoptosis. Under hypoxic conditions, BaP did not increase the expression of AhR and CYP genes in JEG-3 cells but increased CYP gene expression in two others. Pro-inflammatory conditions did not affect the response of the 3 cell lines to BaP with respect to the expression of CYP genes and changes in the mitochondrial function and NLRP3 inflammasome proteins. In addition, in HTR-8/SVneo cells, BaP increased IL-1ß secretion in the presence of hypoxia and poly(I:C). In conclusion, our results showed that BaP affected mitochondrial function in trophoblast cell lines by increasing ΔΨm. This increased ΔΨm may have rescued the trophoblast cells from activation of the NLRP3 inflammasome and apoptosis after BaP treatment. We also observed that different human trophoblast cell lines had cell type-dependent responses to BaP exposure under normoxia, hypoxia, or pro-inflammatory conditions.


Subject(s)
Apoptosis , Benzo(a)pyrene , Cell Survival , NLR Family, Pyrin Domain-Containing 3 Protein , Placenta , Receptors, Aryl Hydrocarbon , Trophoblasts , Humans , Benzo(a)pyrene/toxicity , Placenta/drug effects , Placenta/cytology , Cell Line , Female , Pregnancy , Apoptosis/drug effects , Trophoblasts/drug effects , Trophoblasts/metabolism , Receptors, Aryl Hydrocarbon/metabolism , Cell Survival/drug effects , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Inflammasomes/drug effects , Inflammasomes/metabolism , Mitochondria/drug effects , Inflammation/chemically induced , Cell Hypoxia/drug effects , Membrane Potential, Mitochondrial/drug effects , Cytochrome P-450 Enzyme System/metabolism , Basic Helix-Loop-Helix Transcription Factors/metabolism , Basic Helix-Loop-Helix Transcription Factors/genetics
17.
Mutat Res ; 828: 111855, 2024.
Article in English | MEDLINE | ID: mdl-38569440

ABSTRACT

Environmental and occupational exposure to polycyclic aromatic hydrocarbons (PAHs) is associated with adverse health effects in humans. Uncertainty exists regarding the causation of urinary bladder cancer by benzo[a]pyrene (B[a]P) due to a lack of sufficient data. In this work, we focused on in-vitro DNA damage and the formation of micronuclei and chromosomal aberrations as predictors of cancer risk, applying a wide range of dosages and time periods to quantify the onset, intensity, and duration of the response. We chose two urothelial cell types to compare susceptibility and the ability to increase the malignity of a pre-existing bladder cancer: a cancer cell line (T24) and a pooled sample of primary urinary bladder epithelia cells (PUBEC) from pigs. The highest level of DNA damage assessed by comet assay was observed following 24-h treatment in both cell types, whereas PUBEC cells were clearly more susceptible. Even 4-h treatment induced DNA damage in PUBEC cells with benchmark doses of 0.0027 µM B[a]P and 0.00023 µM after 4-h and 24-h exposure, respectively. Nearly no effect was observed for periods of 48 h. The frequency of micronucleus formation increased more markedly in T24 cells, particularly with 24-h treatment. In PUBEC cells, 48-h exposure notably induced the formation of nucleoplasmic bridges and nuclear buds. Even though only one biological replicate was studied due to the sophisticated study design, our results give a strong indication of the potential of B[a]P to induce and increase malignity in human-relevant cell types.


Subject(s)
Benzo(a)pyrene , Chromosomal Instability , DNA Damage , Urothelium , Benzo(a)pyrene/toxicity , DNA Damage/drug effects , Pilot Projects , Animals , Urothelium/drug effects , Urothelium/pathology , Chromosomal Instability/drug effects , Humans , Swine , Micronucleus Tests , Dose-Response Relationship, Drug , Chromosome Aberrations , Urinary Bladder Neoplasms/chemically induced , Urinary Bladder Neoplasms/pathology , Urinary Bladder Neoplasms/genetics , Time Factors , Comet Assay , Cell Line, Tumor , Urinary Bladder/drug effects , Urinary Bladder/pathology
18.
World J Microbiol Biotechnol ; 40(6): 180, 2024 Apr 26.
Article in English | MEDLINE | ID: mdl-38668960

ABSTRACT

DNA adduction in the model yeast Saccharomyces cerevisiae was investigated after exposure to the fungicide penconazole and the reference genotoxic compound benzo(a)pyrene, for validating yeasts as a tool for molecular toxicity studies, particularly of environmental pollution. The effect of the toxicants on the yeast's growth kinetics was determined as an indicator of cytotoxicity. Fermentative cultures of S. cerevisiae were exposed to 2 ppm of Penconazole during different phases of growth; while 0.2 and 2 ppm of benzo(a)pyrene were applied to the culture medium before inoculation and on exponential cultures. Exponential respiratory cultures were also exposed to 0.2 ppm of B(a)P for comparison of both metabolisms. Penconazole induced DNA adducts formation in the exponential phase test; DNA adducts showed a peak of 54.93 adducts/109 nucleotides. Benzo(a)pyrene induced the formation of DNA adducts in all the tests carried out; the highest amount of 46.7 adducts/109 nucleotides was obtained in the fermentative cultures after the exponential phase exposure to 0.2 ppm; whereas in the respiratory cultures, 14.6 adducts/109 nucleotides were detected. No cytotoxicity was obtained in any experiment. Our study showed that yeast could be used to analyse DNA adducts as biomarkers of exposure to environmental toxicants.


Subject(s)
Benzo(a)pyrene , DNA Adducts , Environmental Pollutants , Saccharomyces cerevisiae , DNA Adducts/metabolism , Saccharomyces cerevisiae/drug effects , Saccharomyces cerevisiae/metabolism , Saccharomyces cerevisiae/genetics , Saccharomyces cerevisiae/growth & development , Benzo(a)pyrene/toxicity , Benzo(a)pyrene/metabolism , Environmental Pollutants/toxicity , Environmental Pollutants/metabolism , Mutagens/toxicity , Mutagens/metabolism , DNA, Fungal/genetics , Fungicides, Industrial/toxicity , Fungicides, Industrial/metabolism
19.
Environ Sci Technol ; 58(19): 8565-8575, 2024 May 14.
Article in English | MEDLINE | ID: mdl-38575864

ABSTRACT

Benzo[a]pyrene is difficult to remove from soil due to its high octanol/water partition coefficient. The use of mixed surfactants can increase solubility but with the risk of secondary soil contamination, and the compounding mechanism is still unclear. This study introduced a new approach using environmentally friendly fatty acid methyl ester sulfonate (MES) and alkyl polyglucoside (APG) to solubilize benzo[a]pyrene. The best result was obtained when the ratio of MES/APG was 7:1 under 6 g/L total concentration, with an apparent solubility (Sw) of 8.58 mg/L and a molar solubilization ratio (MSR) of 1.31 for benzo[a]pyrene, which is comparable to that of Tween 80 (MSR, 0.95). The mechanism indicates that the hydroxyl groups (-OH) in APG form "O-H···OSO2-" hydrogen bonding with the sulfonic acid group (-SO3-) of MES, which reduces the electrostatic repulsion between MES molecules, thus facilitating the formation of large and stable micelles. Moreover, the strong solubilizing effect on benzo[a]pyrene should be ascribed to the low polarity of ester groups (-COOCH3) in MES. Functional groups capable of forming hydrogen bonds and having low polarity are responsible for the enhanced solubilization of benzo[a]pyrene. This understanding helps choose suitable surfactants for the remediation of PAH-contaminated soils.


Subject(s)
Benzo(a)pyrene , Solubility , Surface-Active Agents , Surface-Active Agents/chemistry , Benzo(a)pyrene/chemistry , Soil Pollutants/chemistry
20.
Immunol Lett ; 267: 106858, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38631465

ABSTRACT

The function of CD5 protein in T cells is well documented, but regulation of its surface-level expression has yet to be fully understood. However, variation in its surface expression is associated with various immunopathological conditions and haematological malignancies. Briefly, expression of an alternate exon E1B of a human endogenous retroviruses (HERV) origin directly downregulates the conventional transcript variant (E1A), as its expression leads to the retention of the resultant protein at the intracellular level (cCD5). A separate promoter governs the expression of E1B and may be influenced by different transcription factors. Hence, we performed in silico transcription factor binding site (TFBS) analysis of the 3 kb upstream region from TSS of exon E1B and found five putative DREs (Dioxin Response elements) with good similarity scores. Further, we observed the upregulation in E1B expression after the exposure of BaP (a dioxin) and the reduction of E1A expression and their respective protein, i.e. sCD5 and cCD5. The binding of AHR at the predicted DRE sites was confirmed by ChIP qPCR and AHR specific inhibitor and gene silencing studies suggested the involvement of AHR in exonal switch. This study indicates that the polycyclic aromatic hydrocarbon decreases the sCD5 expression by upregulating alternative exon expression, which may adversely affect the overall T cell functions.


Subject(s)
Benzo(a)pyrene , CD5 Antigens , Exons , Gene Expression Regulation , Receptors, Aryl Hydrocarbon , Humans , CD5 Antigens/metabolism , CD5 Antigens/genetics , Receptors, Aryl Hydrocarbon/metabolism , Receptors, Aryl Hydrocarbon/genetics , Exons/genetics , T-Lymphocytes/immunology , T-Lymphocytes/metabolism , Promoter Regions, Genetic/genetics , Basic Helix-Loop-Helix Transcription Factors/metabolism , Basic Helix-Loop-Helix Transcription Factors/genetics , Protein Binding , Endogenous Retroviruses/genetics , Endogenous Retroviruses/metabolism , Binding Sites , Jurkat Cells
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