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1.
Sci Total Environ ; 794: 148731, 2021 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-34217077

RESUMO

Hemocytes are critical to the immune defense system of bivalves, and polycyclic aromatic hydrocarbons (PAHs) can mediate the immunity of bivalves by affecting the apoptosis of hemocytes. However, the underlying mechanism is still unclear. Chlamys farreri, as an important economic bivalve, was selected as the research subject for this experimentation. The hemocytes were exposed to typical PAHs-benzopyrene (B[a]P) in vitro to explore the apoptosis mechanism through detecting oxidative stress and oxidative damage-related indicators, apoptosis pathway factors, and apoptosis rate within 24 h. The results showed that the reactive oxygen species (ROS) and benzo[a]pyrene-7,8-diol-9,10-epoxide (BPDE) content in hemocytes increased significantly under B[a]P exposure, while antioxidant genes, glutathione peroxidase content and total antioxidant capacity all showed a trend of first rising and subsequent falling. B[a]P also caused serious damage to DNA and lysosomal membrane stability. The proapoptotic factors genes in the mitochondrial apoptosis pathway were significantly up-regulated, and the anti-apoptotic gene Bcl-2 was significantly down-regulated. Besides, mitochondrial membrane potential stability was significantly reduced and caspase 9 enzyme activity was significantly improved with the B[a]P stimulation. The factors of death receptor pathway were also significantly up-regulated by B[a]P. Moreover, the expression levels of Mitogen-Activated Protein Kinases were also induced. The gene expression and enzyme activity of the caspase 3 and the apoptosis rate were significantly increased under B[a]P exposure. In conclusion, these results indicated that ROS was induced by B[a]P, and further triggered the oxidative stress and oxidative damage in hemocytes. B[a]P induced hemocyte apoptosis was mediated by both mitochondrial apoptosis pathway and death receptor apoptosis, and the activation of mitochondrial apoptosis pathway was affected by ROS. In addition, BPDE and MAPKs may play important roles in the B[a]P-mediated apoptosis pathway. This study deepens understanding of the apoptosis pathway and the immunotoxicity mechanism in bivalves hemocytes stimulated by persistent organic pollutants.


Assuntos
Hemócitos , Pectinidae , Animais , Apoptose , Benzo(a)pireno/toxicidade , Benzopirenos
2.
J Chem Phys ; 154(17): 175102, 2021 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-34241046

RESUMO

Polycyclic aromatic hydrocarbons (PAHs) are widely distributed in environments, and some of them are causative agents of human cancer. Previous studies concluded that benzo[a]pyrene-7,8-dione (BPQ), which is one kind of carcinogenic PAH metabolites, forms covalently bonded adducts with DNA, and the major adduct formed is a deoxyguanosine adduct. In this work, we investigate the interactions between BPQ and DNA molecules via first-principles calculations. We identify six possible DNA adducts with BPQ. In addition to the four adducts forming covalent bonds, there are two adducts bound purely by van der Waals (vdW) interactions. Remarkably, the two vdW-bound adducts have comparable, if not larger, binding energies as the covalent adducts. The results may help us gain more understanding of the interactions between PAH metabolites and DNA.


Assuntos
Benzopirenos/química , Adutos de DNA/química , Teoria da Densidade Funcional , Simulação de Dinâmica Molecular , Benzopirenos/metabolismo , Adutos de DNA/metabolismo , Estrutura Molecular
3.
Int J Mol Sci ; 22(11)2021 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-34199457

RESUMO

Polycyclic aromatic hydrocarbons (PAHs) are chemical compounds comprised of carbon and hydrogen molecules in a cyclic arrangement. PAHs are associated with risks to human health, especially carcinogenesis. One form of exposure to these compounds is through ingestion of contaminated food, which can occur during preparation and processing involving high temperatures (e.g., grilling, smoking, toasting, roasting, and frying) as well as through PAHs present in the soil, air, and water (i.e., environmental pollution). Differently from changes caused by microbiological characteristics and lipid oxidation, consumers cannot sensorially perceive PAH contamination in food products, thereby hindering their ability to reject these foods. Herein, the occurrence and biological effects of PAHs were comprehensively explored, as well as analytical methods to monitor their levels, legislations, and strategies to reduce their generation in food products. This review updates the current knowledge and addresses recent regulation changes concerning the widespread PAHs contamination in several types of food, often surpassing the concentration limits deemed acceptable by current legislations. Therefore, effective measures involving different food processing strategies are needed to prevent and reduce PAHs contamination, thereby decreasing human exposure and detrimental health effects. Furthermore, gaps in literature have been addressed to provide a basis for future studies.


Assuntos
Carcinogênese/efeitos dos fármacos , Poluição Ambiental/efeitos adversos , Alimentos/efeitos adversos , Hidrocarbonetos Policíclicos Aromáticos/efeitos adversos , Benzopirenos/efeitos adversos , Carcinogênese/genética , Carvão Vegetal/efeitos adversos , Culinária , Adutos de DNA/efeitos adversos , Análise de Alimentos , Manipulação de Alimentos , Humanos
4.
Pak J Biol Sci ; 24(2): 274-281, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33683058

RESUMO

BACKGROUND AND OBJECTIVE: The andaliman fruits have anti-inflammatory, antioxidant activity and a strong inhibition in antitumor activity. The purpose of this study was to analyze the effect of extract andaliman on rat's kidney and liver histology induced by benzopyrene. MATERIALS AND METHODS: The rats model of cancer-induced benzopyrene. This research consists of 5 groups; K-: Control, K+: Cancer model rats, P1: A dose of 100 mg per b.wt. per day of andaliman, P2: A dose of 200 mg per b.wt. per day and P3: A dose of 400 mg kg-1 b.wt., per day for 30 days. On the 31st day, performed surgically on the subjects. RESULTS: There were significant differences in the value of narrowing of the renal tubules (p<0.001), kidneys cells necrosis (p<0.01), hydrophilic degeneration (p<0.001), parenchymatous degeneration (p<0.01) and necrosis (p<0.001) in the liver after given the extract andaliman. CONCLUSION: Andaliman methanol extract repairs the damage of the liver and kidney of rats induced by benzopyrene. Andaliman can be recommended as a drug to repair the necrosis in the liver and kidneys caused by cancer.


Assuntos
Antineoplásicos/farmacologia , Rim/efeitos dos fármacos , Fígado/efeitos dos fármacos , Extratos Vegetais/farmacologia , Neoplasias do Colo do Útero/tratamento farmacológico , Zanthoxylum , Animais , Antineoplásicos/isolamento & purificação , Benzopirenos , Modelos Animais de Doenças , Feminino , Rim/patologia , Fígado/patologia , Metanol/química , Necrose , Extratos Vegetais/isolamento & purificação , Ratos , Solventes/química , Neoplasias do Colo do Útero/induzido quimicamente , Neoplasias do Colo do Útero/patologia , Zanthoxylum/química
5.
J Hazard Mater ; 406: 124306, 2021 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-33109409

RESUMO

Nanoplastics have recently become a worldwide concern as newly emerging airborne pollutants, which can associate with polycyclic aromatic hydrocarbons (PAHs) and form combined contaminant nanoparticles (CCNPs). After being inhaled in the respiratory system, the CCNPs would first encounter the mucous gel layer being rich in mucin. Herein, polystyrene-benzopyrene (PS@Bap) NPs were prepared as CCNPs model and their interaction with mucin and the resultant biological responses were studied. It was observed that mucin corona stably attached to the CCNPs surface, which significantly altered the fate of the CCNPs in lung epithelial cells (A 549 cell line). The mucin corona would 1) stably adsorbed on PS@Bap at the early stages of endocytosis until degraded during the lysosomal transport and maturation process, 2) delay intracellular trafficking of PS@Bap and the progress of Bap detached from PS, 3) enhance uptake of PS@Bap but reduce the cytotoxicity elicited by PS@Bap, as indicated by cell viability, generation of reactive oxygen species, impairment on mitochondrial function, and further cell apoptosis. In addition, in vivo study also verified the enhanced effect of PS on the development of an acute lung inflammatory response induced by Bap. This study highlights the significance of incorporating the effects of mucin for precisely assessing the respiratory system toxicity of nanoplastics based CCNPs in atmospheric environments.


Assuntos
Nanopartículas , Hidrocarbonetos Policíclicos Aromáticos , Benzopirenos , Microplásticos , Mucinas , Nanopartículas/toxicidade , Poliestirenos
6.
Int J Environ Health Res ; 31(2): 202-214, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31296039

RESUMO

Age-specific differences in the pharmacokinetics of benzo(a)pyrene (BaP) and its metabolite 3-hydroxybenzo(a)pyrene (3-OHBaP) potentially affect time courses of tissue concentration; however, the quantitative impact of these differences is not well characterized. Our objective was to quantify the effect of age-specific differences in physiological and biochemical parameters on the pharmacokinetics of BaP and 3-OHBaP from newborn at birth to adulthood following inhalation exposure. The time courses of BaP and 3-OHBaP were simulated by using a physiologically based pharmacokinetic model with Advanced Continuous Simulation Language (ACSLX). The concentrations of BaP increased with age in the liver but decreased with age in most tissues, urine, and blood. The concentrations of 3-OHBaP were the highest in the newborns. Our results also showed that the concentration of BaP has almost reached a steady state in the kidney, liver, lung, rapidly perfused tissues, slowly perfused tissues, and skin except for adipose tissues. However, the concentration of 3-OHBaP has reached a steady state in all tissues. This study suggests that age-specific parameters have an effect on the pharmacokinetics of BaP and 3-OHBaP. In particular, tissue concentration in the newborns is higher than other age groups, which indicates that the newborns are susceptible to environmental BaP exposure.


Assuntos
Envelhecimento/metabolismo , Benzo(a)pireno/farmacocinética , Benzopirenos/farmacocinética , Fígado/metabolismo , Modelos Biológicos , Fatores Etários , Vias de Eliminação de Fármacos , Humanos , Exposição por Inalação/efeitos adversos , Fígado/efeitos dos fármacos , Especificidade de Órgãos
7.
Planta ; 252(6): 107, 2020 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-33206238

RESUMO

MAIN CONCLUSION: Benzopyrene is rapidly incorporated and metabolized, and induces oxidative stress and activation of antioxidant enzymes, and CYP450 and GST metabolizing enzymes in Ulva lactuca. To analyze absorption and metabolism of benzo[a]pyrene (BaP) in Ulva lactuca, the alga was cultivated with 5 µM of BaP for 72 h. In the culture medium, BaP level rapidly decreased reaching a minimal level at 12 h and, in the alga, BaP level increased until 6 h, remained stable until 24 h, and decreased until 72 h indicating that BaP is being metabolized in U. lactuca. In addition, BaP induced an initial increase in hydrogen peroxide decreasing until 24 h, superoxide anions level that remained high until 72 h, and lipoperoxides that initially increased and decreased until 72 h, showing that BaP induced oxidative stress. Activities of antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), ascorbate peroxidase (AP), glutathione reductase (GR) and glutathione peroxidase (GP) were increased, whereas dehydroascorbate reductase (DHAR) activity was unchanged. The level of transcripts encoding these antioxidant enzymes was increased, but transcripts encoding DHAR remained unchanged. Interestingly, the activity of glutathione-S-transferase (GST) was also increased, and inhibitors of cytochrome P450 (CYP450) and GST activities enhanced the level of BaP in algal tissue, suggesting that these enzymes participate in BaP metabolism.


Assuntos
Benzopirenos , Regulação Enzimológica da Expressão Gênica , Estresse Oxidativo , Oxirredutases , Ulva , Benzopirenos/farmacologia , Sistema Enzimático do Citocromo P-450/genética , Sistema Enzimático do Citocromo P-450/metabolismo , Ativação Enzimática/efeitos dos fármacos , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Glutationa Transferase/genética , Glutationa Transferase/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Oxirredutases/genética , Ulva/efeitos dos fármacos , Ulva/enzimologia , Ulva/genética
8.
Toxicol Appl Pharmacol ; 404: 115180, 2020 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-32739527

RESUMO

Numerous studies conducted in the past have reported deaths in the human population due to cardiovascular diseases (CVD) on exposure to air particulate matter (APM). BP-1,6-quinone (BP-1,6-Q) is one of the significant components of APM. However, the mechanism(s) by which it can exert its toxicity in endothelial cells is not yet completely understood. NAD(P)H: quinone oxidoreductase-1 (NQO1) is expressed highly in myocardium and vasculature tissues of the heart and plays a vital role in maintaining vascular homeostasis. This study, demonstrated that BP-1,6-Q diminishes NQO1 enzyme activity in a dose-dependent manner in human EA.hy926 endothelial cells. The decrease in the NQO1 enzyme causes potentiation in BP-1,6-Q-mediated toxicity in EA.hy926 endothelial cells. The enhancement of NQO1 in endothelial cells showed cytoprotection against BP-1,6-Q-induced cellular toxicity, lipid, and protein damage suggesting an essential role of NQO1 in cytoprotection against BP-1,6-Q toxicity. Using various biochemical assays and genetic approaches, results from this study further demonstrated that NQO1 also plays a crucial role in BP-1,6-Q-induced production of reactive oxygen species (ROS). These findings will contribute to elucidating BP-1,6-Q mediated toxicity and its role in the development of atherosclerosis.


Assuntos
Benzopirenos/toxicidade , Células Endoteliais/efeitos dos fármacos , NAD(P)H Desidrogenase (Quinona)/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Benzopirenos/química , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Dicumarol/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Peróxido de Hidrogênio/metabolismo , Estrutura Molecular , NAD(P)H Desidrogenase (Quinona)/genética
9.
Cells ; 9(8)2020 07 22.
Artigo em Inglês | MEDLINE | ID: mdl-32708048

RESUMO

Resistance of cancer cells to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis represents the major hurdle to the clinical use of TRAIL or its derivatives. The discovery and development of lead compounds able to sensitize tumor cells to TRAIL-induced cell death is thus likely to overcome this limitation. We recently reported that marine actinomycetes' crude extracts could restore TRAIL sensitivity of the MDA-MB-231 resistant triple negative breast cancer cell line. We demonstrate in this study, that purified secondary metabolites originating from distinct marine actinomycetes (sharkquinone (1), resistomycin (2), undecylprodigiosin (3), butylcyclopentylprodigiosin (4), elloxizanone A (5) and B (6), carboxyexfoliazone (7), and exfoliazone (8)), alone, and in a concentration-dependent manner, induce killing in both MDA-MB-231 and HCT116 cell lines. Combined with TRAIL, these compounds displayed additive to synergistic apoptotic activity in the Jurkat, HCT116 and MDA-MB-231 cell lines. Mechanistically, these secondary metabolites induced and enhanced procaspase-10, -8, -9 and -3 activation leading to an increase in PARP and lamin A/C cleavage. Apoptosis induced by these compounds was blocked by the pan-caspase inhibitor QvD, but not by a deficiency in caspase-8, FADD or TRAIL agonist receptors. Activation of the intrinsic pathway, on the other hand, is likely to explain both their ability to trigger cell death and to restore sensitivity to TRAIL, as it was evidenced that these compounds could induce the downregulation of XIAP and survivin. Our data further highlight that compounds derived from marine sources may lead to novel anti-cancer drug discovery.


Assuntos
Actinobacteria/metabolismo , Organismos Aquáticos/metabolismo , Regulação para Baixo/efeitos dos fármacos , Descoberta de Drogas/métodos , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Metabolismo Secundário/fisiologia , Survivina/metabolismo , Ligante Indutor de Apoptose Relacionado a TNF/farmacologia , Proteínas Inibidoras de Apoptose Ligadas ao Cromossomo X/metabolismo , Apoptose/efeitos dos fármacos , Benzopirenos/metabolismo , Benzopirenos/farmacologia , Caspase 8/genética , Sobrevivência Celular/efeitos dos fármacos , Deleção de Genes , Células HCT116 , Humanos , Células Jurkat , Oxazinas/metabolismo , Oxazinas/farmacologia , Prodigiosina/análogos & derivados , Prodigiosina/metabolismo , Prodigiosina/farmacologia , Quinonas/metabolismo , Quinonas/farmacologia
10.
Sci Rep ; 10(1): 12136, 2020 07 22.
Artigo em Inglês | MEDLINE | ID: mdl-32699216

RESUMO

To reveal the impacts of smoking on genetic architecture of human body weight, we conducted a genome-wide association study on 5,336 subjects in four ethnic populations from MESA (The Multi-Ethnic Study of Atherosclerosis) data. A full genetic model was applied to association mapping for analyzing genetic effects of additive, dominance, epistasis, and their ethnicity-specific effects. Both the unconditional model (base) and conditional model including smoking as a cofactor were investigated. There were 10 SNPs involved in 96 significant genetic effects detected by the base model, which accounted for a high heritability (61.78%). Gene ontology analysis revealed that a number of genetic factors are related to the metabolic pathway of benzopyrene, a main compound in cigarettes. Smoking may play important roles in genetic effects of dominance, dominance-related epistasis, and gene-ethnicity interactions on human body weight. Gene effect prediction shows that the genetic effects of smoking cessation on body weight vary from different populations.


Assuntos
Peso Corporal , Estudo de Associação Genômica Ampla , Fumar/genética , Aterosclerose/patologia , Benzopirenos/química , Benzopirenos/metabolismo , Epistasia Genética , Grupos Étnicos/genética , Ontologia Genética , Genótipo , Humanos , Fenótipo , Polimorfismo de Nucleotídeo Único , Característica Quantitativa Herdável
12.
Mol Cell Biochem ; 474(1-2): 27-39, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32715408

RESUMO

Epidemiological studies have exhibited a strong correlation between exposure to air pollution and deaths due to vascular diseases such as atherosclerosis. Benzo-a-pyrene-1,6-quinone (BP-1,6-Q) is one of the components of air pollution. This study was to examine the role of GSH in BP-1,6-Q mediated cytotoxicity in human EA.hy96 endothelial cells and demonstrated that induction of cellular glutathione by a potent triterpenoid, CDDO-Im (1-[2-cyano-3-,12-dioxooleana-1,9(11)-dien-28-oyl]imidazole), protects cells against BP-1,6-Q induced protein and lipid damage. Incubation of EA.hy926 endothelial cells with BP-1,6-Q caused a significant increase in dose-dependent cytotoxicity as measured by LDH release assay and both apoptotic and necrotic cell deaths as measured by flow cytometric analysis. Incubation of EA.hy926 endothelial cells with BP-1,6-Q also caused a significant decrease in cellular GSH levels. The diminishment of cellular GSH by buthionine sulfoximine (BSO) potentiated BP-1,6-Q-induced toxicity significantly suggesting a critical involvement of GSH in BP-1,6-Q induced cellular toxicity. GSH-induction by CDDO-Im significantly protects cells against BP-1,6-Q induced protein and lipid damage as measured by protein carbonyl (PC) assay and thiobarbituric acid reactive substances (TBARS) assay, respectively. However, the co-treatment of cells with CDDO-Im and BSO reversed the cytoprotective effect of CDDO-Im on BP-1,6-Q-mediated lipid peroxidation and protein oxidation. These results suggest that induction of GSH by CDDO-Im might be the important cellular defense against BP-1,6-Q induced protein and lipid damage. These findings would contribute to better understand the action of BP-1,6-Q and may help to develop novel therapies to protect against BP-1,6-Q-induced atherogenesis.


Assuntos
Apoptose , Benzopirenos/efeitos adversos , Citoproteção , Endotélio Vascular/efeitos dos fármacos , Glutationa/metabolismo , Imidazóis/farmacologia , Ácido Oleanólico/análogos & derivados , Substâncias Protetoras/farmacologia , Células Cultivadas , Endotélio Vascular/metabolismo , Endotélio Vascular/patologia , Humanos , Peroxidação de Lipídeos , Necrose , Ácido Oleanólico/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo
13.
Food Chem ; 328: 127117, 2020 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-32474240

RESUMO

This study was aimed to reduce the concentrations of benzopyrene (BaP) and acrylamide (ACR) in roasted coffee beans by corona discharge plasma jet (CDPJ). The initial concentrations of BaP and ACR in roasted beans were decreased by 53.6% and 32.0%, respectively, following CDPJ (powered by 20 kV DC/1.5 A) treatment for 60 min. The levels of total solid, total acid, chlorogenic acid, caffeine, trigonelline, and pH were insignificantly changed upon CDPJ treatment compared to controls. However, the concentration of total phenolic content and Agtron color values were altered significantly. The treatment of beans did not alter descriptive sensory properties of the corresponding coffee brews, except aroma and aftertaste characteristics. As the treatment time increased from 15 to 60 min, scores for aroma profiles in PCA plot were shifted from right to left, although overlapping was observed between 15- and 30-min-treated samples. Additionally, none of the treated samples were discriminated from the control by electronic tongue.


Assuntos
Acrilamida/química , Benzopirenos/química , Café/química , Alcaloides/análise , Fenômenos Bioquímicos , Cafeína/análise , Ácido Clorogênico/análise , Culinária , Nariz Eletrônico , Temperatura Alta
14.
Chem Res Toxicol ; 33(7): 1770-1779, 2020 07 20.
Artigo em Inglês | MEDLINE | ID: mdl-32227843

RESUMO

High-throughput in vitro reporter gene assays are increasingly applied to assess the potency of chemicals to alter specific cellular signaling pathways. Genetically modified reporter gene cell lines provide stable readouts of the activation of cellular receptors or transcription factors of interest, but such reporter gene assays have been criticized for not capturing cellular metabolism. We characterized the metabolic activity of the widely applied AREc32 (human breast cancer MCF-7), ARE-bla (human liver cancer HepG2), and GR-bla (human embryonic kidney HEK293) reporter gene cells in the absence and in the presence of benzo[a]pyrene (BaP), an AhR ligand known to upregulate cytochrome P450 in vitro and in vivo. We combined fluorescence microscopy with chemical analysis, real-time PCR, and ethoxyresorufin-O-deethylase activity measurements to track temporal changes in BaP and its metabolites in the cells and surrounding medium over time in relation to the expression and activity of metabolic enzymes. Decreasing BaP concentrations and formation of metabolites agreed with the high basal CYP1 activity of ARE-bla and the strong CYP1A1 mRNA induction in AREc32, whereas BaP concentrations were constant in GR-bla, in which neither metabolites nor CYP1 induction was detected. The study emphasizes that differences in sensitivity between reporter gene assays may be caused not only by different reporter constructs but also by a varying biotransformation rate of the evaluated parent chemical. The basal metabolic capacity of reporter gene cells in the absence of chemicals is not a clear indication because we demonstrated that the metabolic activity can be upregulated by AhR ligands during the assay. The combination of methods presented here is suitable to characterize the metabolic activity of cells in vitro and can improve the interpretation of in vitro reporter gene effect data and extrapolation to in vivo human exposure.


Assuntos
Benzopirenos/farmacologia , Bioensaio , Citocromo P-450 CYP1A1/genética , Citocromo P-450 CYP1A1/metabolismo , Modelos Biológicos , Genes Reporter , Células HEK293 , Células Hep G2 , Humanos , Células MCF-7 , RNA Mensageiro/metabolismo
15.
Microbiologyopen ; 9(7): e1039, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32282132

RESUMO

The presence of polycyclic aromatic hydrocarbons (PAHs) in marine environments as a result of contamination is an environmental concern, especially in regions where oil spills such as the Deepwater Horizon have occurred. While numerous PAHs have been studied for their effects on microbes, the family of dibenzopyrenes has yet to be investigated. In this preliminary study, the impacts of these molecules on the community structure of a bacterial consortium isolated from oil-impacted Gulf of Mexico sediment were examined using high-throughput sequencing, demonstrating intriguing negative impacts on species diversity and abundance. While no measurable degradation of the dibenzopyrenes was observed after 28-day incubation, the abundance of known oil-degrading bacteria from orders such as Oceanospirillales, Caulobacterales, Sphingomonadales, and Nitrosococcales were shown to be enhanced. Of the five isomers of dibenzopyrene studied, dibenzo[a,h]pyrene supported the fewer number of microbial species suggesting the isomer was more toxic compared to the other isomers.


Assuntos
Bactérias/metabolismo , Benzopirenos/análise , Sedimentos Geológicos/química , Sedimentos Geológicos/microbiologia , Hidrocarbonetos Policíclicos Aromáticos/análise , Poluentes Químicos da Água/análise , Benzopirenos/metabolismo , Golfo do México , Poluição por Petróleo/efeitos adversos , Hidrocarbonetos Policíclicos Aromáticos/metabolismo , Água do Mar/química , Água do Mar/microbiologia , Poluentes Químicos da Água/metabolismo
16.
Anal Chem ; 92(10): 7200-7208, 2020 05 19.
Artigo em Inglês | MEDLINE | ID: mdl-32233451

RESUMO

The health impact of environmental pollution involving an increase in human diseases has been subject to extensive study in recent decades. The methodology in biomimetic investigation of these pathophysiologic events is still in progress to uncover the gaps in knowledge associated with pollution and its influences on health. Herein, we describe a comprehensive evaluation of environmental pollutant-caused lung inflammation and injury using a microfluidic pulmonary alveolus platform with alveolar-capillary interfaces. We performed a microfluidic three-dimensional coculture with physiological microenvironment simulation at microscale control and demonstrated a reliable reconstruction of tissue layers including alveolar epithelium and microvascular endothelium with typical mechanical, structural, and junctional integrity, as well as viability. On-chip detection and analysis of pulmonary alveolus responses focusing on various inflammatory and injurious dynamics to the respective pollutant stimulations were achieved in the coculture-based microfluidic pulmonary alveolus model, in comparison with common on-chip monoculture and off-chip culture tools. We confirmed the synergistic effects of the epithelial and endothelial interfaces on the stimuli resistance and verified the importance of creating complex tissue microenvironments in vitro to explore pollution-involved human pathology. We believe the microfluidic approach presents great promise in environmental monitoring, drug discovery, and tissue engineering.


Assuntos
Benzopirenos/efeitos adversos , Poluentes Ambientais/efeitos adversos , Técnicas Analíticas Microfluídicas , Nicotina/efeitos adversos , Pneumonia/induzido quimicamente , Alvéolos Pulmonares/efeitos dos fármacos , Benzopirenos/química , Células Cultivadas , Técnicas de Cocultura , Citocinas/análise , Citocinas/metabolismo , Poluentes Ambientais/química , Humanos , Microscopia Confocal , Estrutura Molecular , Nicotina/química , Pneumonia/metabolismo , Pneumonia/patologia , Alvéolos Pulmonares/metabolismo , Alvéolos Pulmonares/patologia , Espécies Reativas de Oxigênio/metabolismo
17.
Asian Pac J Cancer Prev ; 21(2): 295-300, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-32102502

RESUMO

OBJECTIVE: Silica and Benzo(a)pyrene are listed as carcinogens. This study aims to explore Cyclin D1, CDK4 and difference of cell cycle adjusted by MAPK signal transduction pathway in silica and B(a)P-induced malignant transformation of human embryonic lung fibroblasts. METHODS: Activity of the subfamily (ERK, p38 and JNK) of mitogen-activated protein kinase (MAPK), cyclin D1 and CDK4 (cyclin dependent kinase) were evaluated using Human embryonic lung fibroblast (HELF) purchased from the cell room, basic research institute, Chinese Academy of Medical Sciences. The expression of cyclin D1 and CDK4 (cyclin dependent kinase) were measured in silica and B(a)P induced malignant using Western blot (WB) assay. RESULT: P-ERK and P-JNK expression increased significantly (P<0.01), while CDK4 and P-p38 expression decreased (P<0.01, P<0.05) in silica-induced malignant transformation cells compared with the control group. P-ERK, P-JNK and Cyclin D1 expression increased (P<0.01, P<0.01, P<0.05) in B(a)P-induced group compared with the control group. P-ERK and P-JNK expression decreased (P<0.01), while P-p38, Cyclin D1 and CDK4 expression increased (P<0.05, P<0.05, P<0.01) in B(a)P-induced group compared with the silica-induced group. CONCLUSION: MAPK and cyclin D1/CDK4 activation expressed differently in human embryo lung fibroblasts malignant transformation induced by silica and benzopyrene.


Assuntos
Benzopirenos/efeitos adversos , Transformação Celular Neoplásica/patologia , Ciclina D1/metabolismo , Quinase 4 Dependente de Ciclina/metabolismo , Fibroblastos/patologia , Pulmão/patologia , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Dióxido de Silício/efeitos adversos , Ciclo Celular , Transformação Celular Neoplásica/efeitos dos fármacos , Transformação Celular Neoplásica/metabolismo , Células Cultivadas , Ciclina D1/genética , Quinase 4 Dependente de Ciclina/genética , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Humanos , Pulmão/efeitos dos fármacos , Pulmão/embriologia , Pulmão/metabolismo , Proteínas Quinases Ativadas por Mitógeno/genética , Transdução de Sinais
18.
Toxicol Lett ; 324: 54-64, 2020 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-32007588

RESUMO

The aims of this work were to assess the PAH exposure among roofers and to identify relevant biomarkers for monitoring occupational exposure. Several campaigns were conducted between 2004 and 2017, with 28 individual air samples and 240 urinary samples collected from 73 roofers. Seventeen parent PAHs and 14 urinary biomarkers, metabolites of pyrene (1-OHP), benzo(a)pyrene (3-OHBaP and TetraolBaP), naphthalene (1- and 2-naphtols), fluorene (1- 2- 3- 9-fluorenols) and phenanthrene (1- 2- 3- 4- 9-phenanthrols), were analysed. Three exposure groups were considered: soft-applied roofing using polymer-modified bitumen ("PMB"), hot-applied roofing using oxidized bitumen ("OB") and the tearing off of old roof coatings containing coal tar ("CT"). The PAHs containing 2-3 rings were much more abundant, and the highest airborne levels were observed in the "CT" group. The biomonitoring results were consistent with these results, with a large predominance of 2-3 ring PAH metabolites. 1-OHP, 3-fluorenol and 2-phenanthrol were better correlated with airborne levels and less influenced by smoking than the other metabolites. Conversely, 1-/2-naphtol levels were heavily influenced by smoking and not correlated with airborne naphthalene levels. Moreover, 3-OHBaP and TetraolBaP levels were very low when applying bitumen membranes, and much higher exposures were observed during tear-off activities. In this context, the recommended strategy for roofer biomonitoring should include 1-OHP, fluorenols and phenanthrols, as well as carcinogenic BaP metabolites (3-OHBaP or TetraolBaP) when evaluating the occupational exposure of roofers that are tearing off old roof coatings.


Assuntos
Monitoramento Biológico/métodos , Exposição Ocupacional/análise , Hidrocarbonetos Policíclicos Aromáticos/urina , Adulto , Poluentes Ocupacionais do Ar/análise , Benzopirenos/metabolismo , Biomarcadores/urina , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Material Particulado/análise , Pirenos/metabolismo , Adulto Jovem
19.
Toxicol Lett ; 322: 120-130, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-31953210

RESUMO

Strong epidemiological evidence supports the association between increased air pollution and the risk of developing atherosclerotic cardiovascular diseases (CVDs). However, the mechanism remains unclear. As an environmental air pollutant and benzo-a-pyrene (BP) metabolite, BP-1,6-quinone (BP-1,6-Q) is present in the particulate phase of air pollution. This study was undertaken to examine the redox activity of BP-1,6-Q and mechanisms associated with it using EA.hy926 endothelial cells. BP-1,6-Q at 0.01-1 µM significantly stimulated the production of reactive oxygen species (ROS)·in intact cells and isolated mitochondria. Furthermore, BP-1,6-Q-induced ROS was altered by mitochondrial electron transport chain (METC) inhibitors of complex I (rotenone) and complex III (antimycin A), denoting the involvement of mitochondrial electron transport chain (METC) in BP-1,6-Q mediated ROS production. In METC deficient cells, interestingly, BP-1,6-Q-mediated ROS production was enhanced, suggesting that overproduction of ROS by BP-1,6-Q is not only produced from mitochondria but can also be from the cell outside of mitochondria (extramitochondrial). BP-1,6-Q also triggered endothelial-monocyte interaction and stimulated expression of vascular adhesion molecule-1 (VCAM-1). In conclusion, these results demonstrate that BP-1,6-Q can generate ROS within both mitochondria and outside of mitochondria, resulting in stimulation of adhesion of monocytes to endothelial cells, a key event in the pathogenesis of atherosclerosis.


Assuntos
Benzopirenos/toxicidade , Células Endoteliais/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Adesão Celular/efeitos dos fármacos , Linhagem Celular , Técnicas de Cocultura , Complexo de Proteínas da Cadeia de Transporte de Elétrons/metabolismo , Células Endoteliais/metabolismo , Células Endoteliais/patologia , Humanos , Mitocôndrias/metabolismo , Mitocôndrias/patologia , Monócitos/metabolismo , Oxirredução , Transdução de Sinais , Molécula 1 de Adesão de Célula Vascular/genética , Molécula 1 de Adesão de Célula Vascular/metabolismo
20.
Cancer Prev Res (Phila) ; 13(4): 357-366, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31969344

RESUMO

We previously reported that the environmental pollutant and tobacco smoke constituent dibenzo[def,p]chrysene (DBP) induced DNA damage, altered DNA methylation and induced oral squamous cell carcinoma (OSCC) in mice. In the present study, we showed that 5% dietary black raspberry (BRB) significantly reduced (P < 0.05) the levels of DBP-DNA adducts in the mouse oral cavity with comparable effect to those of its constitutes. Thus, only BRB was selected to examine if aberrant DNA methylation induced by DBP can be altered by BRB. Using comparative genome-wide DNA methylation analysis, we identified 479 hypermethylated and 481 hypomethylated sites (q < 0.01, methylation difference >25%) between the oral tissues of mice treated with DBP and fed control diet or diet containing BRB. Among the 30 differential methylated sites (DMS) induced by DBP, we found DMS mapped to Fgf3, Qrich2, Rmdn2, and Cbarp were hypermethylated by BRB whereas hypomethylated by DBP at either the exact position or proximal sites; DMS mapped to Vamp3, Ppp1rB1, Pkm, and Zfp316 were hypomethylated by BRB but hypermethylated by DBP at proximal sites. In addition to Fgf3, 2 DMS mapped to Fgf4 and Fgf13 were hypermethylated by BRB; these fibroblast growth factors are involved in regulation of the epithelial-mesenchymal transition (EMT) pathway as identified by IPA. Moreover, BRB significantly reduced (P < 0.05) the tumor incidence from 70% to 46.7%. Taken together, the inhibitory effects of BRB on DNA damage combined with its effects on epigenetic alterations may account for BRB inhibition of oral tumorigenesis induced by DBP. SIGNIFICANCE: We provided mechanistic insights that can account for the inhibition of oral tumors by BRB, which could serve as the framework for future chemopreventive trials for addicted smokers as well as non- or former smokers who are exposed to environmental carcinogens.


Assuntos
Benzopirenos/toxicidade , Epigênese Genética , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Neoplasias Bucais/tratamento farmacológico , Extratos Vegetais/farmacologia , Rubus/química , Poluição por Fumaça de Tabaco/prevenção & controle , Animais , Apoptose , Biomarcadores Tumorais/genética , Carcinógenos/toxicidade , Carcinoma de Células Escamosas/induzido quimicamente , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patologia , Proliferação de Células , Metilação de DNA , Feminino , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Neoplasias Bucais/induzido quimicamente , Neoplasias Bucais/genética , Neoplasias Bucais/patologia , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto
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