RESUMEN

c-MYC is one of the most important oncogenes, which is overexpressed in many cancers, and is highly related to development, metastasis, and drug resistance of cancers. The G4 structure in the promoter of c-MYC oncogene contributes a lot to the gene transcriptional mechanism. Small-molecule ligands binding to the c-MYC G4 appear to be a new class of anticancer agents. However, selective ligands for the c-MYC G4 over other G4s have been rarely reported. In this study, we reported a novel fluorescent ligand by migrating the benzene group on a carbazole-benzothiazolium scaffold, which was demonstrated to exhibit considerable specificity to the c-MYC G4, which was distinguished from other small-molecule ligands. The further cellular experiments suggested that this ligand may indeed target the promoter G4 and cause apparent transcriptional inhibition of the c-MYC oncogene instead of other G4-mediated oncogenes, which thereby resulted in cancer cell growth inhibition. Collectively, this study provided a good example for developing specific c-MYC G4 ligands, which may further develop into an effective anticancer agent that inhibit the c-MYC expression.

Asunto(s)

Antineoplásicos , Benzotiazoles , Carbazoles , Proliferación Celular , Colorantes Fluorescentes , G-Cuádruplex , Proteínas Proto-Oncogénicas c-myc , Carbazoles/química , Carbazoles/farmacología , G-Cuádruplex/efectos de los fármacos , Humanos , Ligandos , Benzotiazoles/química , Benzotiazoles/farmacología , Proteínas Proto-Oncogénicas c-myc/metabolismo , Proteínas Proto-Oncogénicas c-myc/antagonistas & inhibidores , Proteínas Proto-Oncogénicas c-myc/genética , Colorantes Fluorescentes/química , Colorantes Fluorescentes/síntesis química , Colorantes Fluorescentes/farmacología , Estructura Molecular , Antineoplásicos/farmacología , Antineoplásicos/química , Antineoplásicos/síntesis química , Proliferación Celular/efectos de los fármacos , Relación Estructura-Actividad , Ensayos de Selección de Medicamentos Antitumorales , Relación Dosis-Respuesta a Droga , Benceno/química , Benceno/farmacología , Línea Celular Tumoral

RESUMEN

In-situ chemical oxidation with persulfate (PS-ISCO) is a preferred approach for the remediation of fuel-contaminated groundwater. Persulfate (PS) can be activated by various methods to produce stronger sulfate radicals for more efficient ISCO. Despite karst aquifers being widespread, there are few reports on PS-ISCO combined with Fe2+-activated PS. To better understand the effects of Fe2+-activated PS for the remediation of gasoline-contaminated aquifers in karst areas, a box-column experiment was conducted under flow conditions, using karst groundwater and limestone particles to simulate an aquifer. Gasoline was used as the source of hydrocarbon contaminants. Dissolved oxygen and nitrate were added to enhance bioremediation (EBR) and ferrous sulfate was used to activate PS. The effect of Fe2+-activated PS combined with biodegradation was compared during the periods of EBR + ISCO and ISCO alone, using the mass flow method for data analysis. The results showed that the initial dissolution of benzene, toluene, and xylene (BTX) from gasoline injection was rapid and variable, with a decaying trend at an average pseudo-first-order degradation rate constant of 0.032 d-1. Enhanced aerobic biodegradation and denitrification played a significant role in limestone-filled environments, with dissolved oxygen and nitrate utilization ratios of 59 ~ 72% and 12-70%, respectively. The efficiency of EBR + ISCO was the best method for BTX removal, compared with EBR or ISCO alone. The pseudo-first-order degradation rate constants of BTX reached 0.022-0.039, 0.034-0.070, and 0.027-0.036 d-1, during the periods of EBR alone, EBR + ISCO, and ISCO alone, respectively. The EBR + ISCO had a higher BTX removal ratio range of 71.0 ~ 84.3% than the ISCO alone with 30.1 ~ 45.1%. The presence of Fe2+-activated PS could increase the degradation rate of BTX with a range of 0.060 ~ 0.070 d-1, otherwise, with a range of 0.034-0.052 d-1. However, Fe2+-activated PS also consumed about 3 times the mass of PS, caused a further decrease in pH with a range of 6.8-7.6, increased 3-4 times the Ca2+ and 1.6-1.8 times the HCO3- levels, and decreased the BTX removal ratio of ISCO + EBR, compared to the case without Fe2+ activation. In addition, the accumulation of ferric hydroxides within a short distance indicated that the range of PS activated by Fe2+ may be limited. Based on this study, it is suggested that the effect of Fe2+-activated PS should be evaluated in the remediation of non-carbonate rock aquifers.

Asunto(s)

Biodegradación Ambiental , Gasolina , Agua Subterránea , Contaminantes Químicos del Agua , Agua Subterránea/química , Contaminantes Químicos del Agua/química , Sulfatos/química , Benceno , Tolueno/química , Hierro/química , Xilenos/química

RESUMEN

The benzene dimer (BD) is an archetypal model of π∙∙∙π and C-H∙∙∙π noncovalent interactions as they occur in its cofacial and perpendicular arrangements, respectively. The enthalpic stabilization of the related BD structures has been debated for a long time and is revisited here. The revisit is based on results of computations that apply the coupled-cluster theory with singles, doubles and perturbative triples [CCSD(T)] together with large basis sets and extrapolate results to the complete basis set (CBS) limit in order to accurately characterize the three most important stationary points of the intermolecular interaction energy (ΔE) surface of the BD, which correspond to the tilted T-shaped (TT), fully symmetric T-shaped (FT) and slipped-parallel (SP) structures. In the optimal geometries obtained by searching extensive sets of the CCSD(T)/CBS ΔE data of the TT, FT and SP arrangements, the resulting ΔE values were -11.84, -11.34 and -11.21 kJ/mol, respectively. The intrinsic strength of the intermolecular bonding in these configurations was evaluated by analyzing the distance dependence of the CCSD(T)/CBS ΔE data over wide ranges of intermonomer separations. In this way, regions of the relative distances that favor BD structures with either π∙∙∙π or C-H∙∙∙π interactions were found and discussed in a broader context.

Asunto(s)

Benceno , Dimerización , Benceno/química , Termodinámica , Modelos Moleculares , Teoría Cuántica , Enlace de Hidrógeno

RESUMEN

A 14-day rat study with plasma metabolomics was conducted to evaluate the toxicity of Benzene. Wistar rats were orally administered Benzene daily at doses of 0, 300 and 1000 mg/kg bw. The study identified liver and kidneys as target organs of Benzene toxicity and found reductions in total white blood cells, absolute lymphocyte and eosinophil cell counts, and increased relative monocyte counts suggesting bone marrow as a target organ. The study also confirmed liver as a target organ using metabolomics, which showed indications of a stress reaction in rats and changes in metabolites suggestive of a metabolic disorder. The metabolomics investigations did not find any other toxicologically relevant modes of action, and the observed metabolite changes were not associated with markers for mitochondrial dysfunction. The study concludes that integration of omics technologies, such as metabolomics, in regulatory toxicity studies is possible, confirms existing knowledge and adds additional information that can be used for mechanistic understanding of observed toxicity.

Asunto(s)

Benceno , Riñón , Hígado , Metaboloma , Metabolómica , Ratas Wistar , Animales , Benceno/toxicidad , Masculino , Metaboloma/efectos de los fármacos , Hígado/efectos de los fármacos , Hígado/metabolismo , Riñón/efectos de los fármacos , Riñón/metabolismo , Riñón/patología , Ratas , Relación Dosis-Respuesta a Droga , Administración Oral

RESUMEN

According to the International Agency for Research on Cancer, leukemia ranks 14th in incidence and 11th in mortality and has a 5-year prevalence of approximately 1300,000 cases. Acute lymphoblastic leukemia is the most common hematopoietic syndrome in children during the first 5 years of life and represents approximately 75 % of all neoplasms among the pediatric population. The development of leukemia is strongly governed by DNA alterations that accelerate the growth of bone marrow cells. Currently, the most examined factor in pediatric leukemia is exposure to multiple compounds, such as hydrocarbons. Benzene, an aromatic hydrocarbon, can cause health challenges and is categorized as a carcinogen. Benzene toxicity has been widely associated with occupational exposure. Importantly, studies are underway to generate evidence that can provide clues regarding the risk of environmental benzene exposure and hematological problems in children. In this review, we summarize the existing evidence regarding the effects of benzene on pediatric leukemia, the associations between the effect of benzene on carcinogenesis, and the presence of certain molecular signatures in benzene-associated pediatric leukemia. Although there is sufficient evidence regarding the effects of benzene on carcinogenesis and leukemia, epidemiological research has primarily focused on occupational risk. Moreover, most benzene-induced molecular and cytogenetic alterations have been widely described in adults but not in the pediatric population. Thus, epidemiological efforts are crucial in the pediatric population in terms of epidemiological, clinical, and biomedical research.

Asunto(s)

Benceno , Exposición a Riesgos Ambientales , Humanos , Benceno/toxicidad , Niño , Exposición a Riesgos Ambientales/efectos adversos , Leucemia/inducido químicamente , Leucemia/epidemiología , Leucemia/genética , Exposición Profesional/efectos adversos , Preescolar , Leucemia-Linfoma Linfoblástico de Células Precursoras/epidemiología , Leucemia-Linfoma Linfoblástico de Células Precursoras/inducido químicamente , Factores de Riesgo , Lactante

RESUMEN

The associations between blood benzene, toluene, ethylbenzene, and xylenes (BTEX) and biological aging among general adults remain elusive. The present study comprised 5780 participants from the National Health and Nutrition Examination Survey 1999-2010. A novel measure of biological aging, phenotypic age acceleration (PhenoAge.Accel), derived from biochemical markers was calculated. Weighted generalized linear regression and weighted quantile sum regression (WQS) were utilized to assess the associations between BTEX components and mixed exposure, and PhenoAge.Accel. The mediating roles of systemic immune-inflammation index (SII) and oxidative stress indicators (serum bilirubin and gamma-glutamyl transferase), along with the modifying effects of body mass index (BMI) were also examined. In the single-exposure model, the highest quantile of blood benzene (b = 0.89, 95%CI: 0.58 to 1.20), toluene (b = 0.87, 95%CI: 0.52 to 1.20), and ethylbenzene (b = 0.80, 95%CI: 0.46 to 1.10) was positively associated with PhenoAge.Accel compared to quantile 1. Mixed-exposure analyses revealed a consistent positive association between BTEX mixed exposure and PhenoAge.Accel (b = 0.88, 95%CI: 0.56 to 1.20), primarily driven by benzene (92.78%). The association between BTEX and PhenoAge.Accel was found to be partially mediated by inflammation and oxidative stress indicators (ranging from 3.2% to 13.7%). Additionally, BMI negatively modified the association between BTEX mixed exposure and PhenoAge.Accel, with a threshold identified at 36.2 kg/m^2. Furthermore, BMI negatively moderated the direct effect of BTEX mixed exposure on PhenoAge.Accel in moderated mediation models, while positively modified the link between SII and PhenoAge.Accel in the indirect path (binteraction = 0.04, 95%CI: 0.01 to 0.06). Overall, BTEX mixed exposure was associated with PhenoAge.Accel among US adults, with benzene may have reported most contribution, and inflammation and oxidative damage processes may partially explain this underlying mechanism. The study also highlighted the potential benefits of appropriate BMI increased. Additional large-scale cohort studies and experiments were necessary to substantiate these findings.

Asunto(s)

Derivados del Benceno , Benceno , Índice de Masa Corporal , Exposición a Riesgos Ambientales , Inflamación , Estrés Oxidativo , Tolueno , Xilenos , Humanos , Tolueno/sangre , Inflamación/sangre , Masculino , Persona de Mediana Edad , Femenino , Adulto , Exposición a Riesgos Ambientales/estadística & datos numéricos , Envejecimiento , Anciano , Encuestas Nutricionales

RESUMEN

Benzene is a common contaminant in the workplace and wider environment, which induces hematotoxicity. Our previous study has implicated that lncRNAs mediated apoptosis and autophagy induced by benzene. Nevertheless, the roles of extracellular vesicle(EVs)-derived lncRNAs in benzene toxicity are unknown. However, the role of EVs and EVs-derived lncRNAs in benzene-induced toxicity remains unclear. In this research, we explored the function of EVs and EVs-derived lncRNAs in cell-cell communication through benzene-induced apoptosis and autophagy. Our findings demonstrated that EVs derived from 1,4-BQ-treated cells treated cells and coculture with 1,4-BQ-treated cells enhanced apoptosis and autophagy via regulating the pathways of PI3K-AKT-mTOR and chaperone-mediated autophagy. Treating with GW4869 in 1,4-BQ-treated cells significantly inhibited EV secretion, which reduced apoptosis and autophagy. Furthermore, we identified a set of differentially expressed autophagy- and apoptosis-related lncRNAs using EVs-derived lncRNA sequencing. Among them, 8 candidate lncRNAs were upregulated in EVs derived from 1,4-BQ-treated cells, as determined by lncRNA sequencing and qRT-PCR. Importantly, these lncRNAs were also increased in the serum EVs of benzene-exposed workers. 1,4-BQ-treated cells released EVs that transfer differentially expressed lncRNAs, thereby inducing apoptosis and autophagy in the recipient cells. The above results support the hypothesis that EVs-derived lncRNAs participate in intercellular communication during benzene-induced hematotoxicity and function as potential biomarkers for risk assessment of benzene-exposed workers.

Asunto(s)

Apoptosis , Autofagia , Benceno , Vesículas Extracelulares , ARN Largo no Codificante , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Autofagia/efectos de los fármacos , Humanos , Apoptosis/efectos de los fármacos , Vesículas Extracelulares/efectos de los fármacos , Vesículas Extracelulares/metabolismo , Benceno/toxicidad , Exposición Profesional/efectos adversos , Masculino , Transducción de Señal/efectos de los fármacos

Asunto(s)

Benceno , Peróxido de Benzoílo , Humanos , Benceno/efectos adversos , Peróxido de Benzoílo/administración & dosificación , Fármacos Dermatológicos/administración & dosificación , Fármacos Dermatológicos/efectos adversos

RESUMEN

The ubiquitous use of mosquito repellents in homes across Asia, Africa, and South America is related with human exposure to indoor volatile organic compounds (VOCs). There are three primary types of mosquito repellents: those in the form of coils, mats, and liquids. The repellent mechanisms of these products are distinct, resulting in the generation of varying types of VOCs during the repellent process. In this study, the emission characteristics of commercial coil-, mat-, and liquid-type mosquito repellents were observed in a laboratory chamber using real-time measurement. A previously developed personal passive sampler, ePTFE PS, was used to quantify personal exposure to indoor VOCs while 86 volunteers habitually used those three representative types for 3 h in their residence. Notable increase of indoor benzene was observed for coil- and mat-type mosquito repellents, while α-pinene concentration increased significantly following the use of liquid-type mosquito repellent. The average incremental cancer risks for benzene were 10-6 to 10-4 for adults following the use of coil- and mat-type mosquito repellents. The average non-cancer risks for all chemicals were <1 after the use of three types of mosquito repellents. Considering the potential human health risks associated with byproducts (e.g., particulate matter or carbon monoxide from incomplete combustion) emitted after mosquito coil use, further research on this topic is warranted.

Asunto(s)

Contaminación del Aire Interior , Repelentes de Insectos , Compuestos Orgánicos Volátiles , Repelentes de Insectos/análisis , Compuestos Orgánicos Volátiles/análisis , Humanos , Contaminación del Aire Interior/análisis , Contaminación del Aire Interior/estadística & datos numéricos , Monitoreo del Ambiente/métodos , Contaminantes Atmosféricos/análisis , Vivienda , Exposición a Riesgos Ambientales/análisis , Exposición a Riesgos Ambientales/estadística & datos numéricos , Medición de Riesgo , Adulto , Benceno/análisis , Culicidae/efectos de los fármacos

RESUMEN

Cancer has been an enormous pain point for patients and regulatory bodies across the globe. In Dec. 2023, the US FDA released guidance on benzene-grade carbomer formulations, which triggered pharmaceutical manufacturers to assess risk, test finished products, and reformulate drug products with benzene-grade carbomer. The immediate implementation of the stoppage of finished products with benzene-grade carbomers has threatened pharmaceutical excipients and finished product manufacturers. The gravity of this situation prompted the US Pharmacopeia to extend the deadline for discontinuation from August 1, 2025, to August 1, 2026, allowing manufacturers ample time for reformulation and regulatory compliance.There is an immediate need to understand the guidance and to learn how manufacturers should do the risk assessment and approach reformulation. This review provides an in-depth analysis of the risk assessment and reformulation processes involved in various dosage forms utilizing benzene-grade carbomer, supported by specific case studies.This review offers insights into navigating the USFDA guidelines to ensure formulation safety and compliance, thus enabling pharmaceutical practitioners to uphold the highest standards of patient care and tackle life cycle management challenges.The decision of the USFDA to restrict the usage of high benzene content of carbomer in the formulation is a welcome move. This article has shown a way for researchers to see opportunities in the path and provide best-in-class medicines to patients with a better formulation safety profile.

Asunto(s)

Benceno , United States Food and Drug Administration , Medición de Riesgo/métodos , Estados Unidos , Benceno/química , United States Food and Drug Administration/normas , Humanos , Química Farmacéutica/métodos , Excipientes/química , Composición de Medicamentos/métodos , Industria Farmacéutica/métodos , Industria Farmacéutica/normas , Resinas Acrílicas/química

RESUMEN

A Pt nanoparticle-immobilized WO3 material is a promising candidate for catalytic reactions, and the surface and electronic structure can strongly affect the performance. However, the effect of the intrinsic oxygen vacancy of WO3 on the d-band structure of Pt and the synergistic effect of Pt and the WO3 matrix on reaction performance are still ambiguous, which greatly hinders the design of advanced materials. Herein, Pt-decorated WO3 nanosheets with different electronic metal-support interactions are successfully prepared by finely tuning the oxygen vacancy structure of WO3 nanosheets. Notably, Pt-modified WO3 nanosheets annealed at 400 °C exhibit excellent benzene series (BTEX) sensing performance (S = 377.33, 365.21, 348.45, and 319.23 for 50 ppm ethylbenzene, benzene, toluene, and xylene, respectively, at 140 °C), fast response and recovery dynamics (10/7 s), excellent reliability (σ = 0.14), and sensing stability (φ = 0.08%). Detailed structural characterization and DFT results reveal that interfacial Ptδ+-Ov-W5+ sites are recognized as the active sites, and the oxygen vacancies of the WO3 matrix can significantly affect the d-band structure of Pt nanoparticles. Notably, Pt/WO3-400 with improved surface oxygen mobility and medium electronic metal-support interaction facilitates the activation and desorption of BTEX, which contributes to the highly efficient BTEX sensing performance. Our work provides a new insight for the design of high-performance surface reaction materials for advanced applications.

Asunto(s)

Derivados del Benceno , Benceno , Óxidos , Oxígeno , Platino (Metal) , Tungsteno , Tungsteno/química , Platino (Metal)/química , Óxidos/química , Oxígeno/química , Benceno/química , Derivados del Benceno/química , Nanoestructuras/química , Xilenos/química , Nanopartículas del Metal/química , Tolueno/química , Técnicas Electroquímicas/métodos , Teoría Funcional de la Densidad

RESUMEN

Initial volatile concentration (Cs0) is a crucial parameter for the migration and diffusion of volatile organic pollutants (VOCs) from the soil to the atmosphere. The acquisition of Cs0 is, however, time-consuming and labor-intensive. This study developed a prediction model for Cs0 based on theoretical analysis and experimental simulations. The model was established by correlating the molecular kinetic and sorption potential energy. The pore structure and pore size distribution of the soil were analyzed based on the fractal theory of porous media, followed by calculating the sorption potential energy corresponding to each pore size. It was observed that the pore size distribution of soil influenced BTEX (benzene, toluene, ethylbenzene, and xylene) volatilization by impacting sorption potential energy. The soil parameters, such as organic matter and soil moisture content, and the initial concentration and physical properties of BTEX were coupled to the prediction model to ensure its practicability. Red soil was finally used to verify the accuracy and applicability of the model. The experimental and predicted values' maximum relative and root-mean-square errors were determined to be 24.2% and 11.7%, respectively. The model provides a simple, rapid, and accurate assessment of soil vapor emission content due to BTEX contamination. This study offers an economical and practical method for quantifying the amount of volatile BTEX in contaminated sites, providing a reference for its monitoring, control, and subsequent remediation.

Asunto(s)

Derivados del Benceno , Benceno , Contaminantes del Suelo , Suelo , Tolueno , Compuestos Orgánicos Volátiles , Xilenos , Contaminantes del Suelo/análisis , Contaminantes del Suelo/química , Compuestos Orgánicos Volátiles/análisis , Compuestos Orgánicos Volátiles/química , Tolueno/química , Tolueno/análisis , Volatilización , Benceno/química , Benceno/análisis , Derivados del Benceno/química , Derivados del Benceno/análisis , Suelo/química , Xilenos/química , Xilenos/análisis , Adsorción , Modelos Químicos , Monitoreo del Ambiente/métodos

RESUMEN

Benzene is a common environmental pollutant and significant health hazard. Low-dose benzene exposure is common in most industrial settings, and some workers exhibit hematotoxicity characterized by impaired hematopoietic function. Consequently, understanding the early hematopoietic damage and biomarkers associated with low-dose benzene exposure is of critical importance for health risk assessment. Using data from a 5-year prospective cohort study on benzene exposure and the National Center for Biotechnology Information's Gene Expression Omnibus database, we detected significant downregulation of the ubiquitin-conjugating enzyme UBE2L3 (E2) in benzene-exposed subjects compared to control subjects. Liquid chromatography tandem mass spectrometry and co-immunoprecipitation experiments illustrated the binding interaction between UBE2L3 and the ubiquitin-protein ligase ZNF598 (E3). We applied deep learning algorithms to predict candidate interacting proteins and then conducted validation via co-immunoprecipitation experiments, which showed that ZNF598 engages in binding with the autophagy protein LAMP-2. Subsequent overexpression and knockdown of UBE2L3 coupled with immunofluorescence experiments and transmission electron microscopy revealed that UBE2L3 disrupts the ubiquitination-degradation of LAMP-2 by ZNF598, reduces GPX4 expression levels, and activates an autophagy-dependent ferroptosis pathway. It also leads to increased lipid peroxidation, thereby promoting ferroptosis and contributing to the hematotoxicity induced by benzene. In summary, our results suggest that UBE2L3 may be involved in early hematopoietic damage by modulating the autophagy-dependent ferroptosis signaling pathway in benzene-induced hematotoxicity.

Asunto(s)

Autofagia , Benceno , Ferroptosis , Enzimas Ubiquitina-Conjugadoras , Ferroptosis/efectos de los fármacos , Enzimas Ubiquitina-Conjugadoras/metabolismo , Enzimas Ubiquitina-Conjugadoras/genética , Benceno/toxicidad , Autofagia/efectos de los fármacos , Humanos , Contaminantes Ambientales/toxicidad , Estudios Prospectivos , Masculino , Adulto , Femenino

RESUMEN

Neuromuscular signal transmission is affected in various diseases including myasthenia gravis, congenital myasthenic syndromes, and sarcopenia. We used an ATF2-luciferase system to monitor the phosphorylation of MuSK in HEK293 cells introduced with MUSK and LRP4 cDNAs to find novel chemical compounds that enhanced agrin-mediated acetylcholine receptor (AChR) clustering. Four compounds with similar chemical structures carrying benzene rings and heterocyclic rings increased the luciferase activities 8- to 30-folds, and two of them showed continuously graded dose dependence. The effects were higher than that of disulfiram, a clinically available aldehyde dehydrogenase inhibitor, which we identified to be the most competent preapproved drug to enhance ATF2-luciferase activity in the same assay system. In C2C12 myotubes, all the compounds increased the area, intensity, length, and number of AChR clusters. Three of the four compounds increased the phosphorylation of MuSK, but not of Dok7, JNK. ERK, or p38. Monitoring cell toxicity using the neurite elongation of NSC34 neuronal cells as a surrogate marker showed that all the compounds had no effects on the neurite elongation up to 1 µM. Extensive docking simulation and binding structure prediction of the four compounds with all available human proteins using AutoDock Vina and DiffDock showed that the four compounds were unlikely to directly bind to MuSK or Dok7, and the exact target remained unknown. The identified compounds are expected to serve as a seed to develop a novel therapeutic agent to treat defective NMJ signal transmission.

Asunto(s)

Fibras Musculares Esqueléticas , Receptores Nicotínicos , Receptores Nicotínicos/genética , Receptores Nicotínicos/metabolismo , Fibras Musculares Esqueléticas/efectos de los fármacos , Fibras Musculares Esqueléticas/metabolismo , Animales , Ratones , Línea Celular , Humanos , Factor de Transcripción Activador 2/genética , Factor de Transcripción Activador 2/metabolismo , Genes Reporteros , Proteínas Relacionadas con Receptor de LDL/genética , Proteínas Relacionadas con Receptor de LDL/metabolismo , Proteínas Tirosina Quinasas Receptoras/genética , Proteínas Tirosina Quinasas Receptoras/metabolismo , Receptores Colinérgicos/genética , Receptores Colinérgicos/metabolismo , Familia de Multigenes , Transducción de Señal/efectos de los fármacos , Proteínas Musculares/genética , Proteínas Musculares/metabolismo , Neuritas , Bungarotoxinas/farmacología , Benceno/farmacología , Compuestos Heterocíclicos/farmacología , Simulación del Acoplamiento Molecular

RESUMEN

BACKGROUND: Oil refinery workers are exposed to benzene, which is a well-known cause of leukaemia, but results on leukaemia in oil refinery workers have been mixed, and the data on workers' exposure is limited. Oil refinery workers are also exposed to asbestos and several studies have shown increased risk of mesothelioma. AIM: The objective was to investigate cancer incidence, especially leukaemia, at low to moderate exposure to benzene in an update of a previous study of employees at three Swedish oil refineries. METHODS: Cancer incidence was followed up in 2264 men (1548 refinery operators) employed at three oil refineries in Sweden for at least one year. Job types and employment times were collected from complete company files. A retrospective assessment of the benzene exposure was performed by occupational hygienists in collaboration with the refineries using historic measurements as well as detailed information on changes in the industrial hygiene and technological developments. Cases of cancer were retrieved by a linkage with the Swedish Cancer Register through 35-47 years of follow-up and standardized incidence ratios (SIR) with 95% confidence intervals (CI) were calculated. RESULTS: In total, 258 tumors had occurred versus 240 expected (SIR 1.07; 95% CI 0.95-1.21). There were 10 cases of leukaemia, all in refinery operators (SIR 2.4; 95% CI 1.18-4.51). There were three cases of pleural mesothelioma, two of which in refinery operators. The mean estimated cumulative benzene exposure for the cases of leukaemia was 7.9 ppm-years (median 4.9, range 0.1-31.1). DISCUSSION: The study suggests that low to moderate average cumulative benzene exposure increases the risk of leukaemia. Limitations include the modest number of cases and potential misclassification of exposure. CONCLUSION: The present study indicated an increased risk of leukaemia in male oil refinery workers with low to moderate exposure to benzene.

Asunto(s)

Benceno , Leucemia , Exposición Profesional , Industria del Petróleo y Gas , Humanos , Benceno/toxicidad , Suecia/epidemiología , Exposición Profesional/efectos adversos , Masculino , Incidencia , Persona de Mediana Edad , Adulto , Leucemia/epidemiología , Leucemia/inducido químicamente , Enfermedades Profesionales/epidemiología , Enfermedades Profesionales/inducido químicamente , Estudios Retrospectivos , Neoplasias/epidemiología , Neoplasias/inducido químicamente , Contaminantes Ocupacionales del Aire

RESUMEN

This study aims to identify sources of groundwater contamination in a refinery area using integrated compound-specific stable isotope analysis (CSIA), oil fingerprinting techniques, hydrogeological data, and distillation analysis. The investigations focused on determination of the origin of benzene, toluene, ethylbenzene, and xylenes (BTEX), and aliphatic hydrocarbons as well. Groundwater and floating oil samples were collected from extraction wells for analysis. Results indicate presence of active leaks in both the northern and southern zones. In the northern zone, toluene was found to primarily originate from oil products like aviation turbine kerosene (ATK or aviation fuel), kerosene, regular gasoline, and diesel fuel. Additionally, stable isotope ratios of carbon and hydrogen for ethylbenzene, o-xylene (ortho xylene) and p-xylene (para xylene) in zone A suggested the pollution originated from gasoline within the northern zone. The origin of super gasoline (with higher octane) identified in southern zone using δ13C and δ2H values of toluene in the floating oil and groundwater samples. Further, biodegradation of toluene likely occurred in southern zone according to δ13C and δ2H. The findings underscore the critical importance of integrating CSIA and fingerprinting techniques to effectively address the challenges of source identification and relying solely on each method independently is insufficient. Accordingly, comparing the GC-MS results of floating oil samples with ATK and jet fuel (JP4) standards can be effectively utilized for source differentiation. However, this method showed no practical application to distinguish different types of diesel or gasoline. The accuracy and reliability of source identification of BTEX compounds may significantly improve when hydrogeological data incorporates with stable isotopes analysis. Additionally, the results of this study will elevate the procedures for fuel-related contaminants source identification of the polluted groundwater that is crucial to develop effective remediation strategies.

Asunto(s)

Benceno , Agua Subterránea , Tolueno , Contaminantes Químicos del Agua , Xilenos , Agua Subterránea/química , Xilenos/análisis , Benceno/análisis , Tolueno/análisis , Contaminantes Químicos del Agua/análisis , Monitoreo del Ambiente , Derivados del Benceno/análisis

RESUMEN

Benzene is associated with diverse occupational and public health hazards. It exhibits an ability to rapidly permeate the skin and contaminate water and food sources, leading to dermal and ingestion exposures. Despite numerous studies examining the associations between benzene and various indicators of harm, the findings have yielded inconsistent results. Furthermore, relying solely on air concentration as a measure of benzene exposure is limited, as it fails to account for internal exposure dose and individual susceptibility. This study aimed to conduct a comprehensive review in order to present current knowledge on benzene biomarkers and their significance in evaluating exposure levels and associated health hazards. The search methodology adhered to the PRISMA guidelines and involved the application of specific inclusion and exclusion criteria across multiple databases including PubMed, Embase, and Web of Science. Two researchers independently extracted and evaluated the relevant data based on predetermined criteria. Following the screening process, a total of 80 articles were considered eligible out of the initially retrieved 1053 articles after undergoing screening and assessment for inclusion. As the level of exposure decreased, specific biomarkers demonstrated a gradual increase in limitations, including heightened background concentrations and vulnerability to confounding factors. The advancement of sampling and analysis techniques will yield new biomarkers. Additionally, when conducting practical work, it is crucial to employ a comprehensive utilization of diverse biomarkers while excluding individual metabolic variations and combined exposure factors.

Asunto(s)

Benceno , Biomarcadores , Exposición Profesional , Benceno/análisis , Benceno/toxicidad , Humanos , Exposición Profesional/análisis , Exposición Profesional/efectos adversos , Biomarcadores/análisis

RESUMEN

Benzene is a common environmental and occupational pollutant, benzene exposure causes damage to hematopoietic system. ZMAT3 is a zinc finger protein which has important biological functions. In this study, benzene-exposed mouse model and ZMAT3 overexpression and low expression hematopoietic stem cells (HSCs) models were constructed to explore the mechanism of ZMAT3 in benzene-induced hematopoietic toxicity. The results showed that benzene increased the expression of ZMAT3 in mouse bone marrow (BM) cells, HSCs and peripheral blood (PB) leukocyte, and the changes in HSCs were more sensitive than BM and PB cells. In addition, overexpression of ZMAT3 decreased the self-renewal ability of HSCs and reduced the HSCs differentiation into myeloid hematopoietic cells, while low expression has the opposite effect. Besides, over and low expression of ZMAT3 both increased the HSCs differentiation into lymphoid progenitor cells. Moreover, bioinformatics analysis suggested that ZMAT3 was associated with TNF-α signaling pathway, and the correlation was confirmed in mouse model. Meanwhile, the results indicated that ZMAT3 promoted TNF-α mRNA processing by binding to the ARE structural domain on TNF-α and interacting with hnRNP A2/B1 and hnRNP A1 proteins, ultimately activating the NF-κB signaling pathway. This study provides a new mechanism for the study of benzene toxicity.

Asunto(s)

Benceno , Diferenciación Celular , Células Madre Hematopoyéticas , FN-kappa B , Transducción de Señal , Factor de Necrosis Tumoral alfa , Animales , Células Madre Hematopoyéticas/efectos de los fármacos , Células Madre Hematopoyéticas/metabolismo , Benceno/toxicidad , FN-kappa B/metabolismo , FN-kappa B/genética , Diferenciación Celular/efectos de los fármacos , Factor de Necrosis Tumoral alfa/metabolismo , Factor de Necrosis Tumoral alfa/genética , Ratones , Transducción de Señal/efectos de los fármacos , Masculino , Ratones Endogámicos C57BL , Autorrenovación de las Células/efectos de los fármacos

RESUMEN

Background: Conventional biofilters, which rely on bacterial activity, face challenges in eliminating hydrophobic compounds, such as aromatic compounds. This is due to the low solubility of these compounds in water, which makes them difficult to absorb by bacterial biofilms. Furthermore, biofilter operational stability is often hampered by acidification and drying out of the filter bed. Methods: Two bioreactors, a bacterial biofilter (B-BF) and a fungal-bacterial coupled biofilter (F&B-BF) were inoculated with activated sludge from the secondary sedimentation tank of the Sinopec Yangzi Petrochemical Company wastewater treatment plant located in Nanjing, China. For approximately 6 months of operation, a F&B-BF was more effective than a B-BF in eliminating a gas-phase mixture containing benzene, toluene, ethylbenzene, and para-xylene (BTEp-X). Results: After operating for four months, the F&B-BF showed higher removal efficiencies for toluene (T), ethylbenzene (E), benzene (B), and para-X (p-Xylene), at 96.9%, 92.6%, 83.9%, and 83.8%, respectively, compared to those of the B-BF (90.1%, 78.7%, 64.8%, and 59.3%). The degradation activity order for B-BF and F&B-BF was T > E > B > p-X. Similarly, the rates of mineralization for BTEp-X in the F&B-BF were 74.9%, 66.5%, 55.3%, and 45.1%, respectively, which were higher than those in the B-BF (56.5%, 50.8%, 43.8%, and 30.5%). Additionally, the F&B-BF (2 days) exhibited faster recovery rates than the B-BF (5 days). Conclusions: It was found that a starvation protocol was beneficial for the stable operation of both the B-BF and F&B-BF. Community structure analysis showed that the bacterial genus Pseudomonas and the fungal genus Phialophora were both important in the degradation of BTEp-X. The fungal-bacterial consortia can enhance the biofiltration removal of BTEp-X vapors.

Asunto(s)

Bacterias , Derivados del Benceno , Reactores Biológicos , Filtración , Hongos , Xilenos , Xilenos/metabolismo , Xilenos/química , Filtración/métodos , Hongos/metabolismo , Derivados del Benceno/metabolismo , Reactores Biológicos/microbiología , Bacterias/metabolismo , Biodegradación Ambiental , Tolueno/metabolismo , Benceno/metabolismo , China , Biopelículas

RESUMEN

BACKGROUND: In the regeneration of waste oil, a strategical technological process for the European Union circular economy action plan, exhausted oils are regenerated to produce high performing oil bases. Aim of this work was to assess the exposure to benzene in plant workers during ordinary activities. METHODS: 59 workers, potentially exposed to benzene, and 9 administrative workers from an Italian plant were monitored for the whole work shift with personal air samplers; urinary benzene (BEN-U) and S-phenyl mercapturic acid (SPMA) were measured by mass spectrometry methods in end-shift urine samples. Different job tasks were identified among workers. RESULTS: Median (minimum-maximum) airborne exposures to benzene were <0.9 (<0.9-6.3) and <0.9 (<0.9-0.9) µg/m3, BEN-U and SPMA levels were 0.094 (<0.015-3.095) µg/L and 0.15 (<0.10-9.67) µg/g crt and 0.086 (0.034-0.712) µg/L and <0.10 (<0.10-3.19) µg/g creatinine in workers and administrative workers, respectively. No differences were found among job tasks and between workers and administrative workers, while higher levels were found in smokers than in non-smokers. For all job tasks, the exposure to benzene was always below occupational limit values. CONCLUSIONS: This study has investigated for the first time the exposure to benzene of workers employed in the re-refining of exhaust oil. The results showed that normal production activities in regenerating used oils do not pose a risk of exposure to benzene in workers.

Asunto(s)

Contaminantes Ocupacionales del Aire , Benceno , Monitoreo Biológico , Exposición Profesional , Humanos , Benceno/análisis , Exposición Profesional/análisis , Adulto , Masculino , Persona de Mediana Edad , Contaminantes Ocupacionales del Aire/análisis , Italia , Femenino , Industria del Petróleo y Gas , Acetilcisteína/orina , Acetilcisteína/análogos & derivados