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1.
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
2.
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
3.
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
4.
J Chromatogr B Analyt Technol Biomed Life Sci ; 1118-1119: 187-193, 2019 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-31055084

RESUMO

Urinary 3-hydroxybenzo[a]pyrene (3-OH-BaP) is a known biomarker for human exposure to carcinogenic polycyclic aromatic hydrocarbons (PAH). In this work, a new method for the ultra-sensitive quantification of this biomarker has been developed using the hyphenation of gas chromatography and atmospheric pressure laser ionization-mass spectrometry (GC-APLI-MS). In combination with an advanced sample preparation, a limit of detection (LOD) of 0.6 pg/L was achieved which is an improvement by a factor of at least 28 compared with existing methods. The limit of quantification (LOQ) is 1.8 pg/L. With this set-up 3-OH-BaP could be analyzed in urine samples of 7 smokers and 7 non-smokers. Concentrations ranged from 37 to 270 pg/L for non-smokers and from 374 to 1171 pg/L for smokers. For the first time, 3-OH-BaP was quantifiable in all non-smoker samples as no value was below the LOQ. Correlation of the urinary 3-OH-BaP values with the number of daily smoked cigarettes and with urinary cotinine values shows a clear relationship between 3-OH-BaP content and smoking habits. This innovative analytical method enables monitoring of low levels of the biomarker 3-OH-BaP in urine of non-occupationally exposed individuals including smokers, the general population with background PAH exposure and cohorts of low exposition such as newborns and children.


Assuntos
Benzopirenos/análise , Cromatografia Gasosa-Espectrometria de Massas/métodos , Exposição por Inalação/análise , Fumar/urina , Adulto , Biomarcadores/urina , Alemanha , Humanos , Limite de Detecção , Modelos Lineares , Reprodutibilidade dos Testes , Poluição por Fumaça de Tabaco/análise
5.
Chem Biol Interact ; 302: 135-142, 2019 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-30776357

RESUMO

Riboflavin (Rf) or vitamin B2 is a known photosensitizer whose photophysical and photochemical properties are well established. Aminophylline (Am) is a phosphodiesterase inhibitor and is currently used as a bronchodilator. Although there are several reports of haemolytic and proteolytic interaction of photoilluminated riboflavin with aminophylline, the cytotoxicity of this system against malignant tissue is not well defined and fully unravelled. Here, we are evaluating anticancer activity of this system against B(a)P induced lung carcinoma in swiss albino mice. We observed marked increment in the level of cellular redox scavengers as well as oxidative stress markers. A significant DNA damage was observed using comet assay. Histopathological studies further confirmed induction of apoptosis in lung tissues of Am-Rf treated animals. Scanning electron microscopy revealed altered surface morphology of the malignant tissue, which characteristically improved in the treatment group. Since malignancy is characterised by compromised redox status, therefore, further increment in ROS due to the action of this system derives cellular system towards extensive macromolecular damage and consequent ROS mediated apoptosis. We anticipate the usage of this system in developing efficient photodynamic therapy against lung cancer that can be clinically realised.


Assuntos
Aminofilina/farmacologia , Apoptose/efeitos dos fármacos , Neoplasias Pulmonares/patologia , Fármacos Fotossensibilizantes/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Riboflavina/farmacologia , Aminofilina/uso terapêutico , Animais , Benzopirenos/toxicidade , Dano ao DNA/efeitos dos fármacos , Luz , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , Pulmão/patologia , Neoplasias Pulmonares/induzido quimicamente , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/veterinária , Camundongos , Estresse Oxidativo/efeitos dos fármacos , Fotoquimioterapia , Fármacos Fotossensibilizantes/uso terapêutico , Riboflavina/uso terapêutico
6.
Int J Mol Sci ; 20(3)2019 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-30691106

RESUMO

Pollution-induced skin damage results in oxidative stress; cellular toxicity; inflammation; and, ultimately, premature skin aging. Previous studies suggest that the activation of autophagy can protect oxidation-induced cellular damage and aging-like changes in skin. In order to develop new anti-pollution ingredients, this study screened various kinds of natural extracts to measure their autophagy activation efficacy in cultured dermal fibroblast. The stimulation of autophagy flux by the selected extracts was further confirmed both by the expression of proteins associated with the autophagy signals and by electron microscope. Crepidiastrum denticulatum (CD) extract treated cells showed the highest autophagic vacuole formation in the non-cytotoxic range. The phosphorylation of adenosine monophosphate kinase (AMPK), but not the inhibition of mammalian target of rapamycin (mTOR), was observed by CD-extract treatment. Its anti-pollution effects were further evaluated with model compounds, benzo[a]pyrene (BaP) and cadmium chloride (CdCl2), and a CD extract treatment resulted in both the protection of cytotoxicity and a reduction of proinflammatory cytokines. These results suggest that the autophagy activators can be a new protection regimen for anti-pollution. Therefore, CD extract can be used for anti-inflammatory and anti-pollution cosmetic ingredients.


Assuntos
Asteraceae/química , Poluentes Ambientais/efeitos adversos , Células Epidérmicas/citologia , Extratos Vegetais/farmacologia , Proteínas Quinases Ativadas por AMP/metabolismo , Autofagia , Benzopirenos/efeitos adversos , Cloreto de Cádmio/efeitos adversos , Células Cultivadas , Citocinas/metabolismo , Células Epidérmicas/efeitos dos fármacos , Células Epidérmicas/metabolismo , Fibroblastos/citologia , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Microscopia Eletrônica de Transmissão , Estresse Oxidativo/efeitos dos fármacos , Fosforilação , Extratos Vegetais/química , Serina-Treonina Quinases TOR/metabolismo
7.
Int J Hyg Environ Health ; 222(1): 84-88, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30172597

RESUMO

INTRODUCTION: Firefighters have occupational exposure to toxic compounds during firefighting, but not only. Surface contamination of equipment has never been studied in French firefighters. MATERIALS AND METHODS: This study measured the surface load in benzo [a]pyrene (BaP), a carcinogenic polycyclic aromatic hydrocarbon, on the outer surface of fire jackets, personal protective equipment and tools used by firefighters after a live fire training in a closed environment. The effectiveness of a standard jacket washing procedure on BaP contamination was assessed. RESULTS: A single training session was responsible for a BaP deposit of 113.75 ±â€¯45.03µg/m2 on exposed fire jacket material. After a single session, the deposit of BaP found on PPE and tools was measured on different surfaces ranged from 12 to 157 µg/m2. After multiple training sessions, a cumulative effect was suspected. The current PPE cleaning and maintenance procedures does not appear to effectively reduce contamination. CONCLUSION: French firefighters' exposure during in a live-fire training session in fire simulator is responsible for exposure to BaP. The estimated load of BaP on the outer surface of fire jackets could potentially have acute and chronic effects if absorbed in one's body. Further studies are needed to better understand individual French firefighters' exposure and determine appropriate measures to prevent contamination. It will be also be necessary find maintenance procedures that significantly reduce the BaP load.


Assuntos
Benzopirenos/análise , Bombeiros , Exposição Ocupacional/análise
8.
Genes Genomics ; 41(1): 113-123, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30242742

RESUMO

Benzo[a]pyrene (BaP) is one of the most studied targets among polycyclic aromatic hydrocarbons (PAHs). Because of the complexity of the toxicity mechanism in BaP, little is known about the molecular mechanism at the level of transcription of BaP in marine fishes. The primary objective of this study was to investigate the molecular basis of the effects of BaP on marine fish, using Mugilogobius chulae (Smith 1932) as the model. A closed colony of M. chulae was used for the BaP toxicity test. Two fish liver samples per replicate from each group were excised and blended into one sample by pooling an equal amount of liver tissue. Total RNA of all samples was extracted separately. Equal quantities of total RNA from the three replicates of the two groups were pooled for sequencing. The sequencing cDNA libraries were sequenced using Illumina HiSeq 2000 system. Differentially expressed genes were detected with the DEGSeq R package. In total, 52,364,032 and 53,771,748 clean nucleotide reads were obtained in the control and BaP-exposed libraries, respectively, with N50 lengths of 1277 and 1288 bp, respectively. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses revealed a significant enrichment of genes related to detoxification, transportation, and lipid metabolism. We also identified, for the first time, an association between endoplasmic reticulum dysfunction and lipid metabolism resulting from BaP exposure. Using quantitative real-time PCR, some effective molecular biomarkers for monitoring of BaP-polluted seawater were identified. The results demonstrate that BaP enhanced the expression of genes involved in detoxification in M. chulae and inhibited that of genes related to lipid metabolism, possibly by suppressing the expression of numerous ER-related genes involved in fat digestion and absorption.


Assuntos
Benzopirenos/toxicidade , Peixes/genética , Estresse Fisiológico , Transcriptoma , Poluentes da Água/toxicidade , Animais , Peixes/metabolismo , Perfilação da Expressão Gênica
9.
Tob Control ; 28(2): 181-188, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-29807946

RESUMO

BACKGROUND: Studies that assess waterpipe tobacco smoking behaviour and toxicant exposure generally use controlled laboratory environments with small samples that may not fully capture real-world variability in human behaviour and waterpipe products. This study aimed to conduct real-time sampling of waterpipe tobacco use in natural environments using an in situ device. METHODS: We used the REALTIME sampling instrument: a validated, portable, self-powered device designed to sample automatically a fixed percentage of the aerosol flowing through the waterpipe mouthpiece during every puff. We recruited participants at café and home settings in Jordan and measured puffing behaviour in addition to inhalation exposure of total particulate matter (TPM), carbon monoxide (CO), nicotine, polycyclic aromatic hydrocarbons and volatile aldehydes. We correlated total inhaled volume with five selected toxicants and calculated the regression line of this relationship. RESULTS: Averaged across 79 singleton sessions (52% male, mean age 27.0, 95% home sessions), sessions lasted 46.9 min and participants drew 290 puffs and inhaled 214 L per session. Mean quantities of inhaled toxicants per session were 1910 mg TPM, 259 mg CO, 5.0 mg nicotine, 117 ng benzo[a]pyrene and 198 ng formaldehyde. We found positive correlations between total inhaled volume and TPM (r=0.472; p<0.001), CO (r=0.751; p<0.001), nicotine (r=0.301, p=0.035) and formaldehyde (r=0.526; p<0.001), but a non-significant correlation for benzo[a]pyrene (r=0.289; p=0.056). CONCLUSIONS: In the natural environment, waterpipe tobacco users inhale large quantities of toxicants that induce tobacco-related disease, including cancer. Toxicant content per waterpipe session is at least equal, but for many toxicants several magnitudes of order higher, than that of a cigarette. Health warnings based on early controlled laboratory studies were well founded; if anything our findings suggest a greater exposure risk.


Assuntos
Benzopirenos/análise , Monóxido de Carbono/análise , Formaldeído/análise , Exposição por Inalação/estatística & dados numéricos , Nicotina/análise , Material Particulado/análise , Fumaça/análise , Cachimbos de Água , Adulto , Feminino , Humanos , Masculino , Adulto Jovem
10.
Environ Pollut ; 246: 198-206, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30551038

RESUMO

In the present work, we analyzed the concentration patterns of 20 Polycyclic Aromatic Hydrocarbons (PAHs) in 25 surface sediments and 11 sediment cores from the northern part of Taihu Lake, China. Three of the cores were dated based on 137Cs activity for the deposition age of the sediment. The spatial distributions of the PAH concentrations show that the inflow rivers into Zhushan Bay and Meiliang Bay were the main pathway for PAHs and sediment input to the northern part of the lake. This results in substantially higher PAH concentrations (up to 5000 ng/g) and sedimentation rates (higher than the average of 3-4 mm/a) in the area close to the river outlets. In addition, results also show that PAH concentrations in the sediments considerably increased from the early 1960s, but the decreasing concentrations in the upper layers of the sediment could be attributed to the introduction of measures on environmental improvement from ca. 2000. There were both anthropogenic and biogenic origins of perylene in the lake sediments, which were distinguished based on spatial distribution patterns and also the concentration proportions of perylene to the sum of the 20 PAHs. In the cores collected close to river outlets, the concentration proportions of perylene typically range from 0.02 to 0.18 and there are significant positive linear correlations between the concentration of perylene and three anthropogenic PAHs (Benzo[a]pyrene, Benzo[e]pyrene, Pyrene), suggesting that perylene was dominated by anthropogenic input. However, the cores collected further away from the river outlets show the concentration proportions between 0.13 and 0.96, and present significant negative correlations or no correlations between perylene and the three PAHs, suggesting that perylene was mainly formed by biogenic activities. Furthermore, the different perylene sources accompanied with the location distributions imply that anthropogenic activities could inhibit its biogenic formation.


Assuntos
Monitoramento Ambiental/métodos , Sedimentos Geológicos/química , Lagos/química , Perileno/análise , Hidrocarbonetos Policíclicos Aromáticos/análise , Poluentes Químicos da Água/análise , Benzo(a)pireno/análise , Benzopirenos/análise , China , Pirenos/análise , Rios/química
11.
Chemosphere ; 219: 268-276, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30543962

RESUMO

SO2 and PAHs are well-known pollutants of coal burning and significant contributors to haze episodes. The purpose of the study is to determine whether the combined effects of SO2 and BaP are synergetic and to investigate the pro-fibrotic influences and possible mechanism from the aspect of microRNAs. In the present study cellular metabolic activity of BEAS-2B was assessed using MTT probe. C57BL/6 mice were exposed to BaP (40 mg/kg b.w.) for 5 days or SO2 (7 mg/m3) inhalation for 4 weeks alone or together. Lung tissues were processed for histology to assess pulmonary fibrosis. The protein level of pulmonary pro-fibrotic genes (Col1a1, Col3a1, alpha-SMA, fibronectin) and TGFßR2 were analyzed by Western blot and immunofluorescence in vivo and in vitro. Furthermore, we clarified that the microRNA expression of mir-30c-1-3p by real-time RT-PCR. The luciferase reporter assay was used to determine the binding sites of mir-30c-1-3p in the 3'-UTR of TGFßR2. It was confirmed that SO2 and BaP acted together to produce synergistic effects in cellular metabolic activity. Coexisting of SO2 and BaP increased the protein expression of pro-fibrotic genes and TGFßR2 and decreased mir-30c-1-3p in vivo and in vitro. Dual-luciferase reporter gene assays showed that TGFßR2 was a validated target of mir-30c-1-3p. All above results demonstrated that mir-30c-1-3p was involved in the synergistic pro-fibrotic effects of SO2 and BaP in lung via targeting TGFßR2. This work implies the potential risk of pulmonary fibrosis from the co-existence of SO2 and PAHs and provides new insights into the molecular markers for relevant diseases.


Assuntos
Benzopirenos/farmacologia , Camundongos Endogâmicos C57BL , MicroRNAs/metabolismo , Hidrocarbonetos Policíclicos Aromáticos/farmacologia , Fibrose Pulmonar/induzido quimicamente , Receptor do Fator de Crescimento Transformador beta Tipo II/metabolismo , Dióxido de Enxofre/farmacologia , Regiões 3' não Traduzidas , Animais , Sítios de Ligação , Camundongos , MicroRNAs/farmacologia , Fibrose Pulmonar/genética , Receptor do Fator de Crescimento Transformador beta Tipo II/análise , Receptor do Fator de Crescimento Transformador beta Tipo II/antagonistas & inibidores
12.
ACS Sens ; 3(12): 2716-2725, 2018 12 28.
Artigo em Inglês | MEDLINE | ID: mdl-30507116

RESUMO

Environmental pollution is one of the largest sources responsible for human diseases and premature death worldwide. However, the methodological development of a spatiotemporally controllable and high-throughput investigation of the environmental pollution-induced biological injury events is still being explored. In this study, we describe a chemical gradient generator-aided microfluidic cell system for the dynamic study of representative environmental pollutant-induced bronchial epithelium injury in a throughput manner. We demonstrated the stability and reliability of operation-optimized microfluidic system for precise and long-term chemical gradient production. We also performed a microenvironment-controlled microfluidic bronchial epithelium construction with high viability and structure integration. Moreover, on-chip investigation of bronchial epithelium injury by benzopyrene stimulation with various concentrations can be carried out in the single device. The varying bronchial inflammatory and cytotoxic responses were temporally monitored and measured based on the well-established system. The benzopyrene directionally led the bronchial epithelium to present observable cell shrinkage, cytoskeleton disintegration, Caspase-3 activation, overproduction of reactive oxygen species, and various inflammatory cytokine (TNF-α, IL-6, and IL-8) secretion, suggesting its significant inflammatory and cytotoxic effects on respiratory system. We believe the microfluidic advancement has potential applications in the fields of environmental monitoring, tissue engineering, and pharmaceutical development.


Assuntos
Benzopirenos/toxicidade , Brônquios/efeitos dos fármacos , Células Epiteliais/efeitos dos fármacos , Epitélio/efeitos dos fármacos , Dispositivos Lab-On-A-Chip , Brônquios/citologia , Caspase 3/metabolismo , Linhagem Celular , Ensaio de Imunoadsorção Enzimática , Desenho de Equipamento , Humanos , Interleucina-6/análise , Interleucina-6/metabolismo , Interleucina-8/análise , Interleucina-8/metabolismo , Microscopia Confocal/métodos , Microscopia de Fluorescência/métodos , Espécies Reativas de Oxigênio/metabolismo , Fator de Necrose Tumoral alfa/análise , Fator de Necrose Tumoral alfa/metabolismo
13.
Chem Res Toxicol ; 31(11): 1111-1118, 2018 11 19.
Artigo em Inglês | MEDLINE | ID: mdl-30260214

RESUMO

Ovarian cancer ranked second in incidence among gynecologic cancers, but it causes more deaths than any other gynecologic cancer; at present there is no curative treatment beyond surgery. Animal models that employ carcinogens found in the human environment can provide a realistic platform to understand the mechanistic basis for disease development and to design rational chemopreventive/therapeutic strategies. We and others have shown that the administration of the environmental pollutant and tobacco smoke constituent dibenzo[ def,p]chrysene (DBP) to mice by several routes of exposure can induce tumors in multiple sites including the ovary. In the present study we compared, for the first time, the tumorigenicity and DNA damage induced by DBP and its metabolites DBP-dihydrodiol (DBPDHD) and DBP-dihydrodiol epoxide (DBPDE) in the mouse ovary. Compounds were dissolved in dimethyl sulfoxide (DMSO) as the vehicle and administered by topical application into the mouse oral cavity three times per week for 38 weeks. No tumors were observed in mice treated with DMSO. At equal dose (24 nmol/30 µL DMSO), the incidence of ovarian tumors induced by DBPDHD was higher (60.7%), although not significantly, than that induced by DBP (44.8%). Similarly the levels of DNA damage induced by DBPDHD in the ovary were higher than those observed with DBP. We did not observe any histological abnormality in the ovary of mice treated with DBPDE, which is consistent with lack of DNA damage. Our results suggested that both DBP and DBPDHD can be metabolized in the mouse ovary leading to the formation of DBPDE that can damage DNA, which is a prerequisite step in the initiation stage of carcinogenesis.


Assuntos
Benzopirenos/toxicidade , Dano ao DNA/efeitos dos fármacos , Neoplasias Ovarianas/etiologia , Ovário/efeitos dos fármacos , Administração Tópica , Animais , Benzopirenos/metabolismo , Carcinógenos/metabolismo , Carcinógenos/toxicidade , Cromatografia Líquida de Alta Pressão , Adutos de DNA/análise , Feminino , Camundongos , Neoplasias Ovarianas/mortalidade , Neoplasias Ovarianas/veterinária , Ovário/patologia , Taxa de Sobrevida , Espectrometria de Massas em Tandem
14.
Arch Toxicol ; 92(10): 3061-3075, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30159663

RESUMO

Alongside the analysis of urinary metabolites which are traditional biomarkers of polycyclic aromatic hydrocarbons (PAH) exposure, the possibility of detecting PAH as well as their metabolites in hair has also recently been demonstrated. As the concentration of pollutants detected in hair is not impacted by short-term variations in exposure as can be observed with urine, it accurately represents an individual's average level of exposure, which is the most relevant information when investigating possible linkages with biological effects. In the current study, based on a rat model exposed to a mixture of PAHs for a 90-day period, the linkage between the PAH exposure level and the resulting concentration of their metabolites in hair was then investigated. The linkage between exposure levels and the concentrations of OH-PAH in hair collected at the end of the experiment were compared to those obtained using urinary concentration of OH-PAH collected from the same animals. Linear relationship between levels of exposure and the concentration of OH-PAH in the rats' hair (R2 0.722-0.965, p < 0.001) was observed for 28 OH-PAH out of the 54 investigated. The difference in PAH concentration between the different groups of exposure and the possibility to back determine the animals' level of exposure on the basis of PAH-metabolite concentrations in both hair and urine was also demonstrated. In addition to the strong linear relation observed between the doses of exposure and the levels of concentration of hydroxylated metabolites in hair (p < 0.001), the analysis of a subset of animals demonstrated a linkage between 3-OH-benzo[a]pyrene concentration levels in hair and the levels of B[a]P-DNA adduct formed (p < 0.05), thereby suggesting the potential of their analysis to predict genetic alteration.


Assuntos
Adutos de DNA/sangue , Exposição Ambiental/análise , Cabelo/química , Hidrocarbonetos Policíclicos Aromáticos/análise , Animais , Benzopirenos/análise , Relação Dose-Resposta a Droga , Poluentes Ambientais/análise , Feminino , Cabelo/efeitos dos fármacos , Hidrocarbonetos Policíclicos Aromáticos/administração & dosagem , Hidrocarbonetos Policíclicos Aromáticos/metabolismo , Hidrocarbonetos Policíclicos Aromáticos/urina , Ratos Long-Evans
15.
Macromol Rapid Commun ; 39(13): e1800214, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29806160

RESUMO

4,10-dibromoanthanthrone, a highly robust building block, is used to synthesize a bis(triarylamine) polymer. The polymer can be oxidized twice to form a polycationic macromolecule showing magnetic properties by electron paramagnetic resonance spectroscopy. In its dicationic state, the presence of isolated radicals is possible because of the interrupted conjugation between the diphenylamine with the anthanthrone core. The high steric hindrance prevents the planarity of the adjacent groups resulting in a polyradical cationic polymer. The oxidized polymer has a strong absorption in the near-infrared region along with reversible redox stages.


Assuntos
Benzopirenos/química , Cátions
16.
J Immunotoxicol ; 15(1): 31-40, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-29482396

RESUMO

Benzo[a]pyrene (BaP) can induce developmental and reproductive toxicity; however, the full scope of its immunotoxic effects remains unknown. This study aimed to assess effects of lactational exposure to low-dose BaP (comparable to human exposure) on potential allergic\non-allergic immune responses in murine offspring. Lactating C3H/HeJ dams were orally dosed with BaP at 0, 0.25, 5.0, or 100 pmol/animal/week) at post-natal days [PND] 1, 8, and 15. Five-weeks-old pups then received intratracheally ovalbumin (OVA) every 2 weeks for 6 weeks. Following the final exposure, mice were processed to permit analyses of bronchoalveolar lavage (BAL) fluid cell profiles as well as levels of lung inflammatory cytokines and chemokines, serum OVA-specific immunoglobulin, and mediastinal lymph node (MLN) cell activation/proliferation. In OVA-sensitized male offspring, lactational low-dose BaP exposure led to enhanced (albeit not significantly) macrophage, neutrophil, and eosinophil infiltration to, and increased T-helper (TH)-2 cytokine production in, the lungs. In females, BaP exposure, regardless of dose, led to slightly enhanced lung levels of macrophages and eosinophils, and of inflammatory molecules. Protein levels of interleukin (IL)-33 in the OVA + BaP (middle dose) group, and interferon (IFN)-γ in the OVA + BaP (low dose) group, were higher than that of the OVA (no BaP) group. Ex vivo studies showed lactational exposure to BaP partially induced activation of T-cells and antigen-presenting cells (APCs) in the MLN cells of both male and female offspring, with or without OVA sensitization. Further, IL-4 and IFNγ levels in MLN culture supernatants were elevated even without OVA-re-stimulation in OVA + BaP groups. In conclusion, lactational exposure to low-dose BaP appeared to exert slight effects on later allergic and non-allergic immune responses in offspring by facilitating development of modest TH2 responses and activating MLN cells. In addition, lactational exposures to BaP might give rise to gender differences in allergic/non-allergic immune responses of offspring.


Assuntos
Asma/imunologia , Benzopirenos/toxicidade , Poluentes Ambientais/efeitos adversos , Pulmão/imunologia , Exposição Materna/efeitos adversos , Pneumonia/imunologia , Células Th2/imunologia , Animais , Células Cultivadas , Fumar Cigarros , Citocinas/metabolismo , Feminino , Lactação , Ativação Linfocitária , Camundongos , Camundongos Endogâmicos C3H , Gravidez , Emissões de Veículos
17.
Sci Rep ; 8(1): 2476, 2018 02 06.
Artigo em Inglês | MEDLINE | ID: mdl-29410452

RESUMO

Cancer incidence appears to be higher amongst firefighters compared to the general population. Given that many cancers have an environmental component, their occupational exposure to products of carbon combustion such as polycyclic aromatic hydrocarbons (PAHs) is of concern. This is the first UK study identifying firefighters exposure to PAH carcinogens. Wipe samples were collected from skin (jaw, neck, hands), personal protective equipment of firefighters, and work environment (offices, fire stations and engines) in two UK Fire and Rescue Service Stations. Levels of 16 US Environmental Protection Agency (EPA) PAHs were quantified together with more potent carcinogens: 7,12-dimethylbenzo[a]anthracene, and 3-methylcholanthrene (3-MCA) (12 months post-initial testing). Cancer slope factors, used to estimate cancer risk, indicate a markedly elevated risk. PAH carcinogens including benzo[a]pyrene (B[a]P), 3-MCA, and 7,12-dimethylbenz[a]anthracene PAHs were determined on body surfaces (e.g., hands, throat), on PPE including helmets and clothing, and on work surfaces. The main exposure route would appear to be via skin absorption. These results suggest an urgent need to monitor exposures to firefighters in their occupational setting and conduct long-term follow-up regarding their health status.


Assuntos
Carcinógenos/toxicidade , Bombeiros , Neoplasias/epidemiologia , Doenças Profissionais/epidemiologia , Exposição Ocupacional/efeitos adversos , Hidrocarbonetos Policíclicos Aromáticos/toxicidade , 9,10-Dimetil-1,2-benzantraceno/isolamento & purificação , 9,10-Dimetil-1,2-benzantraceno/toxicidade , Benzopirenos/isolamento & purificação , Benzopirenos/toxicidade , Carcinógenos/isolamento & purificação , Monitoramento Ambiental , Humanos , Incidência , Metilcolantreno/isolamento & purificação , Metilcolantreno/toxicidade , Neoplasias/etiologia , Neoplasias/prevenção & controle , Doenças Profissionais/etiologia , Doenças Profissionais/prevenção & controle , Hidrocarbonetos Policíclicos Aromáticos/isolamento & purificação , Roupa de Proteção , Pele/química , Pele/efeitos dos fármacos , Absorção Cutânea , Reino Unido/epidemiologia
18.
Int J Hyg Environ Health ; 221(2): 334-346, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29373287

RESUMO

BACKGROUND: Millions of workers are exposed to polycyclic aromatic hydrocarbons (PAHs), a well-known family of carcinogens, but occupational exposure data about PAH mixture compositions are scarce. OBJECTIVES: To provide a detailed picture of airborne PAH exposures encountered in the French industrial landscape over the previous 20 years and to identify determinants driving exposures. METHODS: Results from 1643 airborne samples of 16 gaseous and particulate PAHs implemented into the Exporisq HAP database from 1995 to 2014 were used to describe exposure levels and aerosol chemical composition in many industries and activities. Compliance of benzo[a]pyrene (BaP) levels with several existing occupational exposure limits for long-term exposure was assessed. RESULTS: BaP levels were lower than those reported in the literature, but the level and composition of PAH mixtures were highly variable between and within industries. Numerous exposure determinants (e.g., product composition, type and temperature of process, ventilation and confinement) were assumed to explain these differences. The highest levels were found in industries using products derived from coal (aluminum, silicon, and coke production, manufacturing of carbon products and foundries), with mean BaP levels up to 23 times higher than the French recommended value of 150 ng/m3. Forty-seven percent of the occupational activities exceeded this value. Conversely, exposures resulting from petroleum-derived products were relatively low. CONCLUSIONS: As health effects depend on PAH levels but also on the composition of the mixture, exposure assessments must characterize the entire mixtures and record specific determinants to define homogeneous exposure groups and to accurately assess health risks.


Assuntos
Benzopirenos/análise , Bases de Dados Factuais , Monitoramento Ambiental , Exposição Ocupacional/análise , França , Medição de Risco
19.
Bioorg Chem ; 77: 136-143, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29353730

RESUMO

Adenosine receptor antagonists are under investigation as potential drug candidates for the treatment of certain cancers, neurological disorders, depression and potentially improve tumour immunotherapy. The benzo-γ-pyrone scaffold is well-known in medicinal chemistry with diverse pharmacological activities attributed to them, however, their therapeutic potential as adenosine receptor antagonists have not been investigated in detail. To expand on the structure-activity relationships, the present study explored the adenosine A1 and A2A receptor binding affinities of a selected series of benzo-γ-pyrone analogues. In vitro evaluation led to the identification of 5-hydroxy-2-(3-hydroxyphenyl)-4H-1-benzopyran-4-one with the best adenosine A2A receptor affinity among the test compounds and was found to be non-selective (A1Ki = 0.956 µM; A2AKi = 1.44 µM). Hydroxy substitution on ring A and/or B play a key role in modulating the binding affinity at adenosine A1 and A2A receptors. Adenosine A1 receptor affinity was increased to the nanomolar range with hydroxy substitution on C6 (ring A), while meta-hydroxy substitution on ring B governed adenosine A2A receptor affinity. The double bond between C2 and C3 of ring C as well as C2 phenyl substitution was shown to be imperative for both adenosine A1 and A2A receptor affinity. Selected benzo-γ-pyrone derivatives behaved as adenosine A1 receptor antagonists in the performed GTP shift assays. It may be concluded that benzo-γ-pyrone based derivatives are suitable leads for designing and identifying adenosine receptor antagonists as treatment of various disorders.


Assuntos
Benzopirenos/farmacologia , Receptor A1 de Adenosina/metabolismo , Receptor A2A de Adenosina/metabolismo , Animais , Benzopirenos/química , Relação Dose-Resposta a Droga , Estrutura Molecular , Ratos , Relação Estrutura-Atividade
20.
J Cell Biochem ; 119(8): 6492-6500, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29345337

RESUMO

In this study, we attempted to find out the underlying mechanism of Benzoapyrene and metastasis of lung cancer cells. We also did experiments to testify the connection between BaP and its potential target, TNF-α. Cell median lethal dose (IC50 ) of both cells was measured by crystal violet method. Quantitative real-time reverse transcription PCR (qRT-PCR) and Western blot were employed to detect the expression of TNF-α. Wound healing assay and transwell assay were utilized to testify the impacts of BaP and TNF-α on the metastasis of lung cancer cells. Cell death rate was elevated with the increase of BaP concentration. BaP increased the number of metastatic cells of lung cancer. The expressions of TNF-α pathway-associated protein (TNF-α, NF-kB [P65], Caspase3, and Caspase8) were enhanced by overexpressed BaP. TNF-α shRNA suppressed the positive effects of BaP on migration and invasion of lung cancer cells. Our study validated the positive effects of BaP on the metastasis of lung cancer cells. We also revealed the instrumental role of TNF-α in helping the development of lung cancer cells induced by BaP.


Assuntos
Benzopirenos/toxicidade , Movimento Celular/efeitos dos fármacos , Neoplasias Pulmonares/metabolismo , Células A549 , Humanos , Neoplasias Pulmonares/patologia , Invasividade Neoplásica , Proteínas de Neoplasias/metabolismo
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