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1.
Ecotoxicol Environ Saf ; 202: 110864, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32610224

RESUMO

An increasing amount of Fluoranthene (Fla) and Benz(a)anthracene (BaA) is being produced and used, eventually entering the soil sediments. The accumulation of Fla and BaA will cause poisoning to typical enzymes (α-Amylase) and organisms (Eisenia fetida) in soil. However, the studies about exploring and comparing the different effects of Fla, BaA and their joint effect at different levels are rarely reported. In this paper, the different effects of Fla, BaA and their mixed pollutant on α-Amylase were evaluated and compared at the molecular level, and the effect of Fla-BaA to the antioxidant system of earthworm (Eisenia fetida) was investigated from the aspects of concentration and exposure time at the animal level. The results showed that Fla-BaA had the greatest influence on the skeleton structure and the microenvironment of amino acid residue of α-Amylase compared to Fla and BaA, and in the mixed pollutant system, the joint effect mode was additive mode. The inhibitory effect of Fla-BaA on the activity of α-Amylase was also stronger than that of the system alone. The assays at the animal level showed that low concentrations (below 5 mg/kg) of Fla-BaA increased the activity of GSH-Px and SOD while high concentrations inhibited their activity. The POD that was activated throughout the experiment period suggested its key role in the earthworm antioxidant system. Changes in T-AOC and MDA showed that long-term and high-dose of Fla-BaA exposure inhibited the antioxidant capacity of Eisenia fetida, causing lipid peroxidation and damage to cells.


Assuntos
Benzo(a)Antracenos/toxicidade , Fluorenos/toxicidade , Poluentes do Solo/toxicidade , Animais , Antracenos , Antioxidantes/metabolismo , Poluentes Ambientais/metabolismo , Poluição Ambiental , Peroxidação de Lipídeos/efeitos dos fármacos , Oligoquetos/efeitos dos fármacos , Solo/química , Testes de Toxicidade
2.
Mutat Res ; 853: 503173, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32522345

RESUMO

The aryl hydrocarbon receptor (AhR) transcription factor is activated by polycyclic aromatic hydrocarbons (PAH) and other ligands. Activated AhR binds to dioxin responsive elements (DRE) and initiates transcription of target genes, including the gene encoding prostaglandin endoperoxide synthase 2 (PTGS-2), which is also activated by the transcription factor NF-ĸB. PTGS-2 catalyzes the conversion of arachidonic acid (AA) into prostaglandins, thromboxanes or isoprostanes. 15-F2t-Isoprostane (IsoP), regarded as a universal marker of lipid peroxidation, is also induced by PAH exposure. We investigated the processes associated with lipid peroxidation in human alveolar basal epithelial cells (A549) exposed for 4 h or 24 h to model PAH (benzo[a]pyrene, BaP; 3-nitrobenzanthrone, 3-NBA) and organic extracts from ambient air particulate matter (EOM), collected in two seasons in a polluted locality. Both EOM induced the expression of CYP1A1 and CYP1B1; 24 h treatment significantly reduced PTGS-2 expression. IsoP levels decreased after both exposure periods, while the concentration of AA was not affected. The effects induced by BaP were similar to EOM except for increased IsoP levels after 4 h exposure and elevated AA concentration after 24 h treatment. In contrast, 3-NBA treatment did not induce CYP expression, had a weak effect on PTGS-2 expression, and, similar to BaP, induced IsoP levels after 4 h exposure and AA levels after 24 h treatment. All tested compounds induced the activity of NF-ĸB after the longer exposure period. In summary, our data suggest that EOM, and partly BaP, reduce lipid peroxidation by a mechanism that involves AhR-dependent inhibition of PTGS-2 expression. The effect of 3-NBA on IsoP levels is probably mediated by a different mechanism independent of AhR activation.


Assuntos
Células Epiteliais Alveolares/efeitos dos fármacos , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Mutagênicos/toxicidade , Receptores de Hidrocarboneto Arílico/metabolismo , Células A549 , Benzo(a)Antracenos/toxicidade , Benzo(a)pireno/toxicidade , Linhagem Celular Tumoral , Ciclo-Oxigenase 1/metabolismo , Citocromo P-450 CYP1A1/metabolismo , Humanos , NF-kappa B/metabolismo , Material Particulado/toxicidade , Hidrocarbonetos Policíclicos Aromáticos/toxicidade
3.
Toxicol Lett ; 331: 75-81, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32434050

RESUMO

Fungi of the genus Alternaria infest many agricultural crops and produce numerous mycotoxins, of which altertoxin II (ATX II) is one of the most mutagenic metabolites. ATX II carries an epoxide group but the formation of DNA adducts has not been demonstrated to date. We report now that ATX II gives rise to two covalent adducts with guanine when incubated with DNA under cell-free conditions. These adducts were demonstrated by LC-high resolution MS after enzymatic degradation of the incubated DNA to deoxynucleosides. The major adduct results from the covalent binding of ATX II, presumably through the epoxide group, to guanine, whereas the minor guanine adduct is derived from the major one by the elimination of two equivalents of water. In addition, a third adduct was detected, formed through covalent binding of ATX II to cytosine followed by the loss of two equivalents of water. The direct DNA reactivity of ATX II may explain its high mutagenicity.


Assuntos
Benzo(a)Antracenos/toxicidade , Adutos de DNA/análise , DNA/química , Guanina/química , Mutagênicos/toxicidade , Alternaria/química , Animais , Benzo(a)Antracenos/isolamento & purificação , Cromatografia Líquida , DNA/isolamento & purificação , Masculino , Espectrometria de Massas , Salmão , Testículo
4.
Chemosphere ; 255: 126955, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32416390

RESUMO

Polycyclic aromatic hydrocarbons (PAHs) can induce skin toxicity. Although some investigations have been conducted to assess the skin toxicity of different PAHs, few comparisons using a series of PAHs with different ring numbers and arrangements have been done. We aimed to explore the skin absorption of 6 PAH compounds and their effect on cutaneous inflammation. In vitro skin permeation was rated by Franz cell with pig skin. Molecular docking was employed to compute the PAH interaction with stratum corneum (SC) lipids. Cultured keratinocytes were exposed to PAHs for analyzing cytotoxicity, cyclooxygenase (COX)-2, prostaglandin E2 (PGE2), chemokines, and differentiation proteins. The in vivo topical PAH exposure in mice was characterized by skin absorption, transepidermal water loss (TEWL), PGE2 level, and histology. The skin deposition from the aqueous vehicle increased following the increase of PAH lipophilicity and molecular size, with benzo[a]pyrene (5-ring PAH) showing the greatest absorption. Pyrene was the compound showing the highest penetration across the skin (flux). Although the PAHs fluoranthene, pyrene, chrysene, and 1,2-benzanthracene all had 4 rings, the skin permeation was quite different. 1,2-Benzanthracene showed the greatest absorption among the 4-ring compounds. The PAHs with higher absorption exhibited stronger interaction with SC lipids according to the in silico modeling. Chrysene and 1,2-benzanthracene generally showed the highest COX-2 and PGE2 expression, followed by benzo[a]pyrene. The lowest COX-2 and PGE2 upregulation was observed for naphthalene (2-ring PAH). A contrary tendency was detected for the upregulation of chemokines. Filaggrin and integrin ß1 in keratinocytes were suppressed at a comparable level by all PAHs. The skin's absorption of PAHs showed strong in vivo-in vitro correlation. 1,2-Benzanthracene and benzo[a]pyrene highly disrupted the skin barrier and elevated the inflammation in vivo. The tendency toward in vivo inflammation caused by various PAHs could be well predicted by the combined estimation using in vitro skin absorption and a keratinocyte bioassay. This study also established the structure-permeation relationship (SPR) of PAHs.


Assuntos
Hidrocarbonetos Policíclicos Aromáticos/metabolismo , Absorção Cutânea , Pele/metabolismo , Animais , Benzo(a)Antracenos , Benzo(a)pireno/toxicidade , Crisenos , Inflamação/metabolismo , Queratinócitos , Camundongos , Simulação de Acoplamento Molecular , Naftalenos , Hidrocarbonetos Policíclicos Aromáticos/toxicidade , Pirenos , Suínos
5.
Chemosphere ; 249: 126097, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32078851

RESUMO

Benz(a)anthracene (BaA) is a polycyclic aromatic hydrocarbons (PAHs), that belongs to a group of carcinogenic and mutagenic persistent organic pollutants found in a variety of ecological habitats. In this study, the efficient biodegradation of BaA by a green alga Chlamydomonas reinhardtii (C. reinhardtii) CC-503 was investigated. The results showed that the growth of C. reinhardtii was hardly affected with an initial concentration of 10 mg/L, but was inhibited significantly under higher concentrations of BaA (>30 mg/L) (p < 0.05). We demonstrated that the relatively high concentration of 10 mg/L BaA was degraded completely in 11 days, which indicated that C. reinhardtii had an efficient degradation system. During the degradation, the intermediate metabolites were determined to be isomeric phenanthrene or anthracene, 2,6-diisopropylnaphthalene, 1,3-diisopropylnaphthalene, 1,7-diisopropylnaphthalene, and cyclohexanol. The enzymes involved in the degradation included the homogentisate 1,2-dioxygenase (HGD), the carboxymethylenebutenolidase, the ribulose 1,5-bisphosphate carboxylase/oxygenase (Rubisco) and the ubiquinol oxidase. The respective genes encoding these proteins were significantly up-regulated ranging from 3.17 fold to 13.03 fold and the activity of enzymes, such as HGD and Rubisco, was significantly induced up to 4.53 and 1.46 fold (p < 0.05), during the BaA metabolism. This efficient degradation ability suggests that the green alga C. reinhardtii CC-503 may be a sustainable candidate for PAHs remediation.


Assuntos
Antracenos/metabolismo , Biodegradação Ambiental , Chlamydomonas reinhardtii/metabolismo , Poluentes Ambientais/metabolismo , Benzo(a)Antracenos/metabolismo , Carcinógenos/metabolismo , Dioxigenases/metabolismo , Fenantrenos , Hidrocarbonetos Policíclicos Aromáticos/metabolismo
6.
Sci Rep ; 10(1): 3465, 2020 02 26.
Artigo em Inglês | MEDLINE | ID: mdl-32103055

RESUMO

In this work we report the occurrence of powerful mutagenic 3-nitrobenzanthrone (3-NBA), in addition to 18 polycyclic aromatic hydrocarbons (PAHs), 6 oxygenated PAHs and 27 nitrated PAHs in polychaete worms. Benzanthrone (BA), another important mutagenic polycyclic aromatic compound (PAC) also was detected in the samples. Polychaete annelids have great ecological relevance, being widely distributed in different environmental conditions, from intertidal zones up to seven thousand feet deep areas. They are abundantly found in both contaminated and uncontaminated areas and, therefore, used as indicators of the pollution status of a given area. As we know, so far, most of these PACs has not been previously reported in living organisms before. The 3-NBA concentrations determined in this study were within 0.11-5.18 µg g-1. Other relevant PACs such as PAHs, quinones and nitro-PAHs were found in maximum concentrations at 0.013 µg g-1 (coronene) to 11.1 µg g-1 (benzo[k]fluoranthene), 0.823 µg g-1 (9,10-phenenthrenequinone) to 12.1 µg g-1 (1,4-benzoquinone) and 0.434 (1-nitronaphthalene) µg g-1 to 19.2 µg g-1 (6-nitrobenzo[a]pyrene), respectively. Principal component analysis (PCA), ternary correlations and diagnostic ratios were employed in order to propose probable sources for PACs. Although statistical analysis preliminarily has indicated both pyrogenic and petrogenic contributions, petrogenic sources were predominant reflecting the impacts of petroleum exploration and intensive traffic of boats in the study area.


Assuntos
Benzo(a)Antracenos/análise , Mutagênicos/análise , Poliquetos/química , Hidrocarbonetos Policíclicos Aromáticos/análise , Animais , Benzo(a)Antracenos/isolamento & purificação , Benzo(a)Antracenos/metabolismo , Monitoramento Ambiental , Cromatografia Gasosa-Espectrometria de Massas , Limite de Detecção , Mutagênicos/metabolismo , Poliquetos/metabolismo , Hidrocarbonetos Policíclicos Aromáticos/isolamento & purificação , Hidrocarbonetos Policíclicos Aromáticos/metabolismo , Análise de Componente Principal , Extração em Fase Sólida/métodos , Sonicação , Poluentes Químicos da Água/análise , Poluentes Químicos da Água/isolamento & purificação , Poluentes Químicos da Água/metabolismo
7.
Chem Res Toxicol ; 32(12): 2538-2551, 2019 12 16.
Artigo em Inglês | MEDLINE | ID: mdl-31746589

RESUMO

3-Nitrobenzanthrone (3-NBA) is a suspected human carcinogen present in diesel exhaust. It requires metabolic activation via nitroreduction in order to form DNA adducts and promote mutagenesis. We have determined that human aldo-keto reductases (AKR1C1-1C3) and NAD(P)H:quinone oxidoreductase 1 (NQO1) contribute equally to the nitroreduction of 3-NBA in lung epithelial cell lines and collectively represent 50% of the nitroreductase activity. The genes encoding these enzymes are induced by the transcription factor NF-E2 p45-related factor 2 (NRF2), which raises the possibility that NRF2 activation exacerbates 3-NBA toxification. Since A549 cells possess constitutively active NRF2, we examined the effect of heterozygous (NRF2-Het) and homozygous NRF2 knockout (NRF2-KO) by CRISPR-Cas9 gene editing on the activation of 3-NBA. To evaluate whether NRF2-mediated gene induction increases 3-NBA activation, we examined the effects of NRF2 activators in immortalized human bronchial epithelial cells (HBEC3-KT). Changes in AKR1C1-1C3 and NQO1 expression by NRF2 knockout or use of NRF2 activators were confirmed by qPCR, immunoblots, and enzyme activity assays. We observed decreases in 3-NBA activation in the A549 NRF2 KO cell lines (53% reduction in A549 NRF2-Het cells and 82% reduction in A549 NRF2-KO cells) and 40-60% increases in 3-NBA bioactivation due to NRF2 activators in HBEC3-KT cells. Together, our data suggest that activation of the transcription factor NRF2 exacerbates carcinogen metabolism following exposure to diesel exhaust which may lead to an increase in 3-NBA-derived DNA adducts.


Assuntos
Poluentes Atmosféricos/toxicidade , Benzo(a)Antracenos/toxicidade , Regulação da Expressão Gênica/fisiologia , Mutagênicos/toxicidade , Fator 2 Relacionado a NF-E2/metabolismo , 20-Hidroxiesteroide Desidrogenases/genética , Células A549 , Ativação Metabólica , Poluentes Atmosféricos/metabolismo , Membro C3 da Família 1 de alfa-Ceto Redutase/genética , Benzo(a)Antracenos/metabolismo , Brônquios/citologia , Células Epiteliais/efeitos dos fármacos , Técnicas de Inativação de Genes , Humanos , Hidroxiesteroide Desidrogenases/genética , Imidazóis/farmacologia , Isotiocianatos/farmacologia , Mutagênicos/metabolismo , NAD(P)H Desidrogenase (Quinona)/genética , Fator 2 Relacionado a NF-E2/agonistas , Fator 2 Relacionado a NF-E2/genética , Ácido Oleanólico/análogos & derivados , Ácido Oleanólico/farmacologia , Estresse Oxidativo/efeitos dos fármacos , RNA Mensageiro/genética , RNA Mensageiro/metabolismo
8.
Arch Toxicol ; 93(11): 3153-3167, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31641809

RESUMO

Despite the frequent infection of agricultural crops by Alternaria spp., their toxic secondary metabolites and potential food contaminants lack comprehensive metabolic characterization. In this study, we investigated their bioavailability, metabolism, and excretion in vivo. A complex Alternaria culture extract (50 mg/kg body weight) containing 11 known toxins and the isolated lead toxin altertoxin II (0.7 mg/kg body weight) were administered per gavage to groups of 14 Sprague Dawley rats each. After 3 h and 24 h, plasma, urine and feces were collected to determine toxin recoveries. For reliable quantitation, an LC-MS/MS method for the simultaneous detection of 20 Alternaria toxins and metabolites was developed and optimized for either biological matrix. The obtained results demonstrated efficient excretion of alternariol (AOH) and its monomethyl ether (AME) via feces (> 89%) and urine (> 2.6%) after 24 h, while the majority of tenuazonic acid was recovered in urine (20 and 87% after 3 and 24 h, respectively). Moreover, modified forms of AOH and AME were identified in urine and fecal samples confirming both, mammalian phase-I (4-hydroxy-AOH) and phase-II (sulfates) biotransformation in vivo. Despite the comparably high doses, perylene quinones were recovered only at very low levels (altertoxin I, alterperylenol, < 0.06% in urine and plasma, < 5% in feces) or not at all (highly genotoxic, epoxide-holding altertoxin II, stemphyltoxin III). Interestingly, altertoxin I was detected in all matrices of rats receiving altertoxin II and suggests enzymatic de-epoxidation in vivo. In conclusion, the present study contributes valuable information to advance our understanding of the emerging Alternaria mycotoxins and their relevance on food safety.


Assuntos
Alternaria/química , Benzo(a)Antracenos/metabolismo , Micotoxinas/metabolismo , Alternaria/crescimento & desenvolvimento , Animais , Benzo(a)Antracenos/sangue , Benzo(a)Antracenos/isolamento & purificação , Benzo(a)Antracenos/urina , Disponibilidade Biológica , Temperatura Corporal/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Cromatografia Líquida , Ingestão de Alimentos/efeitos dos fármacos , Fezes/química , Contaminação de Alimentos/análise , Limite de Detecção , Masculino , Taxa de Depuração Metabólica , Desentoxicação Metabólica Fase I , Desintoxicação Metabólica Fase II , Micotoxinas/sangue , Micotoxinas/isolamento & purificação , Micotoxinas/urina , Ratos Sprague-Dawley , Espectrometria de Massas em Tandem , Distribuição Tecidual
9.
Artigo em Chinês | MEDLINE | ID: mdl-31495125

RESUMO

Objective: To investigate the characteristics of occupational exposure to polycyclic aromatic hydrocarbons (PAHs) in the workplace and for various types of work in a carbon enterprise based on the measurement data of various components of PAHs in the air from the workplace of the carbon enterprise, and to provide a scientific basis for protection against PAHs in this enterprise. Methods: In July 2017, a carbon enterprise in Shandong Province and its on-duty workers were chosen as subjects. On-site occupational hygiene investigation and high-performance liquid chromatography were used to investigate and determine the presence and concentrations of PAHs in various workshops and various types of work in the enterprise, and toxic equivalent quantity (TEQ) was used to evaluate the carcinogenic level of PAHs. Results: The components of PAHs with relatively high content in the air of the workplace in the carbon enterprise were fluoranthene, pyrene, benzanthracene, X, and benzo[a]pyrene, with mean concentrations of 1 485.66, 864.66, 805.35, 500.08, and 120.88 ng/m(3), respectively. There were significant differences between the three workshops in the concentrations of PAHs components (benzo[a]pyrene, benzanthracene, benzo[b]fluoranthene, benzo[k]fluoranthene, X, fluoranthene, pyrene, fluorene, indenopyrene, and anthracene) and total TEQ (P<0.05) . The total TEQ of PAHs in the molding workshop was significantly higher than that in other workshops (P<0.05) . There were significant differences between different types of work in the exposure to pyrene and fluoranthene and TEQ (P<0.05) . Shaking-table operators, moving-sieve operators, batching operators, fabric workers, and hot-oil stove workers had higher exposure levels of PAHs. The exposure concentrations of benzo[a]pyrene and benzanthracene were highly correlated with total TEQ. Conclusion: The concentration of PAHs in the working environment of the carbon enterprise is generally higher; benzo[a]pyrene and fluoranthene are the PAHs components against which special protective measures need to be taken; molding workshops are the workshops that are most seriously endangered by PAHs; shaking-table operators are the type of workers needing special protection against PAHs. The occupational hazards of PAHs in the carbon industry cannot be ignored, against which corresponding protective measures should be formulated based on their exposure characteristics.


Assuntos
Carcinógenos/análise , Exposição Ocupacional/análise , Hidrocarbonetos Policíclicos Aromáticos/análise , Benzo(a)Antracenos/análise , Benzo(a)pireno/análise , Carbono , Cromatografia Líquida de Alta Pressão , Humanos , Saúde do Trabalhador
10.
Chem Res Toxicol ; 32(8): 1699-1706, 2019 08 19.
Artigo em Inglês | MEDLINE | ID: mdl-31286773

RESUMO

3-Nitrobenzanthrone (3-NBA) is a byproduct of diesel exhaust and is highly present in industrial and populated areas. Inhalation of 3-NBA results in formation of N-(2'-deoxyguanosin-8-yl)-3-aminobenzanthrone (dGC8-N-ABA), a bulky DNA lesion that is of concern due to its mutagenic and carcinogenic potential. If dGC8-N-ABA is not bypassed during genomic replication, the lesion can stall cellular DNA replication machinery, leading to senescence or apoptosis. We have previously used running start assays to demonstrate that human DNA polymerases eta (hPolη) and kappa (hPolκ) are able to catalyze translesion DNA synthesis (TLS) across a site-specifically placed dGC8-N-ABA in a DNA template. Consistently, gene knockdown of hPolη and hPolκ in HEK293T cells reduces the efficiency of TLS across dGC8-N-ABA by ∼25 and ∼30%, respectively. Here, we kinetically investigated why hPolκ paused when bypassing and extending from dGC8-N-ABA. Our kinetic data show that correct dCTP incorporation efficiency of hPolκ dropped by 116-fold when opposite dGC8-N-ABA relative to undamaged dG, leading to hPolκ pausing at the lesion site observed in the running start assays. The already low nucleotide incorporation fidelity of hPolκ was further decreased by 10-fold during lesion bypass, and thus, incorrect nucleotides, especially dATP, were incorporated opposite dGC8-N-ABA with comparable efficiencies as correct dCTP. With regard to the dGC8-N-ABA bypass product extension step, hPolκ incorporated correct dGTP onto the damaged DNA substrate with a 786-fold lower efficiency than onto the corresponding undamaged DNA substrate, which resulted in hPolκ pausing at the site in the running start assays. Furthermore, hPolκ extended the primer-terminal matched base pair dC:dGC8-N-ABA with a 100-1000-fold lower fidelity than it extended the undamaged dC:dG base pair. Together, our kinetic results strongly indicate that hPolκ was error-prone during TLS of dGC8-N-ABA.


Assuntos
Benzo(a)Antracenos/metabolismo , Biocatálise , DNA Polimerase Dirigida por DNA/metabolismo , Benzo(a)Antracenos/química , Dano ao DNA , Replicação do DNA , DNA Polimerase Dirigida por DNA/deficiência , DNA Polimerase Dirigida por DNA/genética , Células HEK293 , Humanos , Cinética , Modelos Moleculares , Estrutura Molecular
11.
Environ Monit Assess ; 191(7): 417, 2019 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-31172293

RESUMO

Ingestion of leafy vegetables is an important dietary component of most Africans due to its health benefits. High levels of polycyclic aromatic hydrocarbons (PAHs) in the leafy vegetables may pose a significant health hazard to the consumers. Rose/Hibiscus, Chinese cabbage, lettuce, and garden egg leaves from farms along the Nima Creek, Accra, were selected. At each sampling site, the vegetable was uprooted and cut into leaves, stem, and root and analyzed differently. The GC-MS method was employed in the identification and quantification of 16 PAHs in the samples. The analysis was done at CSIR - Water Research Institute Organic Laboratory. The results obtained show concentrations of acenapththylene, acenapthene, benzo[a]anthracene, benzo[b]fluoranthene, and benzo[a]pyrene (except chrysene and pyrene which were found in garden egg leaves and Chinese cabbage respectively), while naphthalene was detected in all the vegetables. The mean concentration of phenanthrene in leaves, stem, and roots of Chinese cabbage vegetable varies according to the following order: roots (0.744 ± 0.16 µg/kg) ≥ leaves (0.598 ± 1.21 µg/kg) ≥ stem (0.327 ± 1.01 µg/kg). From the results of the isomeric ratios, the source of the PAHs in the leafy vegetables are from mixed sources, i.e., either pyrogenic and petrogenic origins. This calls for the formulation of stringent policies on the importation of over-age vehicles into the countries as well as on the indiscriminate burning of materials containing PAHs.


Assuntos
Brassica/química , Monitoramento Ambiental/métodos , Hibiscus/química , Alface/química , Hidrocarbonetos Policíclicos Aromáticos/análise , Verduras/química , Acenaftenos/análise , Benzo(a)Antracenos/análise , Benzo(a)pireno/análise , Dieta , Fazendas , Fluorenos/análise , Inocuidade dos Alimentos , Cromatografia Gasosa-Espectrometria de Massas , Gana , Naftalenos/análise , Fenantrenos/análise
12.
Mol Med Rep ; 19(5): 4326-4334, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30942392

RESUMO

Long­term exposure to vehicle exhaust gas may lead to various age­associated disorders, including cardiovascular disease and cancer. Polycyclic aromatic hydrocarbons (PAHs) belong to an important class of carcinogens, which are released into the environment by vehicles and are detectable at high levels in Chinese urban areas. However, whether vehicle exhaust gas (EG), and in particular the PAHs derived from EG, are able to induce cell senescence remains unclear. In the present study, vehicle EG and pure PAHs were used as pollution sources to investigate the effects of long­term exposure to PAH on the cellular processes occurring in mouse lung fibroblast cells (mLFCs). Using cell proliferation and apoptosis assays, it was demonstrated that benzopyrene (BaP) suppressed the proliferation of mLFCs, and benzanthracene (BaA) and BaP induced cell apoptosis. Molecular analysis suggested that long­term exposure to BaA and BaP was able to increase the protein expression levels of p53, p21 and the apoptotic factors involved in the caspase cascade, including caspase­3 and ­9. Notably, the present study suggested that PAH exposure was able to promote cell senescence in mLFCs by activating the ATM serine/threonine kinase/H2A histone family member X pathway. The present study may provide novel insights into the underlying mechanism of vehicle EG and PAHs in promoting the development of age­associated diseases.


Assuntos
Senescência Celular/efeitos dos fármacos , Hidrocarbonetos Policíclicos Aromáticos/toxicidade , Poluentes Atmosféricos/toxicidade , Animais , Apoptose/efeitos dos fármacos , Benzo(a)Antracenos/toxicidade , Caspase 3/metabolismo , Células Cultivadas , Inibidor p16 de Quinase Dependente de Ciclina/genética , Inibidor p16 de Quinase Dependente de Ciclina/metabolismo , Metilação de DNA , Feminino , Fibroblastos/citologia , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Pulmão/citologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Regiões Promotoras Genéticas , Proteína Supressora de Tumor p53/metabolismo , Emissões de Veículos
13.
Lett Appl Microbiol ; 68(6): 589-596, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30942912

RESUMO

Industrialization often causes polycyclic aromatic hydrocarbon (PAH) and heavy metal contamination of soil and water. In this study, we isolated a bacterium from bottom mud water around a park of Kawasaki Port, Japan, that degrades the 5-ring PAH dibenz[a,h]anthracene (DBA). The strain, Comamonas sp. 3ah48, degraded 29% of DBA (30 µg ml-1 ) in 7 days, and the degradation level increased drastically, to 59%, by the addition of glutamate to the medium. The strain also degraded 40, 14, 15 and 19% of pyrene (Pyr), benzo[b]fluoranthene (BbF), benzo[k]fluoranthene (BkF) and benzo[g,h,i]perylene (BghiP) respectively. Benzo[a]pyrene (BaP) was degraded only when glutamate was added to the medium. Strain 3ah48 retained its degradation levels in the presence of 2 mmol l-1 Co2+ , Zn2+ or Cr2+ , at almost the same level as that without metal, and increased the DBA degradation level to 57% in the presence of 2 mmol l-1 Cu2+ , suggesting the possibility of the presence of laccase. SIGNIFICANCE AND IMPACT OF THE STUDY: Sixteen polycyclic aromatic hydrocarbons (PAHs) are listed as priority pollutants by the United States Environmental Protection Agency (USEPA). Information about the biodegradation of one of those PAHs, dibenz[a,h]anthracene (DBA), is limited. The present study focuses on DBA degradation by Comamonas sp. 3ah48 strain isolated around Kawasaki Port, Japan. Comamonas sp. 3ah48, cultured with the addition of glutamate to the medium, was found to increase the degradation level of DBA and to degrade DBA even in the presence of high concentrations of heavy metals.


Assuntos
Benzo(a)Antracenos/metabolismo , Benzo(a)pireno/metabolismo , Biodegradação Ambiental , Comamonas/metabolismo , Metais Pesados/toxicidade , Comamonas/efeitos dos fármacos , Sedimentos Geológicos/microbiologia , Ácido Glutâmico/metabolismo , Japão , Hidrocarbonetos Policíclicos Aromáticos/metabolismo , Solo/química , Microbiologia do Solo
14.
Molecules ; 24(6)2019 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-30884744

RESUMO

The formation of polycyclic aromatic hydrocarbons (PAHs) is a strong global concern due to their harmful effects. To help the reduction of their emissions, a crucial understanding of their formation and a deep exploration of their growth mechanism is required. In the present work, the formation of benzo(a)pyrene was investigated computationally employing chrysene and benz(a)anthracene as starting materials. It was assumed a type of methyl addition/cyclization (MAC) was the valid growth mechanism in this case. Consequently, the reactions implied addition reactions, ring closures, hydrogen abstractions and intramolecular hydrogen shifts. These steps of the mechanism were computed to explore benzo(a)pyene formation. The corresponding energies of the chemical species were determined via hybrid density funcional theory (DFT), B3LYP/6-31+G(d,p) and M06-2X/6-311++G(d,p). Results showed that the two reaction routes had very similar trends energetically, the difference between the energy levels of the corresponding molecules was just 6.13 kJ/mol on average. The most stable structure was obtained in the benzo(a)anthracene pathway.


Assuntos
Benzo(a)Antracenos/química , Benzo(a)pireno/química , Carcinógenos/química , Hidrocarbonetos Policíclicos Aromáticos/química , Benzo(a)Antracenos/toxicidade , Benzo(a)pireno/toxicidade , Carcinógenos/toxicidade , Crisenos/química , Humanos , Hidrogênio/química , Estrutura Molecular , Hidrocarbonetos Policíclicos Aromáticos/toxicidade
15.
Mutagenesis ; 34(2): 153-164, 2019 05 29.
Artigo em Inglês | MEDLINE | ID: mdl-30852615

RESUMO

Polycyclic aromatic hydrocarbons (PAHs) may cause lipid peroxidation via reactive oxygen species generation. 15-F2t-isoprostane (IsoP), an oxidative stress marker, is formed from arachidonic acid (AA) by a free-radical induced oxidation. AA may also be converted to prostaglandins (PG) by prostaglandin-endoperoxide synthase (PTGS) induced by NF-κB. We treated human embryonic lung fibroblasts (HEL12469) with benzo[a]pyrene (B[a]P), 3-nitrobenzanthrone (3-NBA) and extractable organic matter (EOM) from ambient air particulate matter <2.5 µm for 4 and 24 h. B[a]P and 3-NBA induced expression of PAH metabolising, but not antioxidant enzymes. The concentrations of IsoP decreased, whereas the levels of AA tended to increase. Although the activity of NF-κB was not detected, the tested compounds affected the expression of prostaglandin-endoperoxide synthase 2 (PTGS2). The levels of prostaglandin E2 (PGE2) decreased following exposure to B[a]P, whereas 3-NBA exposure tended to increase PGE2 concentration. A distinct response was observed after EOM exposure: expression of PAH-metabolising enzymes was induced, IsoP levels increased after 24-h treatment but AA concentration was not affected. The activity of NF-κB increased after both exposure periods, and a significant induction of PTGS2 expression was found following 4-h treatment. Similarly to PAHs, the EOM exposure was associated with a decrease of PGE2 levels. In summary, exposure to PAHs with low pro-oxidant potential results in a decrease of IsoP levels implying 'antioxidant' properties. For such compounds, IsoP may not be a suitable marker of lipid peroxidation.


Assuntos
Peroxidação de Lipídeos/efeitos dos fármacos , Pulmão/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Material Particulado/toxicidade , Hidrocarbonetos Policíclicos Aromáticos/toxicidade , Poluentes Atmosféricos/toxicidade , Ácido Araquidônico/metabolismo , Hidrocarboneto de Aril Hidroxilases/metabolismo , Benzo(a)Antracenos/toxicidade , Benzo(a)pireno/toxicidade , Células Cultivadas , Ciclo-Oxigenase 2/metabolismo , Dinoprosta/análogos & derivados , Dinoprosta/biossíntese , Dinoprosta/metabolismo , Dinoprostona/biossíntese , Dinoprostona/metabolismo , Fibroblastos/efeitos dos fármacos , Fibroblastos/enzimologia , Humanos , Pulmão/citologia , Pulmão/embriologia , Pulmão/enzimologia , NF-kappa B/metabolismo , Espécies Reativas de Oxigênio/metabolismo
16.
Luminescence ; 34(3): 353-359, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30784170

RESUMO

In the present study a new luminescent dye 3-N-(2-pyrrolidinylacetamido)benzanthrone (AZR) was synthesized. Spectroscopic measurements of the novel benzanthrone 3-aminoderivative were performed in seven organic solvents showing strong fluorescence. The capability of the prepared dye for visualization has been tested on flax, red clover and alfalfa to determinate the embryo in plant callus tissue cultures. Callus cells were stained with AZR and further analysed utilizing confocal laser scanning fluorescence microscopy. Performed experiments show high visualization effectiveness of newly synthesized fluorescent dye AZR that is efficient in fast and relatively inexpensive diagnostics of callus embryos that are problematic due to in vitro culture specificity.


Assuntos
Benzo(a)Antracenos/química , Linho/química , Linho/embriologia , Corantes Fluorescentes/química , Medicago sativa/química , Medicago sativa/embriologia , Microscopia Confocal/métodos , Trifolium/química , Trifolium/embriologia , Fluorescência , Técnicas de Cultura de Tecidos
17.
Toxicol Lett ; 301: 168-178, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30321595

RESUMO

Alternaria mycotoxins frequently contaminate agricultural crops and may impact animal and human health. However, data on mammalian metabolism and potential biomarkers of exposure for human biomonitoring (HBM) are scarce. Here, we report the preliminary investigation with respect to metabolism and excretion of Alternaria toxins in Sprague Dawley rats. Four animals were housed in metabolic cages for 24 h after gavage administration of an Alternaria alternata culture extract containing ten known toxins. LC-MS/MS analysis of 17 Alternaria toxins in urine and fecal samples allowed to gain first insights regarding xenobiotic metabolism and excretion rates. Alternariol (6-10%), alternariol monomethyl ether (AME, 6-7%) and tenuazonic acid (up to 55%) were recovered in urine and fecal samples (9%, 87%, 0.3%, respectively), while perylene quinones administered at comparatively high levels, were either determined at very low levels (up to 0.5% altertoxin I in urine and 15% in feces; 0.2% alterperylenol in urine and 3% in feces) or not at all (altertoxin II, stemphyltoxin III). AME-3-sulfate, which was not present in the administered extract, was determined in urine, representing up to 23% of the AME intake. Critical evaluation of the applied sample preparation protocol and LC-MS/MS analysis revealed interesting preliminary results and information crucial for improving follow-up experiments.


Assuntos
Alternaria , Micotoxinas/metabolismo , Animais , Benzo(a)Antracenos/metabolismo , Benzo(a)Antracenos/urina , Cromatografia Líquida , Fezes/química , Lactonas/metabolismo , Lactonas/urina , Limite de Detecção , Masculino , Micotoxinas/urina , Perileno/análogos & derivados , Perileno/metabolismo , Perileno/urina , Ratos , Ratos Sprague-Dawley , Espectrometria de Massas em Tandem , Ácido Tenuazônico/metabolismo , Ácido Tenuazônico/urina
18.
J Hazard Mater ; 365: 322-330, 2019 03 05.
Artigo em Inglês | MEDLINE | ID: mdl-30447640

RESUMO

The biodegradation of benz[α]anthracene (BaA), which was a high-molecule-weight PAH, was enhanced via a combination of alkaline and alkyl polyglucosides (APG) treatment during waste activated sludge (WAS) anaerobic fermentation. The biodegradation efficiency of BaA was increased from 14.1% in the control to 30.2 and 47.8% in pH 10 and pH 10 & APG reactors, respectively. Mechanism investigations found that the alkaline and APG treatments stimulated the processes of BaA desorption from sludge and transfer/entry into microorganisms, and ultimately improved the BaA bioavailability. Meanwhile, the huge released substrates from WAS not only served as carbon sources but also involved in the electron transfer among microorganisms which contributed to the BaA biodegradation process. Moreover, the microbial activities involved in BaA biodegradation, including the abundances of functional bacteria, activities of enzymes and quantities of genes, were also incremented due to the alkaline and APG treatments. Overall, the simultaneous improvement of BaA bioavailability and microbial activities enhanced its biodegradation efficiency.


Assuntos
Bacteroidetes/metabolismo , Benzo(a)Antracenos/metabolismo , Glucosídeos/farmacologia , Propionibacteriaceae/metabolismo , Poluentes Químicos da Água/metabolismo , Anaerobiose , Biodegradação Ambiental , Disponibilidade Biológica , Concentração de Íons de Hidrogênio
19.
Molecules ; 23(12)2018 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-30558365

RESUMO

Intramolecular photocyclization of stilbene derivatives (Mallory reaction) is one of the efficient methods for building polycyclic aromatic hydrocarbon (PAH) frameworks, and is also expected to be applicable to synthesis of fluorine-containing PAHs (F-PAHs). In this study, dibenzoanthracene-type (4a) and benzoperylene-type (4b) F-PAHs were synthesized using the Mallory reaction of the 1,4-distyrylbenzene-type π-conjugated molecule (3a), which was prepared by addition-defluorination of available octafluorocyclopentene (OFCP) and aryllithium in three steps. The structure of 4a originating from π⁻π interaction was characterized by X-ray crystallographic analysis. The absorption maxima of UV-Vis spectra and emission maxima of photoluminescence spectra of the PAHs were positioned at a longer wavelength compared to those of the corresponding unsubstituted PAHs, presumably due to the electron-withdrawing nature of perfluorocyclopentene (PFCP) units. The effect of PFCP units in F-PAHs was also studied by time-dependent density functional theory (TD-DFT) calculation.


Assuntos
Benzo(a)Antracenos/química , Benzo(a)Antracenos/síntese química , Flúor/química , Perileno/análogos & derivados , Hidrocarbonetos Policíclicos Aromáticos/química , Hidrocarbonetos Policíclicos Aromáticos/síntese química , Modelos Moleculares , Perileno/síntese química , Perileno/química , Espectrofotometria Ultravioleta
20.
Chem Res Toxicol ; 31(11): 1277-1288, 2018 11 19.
Artigo em Inglês | MEDLINE | ID: mdl-30406992

RESUMO

3-Nitrobenzanthrone (3-NBA) is a potent mutagen and suspected human carcinogen detected in diesel exhaust particulate and ambient air pollution. It requires metabolic activation via nitroreduction to promote DNA adduct formation and tumorigenesis. NAD(P)H:quinone oxidoreductase 1 (NQO1) has been previously implicated as the major nitroreductase responsible for 3-NBA activation, but it has recently been reported that human aldo-keto reductase 1C3 (AKR1C3) displays nitroreductase activity toward the chemotherapeutic agent PR-104A. We sought to determine whether AKR1C isoforms could display nitroreductase activity toward other nitrated compounds and bioactivate 3-NBA. Using discontinuous enzymatic assays monitored by UV-HPLC, we determined that AKR1C1-1C3 catalyze three successive two-electron nitroreductions toward 3-NBA to form the reduced product 3-aminobenzanthrone (3-ABA). Evidence of the nitroso- and hydroxylamino- intermediates were obtained by UPLC-HRMS. Km, kcat, and kcat/ Km values were determined for recombinant AKR1C and NQO1 and compared. We found that AKR1C1, AKR1C3, and NQO1 have very similar apparent catalytic efficiencies (8 vs 7 min-1 mM-1) despite the higher kcat of NQO1 (0.058 vs 0.012 min-1). AKR1C1-1C3 possess a Km much lower than that of NQO1, which suggests that they may be more important than NQO1 at the low concentrations of 3-NBA to which humans are exposed. Given that inhalation represents the primary source of 3-NBA exposure, we chose to evaluate the relative importance of AKR1C1-1C3 and NQO1 in human lung epithelial cell lines. Our data suggest that the combined activities of AKR1C1-1C3 and NQO1 contribute equally to the reduction of 3-NBA in A549 and HBEC3-KT cell lines and together represent approximately 50% of the intracellular nitroreductase activity toward 3-NBA. These findings have significant implications for the metabolism of nitrated polycyclic aromatic hydrocarbons and suggest that the hitherto unrecognized nitroreductase activity of AKR1C enzymes should be further investigated.


Assuntos
Poluentes Atmosféricos/metabolismo , Membro C3 da Família 1 de alfa-Ceto Redutase/metabolismo , Benzo(a)Antracenos/metabolismo , Células A549 , Ativação Metabólica , Poluentes Atmosféricos/análise , Membro C3 da Família 1 de alfa-Ceto Redutase/antagonistas & inibidores , Membro C3 da Família 1 de alfa-Ceto Redutase/genética , Benzo(a)Antracenos/análise , Biocatálise , Linhagem Celular , Cromatografia Líquida de Alta Pressão , Humanos , Espectrometria de Massas , NAD(P)H Desidrogenase (Quinona)/antagonistas & inibidores , NAD(P)H Desidrogenase (Quinona)/genética , NAD(P)H Desidrogenase (Quinona)/metabolismo , Isoformas de Proteínas/antagonistas & inibidores , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo
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