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1.
Nat Commun ; 12(1): 1042, 2021 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-33589625

RESUMO

Necrotizing enterocolitis (NEC) is a disease of premature infants characterized by acute intestinal necrosis. Current dogma suggests that NEC develops in response to post-natal dietary and bacterial factors, and so a potential role for in utero factors in NEC remains unexplored. We now show that during pregnancy, administration of a diet rich in the aryl hydrocarbon receptor (AHR) ligand indole-3-carbinole (I3C), or of breast milk, activates AHR and prevents NEC in newborn mice by reducing Toll-like receptor 4 (TLR4) signaling in the newborn gut. Protection from NEC requires activation of AHR in the intestinal epithelium which is reduced in mouse and human NEC, and is independent of leukocyte activation. Finally, we identify an AHR ligand ("A18") that limits TLR4 signaling in mouse and human intestine, and prevents NEC in mice when administered during pregnancy. In summary, AHR signaling is critical in NEC development, and maternally-delivered, AHR-based therapies may alleviate NEC.


Assuntos
Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Enterocolite Necrosante/genética , Indóis/administração & dosagem , Leite Humano/fisiologia , Receptores de Hidrocarboneto Arílico/genética , Receptor 4 Toll-Like/genética , Animais , Animais Recém-Nascidos , Fatores de Transcrição Hélice-Alça-Hélice Básicos/agonistas , Fatores de Transcrição Hélice-Alça-Hélice Básicos/imunologia , Citocromo P-450 CYP1A1/genética , Citocromo P-450 CYP1A1/imunologia , Dieta/métodos , Modelos Animais de Doenças , Enterocolite Necrosante/imunologia , Enterocolite Necrosante/patologia , Enterocolite Necrosante/prevenção & controle , Feminino , Regulação da Expressão Gênica , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/imunologia , Mucosa Intestinal/patologia , Ligantes , Exposição Materna , Camundongos , Gravidez , Receptores de Hidrocarboneto Arílico/agonistas , Receptores de Hidrocarboneto Arílico/imunologia , Transdução de Sinais , Suínos , Receptor 4 Toll-Like/imunologia
2.
Ecotoxicol Environ Saf ; 207: 111296, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-32949931

RESUMO

The present study investigated the alleviating role of camel milk (CM) in the mitigation of fenpropathrin (FNP) type II pyrethroid induced oxidative stress, alterations of hepatic (CYP1A1) mRNA expression pattern, and DNA damage using the alkaline comet assay (SCGE) in male rats. Sixty male Sprague-Dawley rats were separated into six groups (n = 10): 1st control (C), 2nd corn oil (CO), 3rd (CM): gavaged CM 2ml/rat, 4th (FNP): gavaged FNP 7.09 mg/kg body weight (BW), 5th (FNP pro/co-treated): gavaged CM firstly for 15 days, then CM + FNP by the same mentioned doses and route, 6th (FNP + CM co-treated): gavaged FNP firstly followed by CM by the same mentioned doses and route. Rats were orally gavaged three times per week, day after day for 60 days. FNP exposure significantly reduced serum glutathione (GSH) levels, but significantly increased serum levels of superoxide dismutase (SOD), catalase (CAT), malondialdehyde (MDA), protein carbonyl (PCO), and 8hydroxy2deoxyguanosine (8OH2dG). Additionally, FNP exposure significantly up-regulated the mRNA expression levels of hepatic CYP1A1 and increased the SCGE indices in whole blood, liver, and spleen tissues of exposed male rats. Administration of CM significantly regulated the FNP induced oxidative stress, reduced hepatic CYP1A1 mRNA expression levels and values of comet assay indices particularly in the (CM + FNP pro/co-treated) group compared to the (FNP + CM co-treated) group. In conclusion, our results indicate, for the first time, that FNP retains an in vivo genotoxic potential at a dose of (1/10 LD50) and up-regulated hepatic CYP1A1 mRNA expression in male rats. Additionally, CM supplements may improve the genotoxic outcomes, oxidative stress, and altered CYP1A1 mRNA expression induced by FNP particularly in the pro/concurrent-treatment compared to the concurrent treatment alone.


Assuntos
Camelus , Citocromo P-450 CYP1A1/genética , Dano ao DNA , Poluentes Ambientais/toxicidade , Leite , Piretrinas/toxicidade , Animais , Catalase/metabolismo , Expressão Gênica/efeitos dos fármacos , Glutationa/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Malondialdeído/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Superóxido Dismutase/metabolismo
3.
Eur J Drug Metab Pharmacokinet ; 45(6): 761-770, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32930952

RESUMO

BACKGROUND AND OBJECTIVE: Deferasirox is an oral iron chelator used to reduce iron levels in iron-overloaded patients with transfusion-dependent anemia or non-transfusion-dependent thalassemia. This study investigated the effects of genetic polymorphisms on the pharmacokinetics of deferasirox in healthy Chinese subjects and constructed a pharmacokinetic prediction model based on physiologic factors and genetic polymorphism data. METHODS: Twenty-eight subjects were enrolled in a randomized, open-label, two-period crossover study, and they received a single dose of one of two formulations of deferasirox (20 mg/kg) with a 7-day washout interval between the two periods. The plasma defersirox concentration was determined using a validated liquid chromatography-tandem mass spectrometry method, and pharmacokinetic parameters were calculated using the noncompartmental method. The polymorphisms of uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1), UGT1A3, multidrug resistance protein 2 (MRP2), cytochrome P450 1A1 (CYP1A1), and breast cancer resistance protein 1 (BCRP1) were genotyped using Sanger sequencing. A back-propagation artificial neural network (BP-ANN) model was used to predict the pharmacokinetics. RESULTS: The UGT1A1 rs887829 C > T single-nucleotide polymorphism (SNP) significantly influenced the area under the plasma concentration-time curve and the terminal half-life. Neither the MRP2 rs2273697 G > A SNP nor BCRP1 rs2231142 G > T SNP altered the absorption, disposition, and excretion of the drug. The BP-ANN model had a high goodness-of-fit index and good coherence between the predicted and measured concentrations (R2 = 0.921). CONCLUSION: Metabolic enzyme-related genetic polymorphisms were more strongly associated with the pharmacokinetics of deferasirox than membrane transporter-related genetic polymorphisms in the Chinese population. TRIAL REGISTRATION: www.Chinadrugtrials.org.cn CTR20191164.


Assuntos
Deferasirox/farmacocinética , Quelantes de Ferro/farmacocinética , Redes Neurais de Computação , Adolescente , Adulto , Área Sob a Curva , Grupo com Ancestrais do Continente Asiático , Estudos Cross-Over , Citocromo P-450 CYP1A1/genética , Composição de Medicamentos , Feminino , Glucuronosiltransferase/genética , Meia-Vida , Voluntários Saudáveis , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas Associadas à Resistência a Múltiplos Medicamentos/genética , Polimorfismo Genético/genética , Polimorfismo de Nucleotídeo Único , Valor Preditivo dos Testes , Adulto Jovem
4.
Ecotoxicol Environ Saf ; 205: 111157, 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-32829211

RESUMO

The fungicide carbendazim (CBM) has been applied all around the world but its potential adverse effects other than its recognized activity as endocrine disruptor in non target organisms have been scarcely studied. The aims of this work were (1) to use a battery of biomarkers that can reflect potential negative effects such as oxidative stress, genotoxicity, neurotoxicity or altered immune response; and (2) to examine biomarkers of detoxification by analyzing the gene expression of cytochrome P4501A1 (CYP1A1) and the multi-xenobiotic resistance protein P-glycoprotein (P-gp) in the freshwater fish Jenynsia multidentata exposed to environmentally relevant concentrations of CBM during 24 h. Fish exposed to 5 µg/L showed inhibition of GST activity and an increase of TBARs contents in gills, the organ of direct contact with waterborne contaminants. Genotoxicity - measured in peripheral blood-was evidenced by the increases of micronuclei frequency when fish were exposed to 5, 10 and 100 µg/L CBM and of nuclear abnormalities (NA) frequency at 0.05, 0.5, 5, 10 and 100 µg/L CBM. The expression inhibition of interleukin (IL-1ß) and tumor necrosis factor a (TNF-α) at 10, and 5 and 10 µg/L CBM, respectively, indicated an altered immune response. The expression of CYP1A1 was down regulated in liver at 10 µg/L and of P-gp at 5 µg/L CBM, indicating a possible slow on CBM metabolization. On the other hand, in gills CYP1A1 decreased at 5 and 10 µg/L while P-gp was induced at 5 and 100 µg/L CBM. Overall, most of these significant effects were detected below 10 µg/L CBM, in a range of realistic concentrations in aquatic ecosystems worldwide.


Assuntos
Benzimidazóis/toxicidade , Carbamatos/toxicidade , Ciprinodontiformes/metabolismo , Citocinas/metabolismo , Micronúcleos com Defeito Cromossômico/induzido quimicamente , Estresse Oxidativo/efeitos dos fármacos , Poluentes Químicos da Água/toxicidade , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Animais , Antioxidantes/metabolismo , Biomarcadores/metabolismo , Ciprinodontiformes/genética , Ciprinodontiformes/imunologia , Citocromo P-450 CYP1A1/genética , Ecossistema , Água Doce/química , Brânquias/efeitos dos fármacos , Brânquias/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Estresse Oxidativo/genética , Estresse Oxidativo/imunologia
5.
Environ Sci Pollut Res Int ; 27(34): 42600-42610, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32712936

RESUMO

Antioxidant enzymes such as glutathione S-transferases (GSTs) and cytochromes P450 (CYPs) are involved in the metabolism and detoxification of cytotoxic compounds, as well as the elimination of reactive oxygen species (ROS). Therefore, alterations in the structure of these enzymes could result in prolonged production of ROS with subsequent risk of development of disorders such as presbycusis. This study aimed to investigate the association between CYP1A1 (rs4646903, rs1048943) and GSTs (GSTM1-deletion, GSTT1-deletion, GSTP1-rs1695) with presbycusis risk in an Iranian population which was followed by an in silico approach. In a case-control study, 280 subjects including 140 cases with presbycusis and 140 healthy controls were enrolled. Genotypes of single-nucleotide polymorphisms (SNPs) were detected by PCR-RFLP method and the genotype of the above mentioned deletions was determined by touchdown PCR. Some bioinformatics tools were employed to evaluate the impact of SNPs on the gene function. SNP analysis revealed that there are significant associations between rs1048943 (AG vs. AA: OR = 2.46, 95%CI = 1.30-4.65, p = 0.006; GG + AG vs. AA: OR = 2.53, 95%CI = 1.36-4.69, p = 0.003; G vs. A: OR = 2.36, 95%CI = 1.33-4.17, p = 0.003) and rs4646903 (C vs. T: OR = 1.45, 95%CI = 1.02-2.06, p = 0.040) variations and increased risk of presbycusis. However, there was no significant association between rs1695 and presbycusis risk. Also, significant associations were observed between GSTM1 (OR = 4.28, 95%CI = 1.18-15.52, p = 0.027) and GSTT1 (OR = 1.64, 95%CI = 1.02-2.65, p = 0.041) deletions and elevated risk of presbycusis. Moreover, the combination analysis revealed a significant association between GSTM1+/GSTT1- genotype and presbycusis susceptibility (OR = 1.63, 95%CI = 1.00-2.67, p = 0.049). In silico analysis revealed that the rs1048943 SNP could influence significantly on the RNA structure of CYP1A1 (distance: 0.1454; p value: 0.1799). Based on our findings, the rs4646903, rs1048943 SNPs as well as GSTM1 and GSTT1 deletions could be considered as genetic risk factors for the development and progression of presbycusis.


Assuntos
Citocromo P-450 CYP1A1 , Presbiacusia , Estudos de Casos e Controles , Biologia Computacional , Citocromo P-450 CYP1A1/genética , Predisposição Genética para Doença , Genótipo , Glutationa Transferase/genética , Humanos , Irã (Geográfico) , Presbiacusia/genética , Fatores de Risco
6.
Life Sci ; 258: 118140, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32730838

RESUMO

AIMS: This study was performed to investigate the expression profile of cytochrome P450 (CYP) isoforms and effects of polycyclic aromatic hydrocarbons (PAHs) and antiepileptic drugs on CYP1 expression in human astrocytoma MOG-G-CCM cells. MAIN METHODS: CYP1A1 and CYP1B1 expression were determined by quantitative real-time polymerase chain reaction, Western blotting, and immunocytochemistry. KEY FINDINGS: MOG-G-CCM cells expressed various CYP isoforms. Among the CYP isoforms analyzed, CYP1B1 showed the highest expression level, followed by CYP1A1. Furthermore, CYP1B1 was localized in both the endoplasmic reticulum and mitochondria. 3-Methylcholanthrene (3-MC), benz[a]anthracene (B[a]A), benzo[a]pyrene (B[a]P), and valproic acid (VPA) increased the expression of CYP1B1 and CYP1A1. The potent aryl hydrocarbon receptor antagonist GNF351 significantly suppressed the 3-MC- and VPA-mediated upregulation of CYP1B1 and CYP1A1. In addition, VPA potentiated the induction of CYP1B1 and CYP1A1 by 3-MC, B[a]A, and B[a]P, although the augmentation of CYP1A1 was more remarkable than that of CYP1B1. In contrast, other antiepileptic drugs (carbamazepine, lamotrigine, levetiracetam, phenytoin) did not affect the 3-MC-mediated upregulation of CYP1B1 and CYP1A1. VPA is known to act as a histone deacetylase (HDAC) inhibitor. Therefore, the effects of trichostatin A, a representative HDAC inhibitor, on CYP1 induction by 3-MC were examined. Trichostatin A enhanced the 3-MC-mediated upregulation of CYP1A1 but not CYP1B1. SIGNIFICANCE: These results partially indicated that VPA may augment the PAH-mediated induction of CYP1B1 and CYP1A1 through the activation of transcription by HDAC inhibition.


Assuntos
Anticonvulsivantes/farmacologia , Citocromo P-450 CYP1A1/genética , Citocromo P-450 CYP1B1/genética , Hidrocarbonetos Policíclicos Aromáticos/farmacologia , Regulação para Cima/efeitos dos fármacos , Ácido Valproico/farmacologia , Astrócitos/efeitos dos fármacos , Astrócitos/metabolismo , Linhagem Celular Tumoral , Humanos , Transcriptoma/efeitos dos fármacos
7.
Aquat Toxicol ; 226: 105558, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32673888

RESUMO

The aryl hydrocarbon receptor (Ahr) is a ligand-activated transcription factor that mediates the toxicity of dioxins and dioxin-like compounds (DLCs) in vertebrates. Two clades of the Ahr family exist in teleosts (Ahr1 and Ahr2), and it has been demonstrated that Ahr2 is the main protein involved in mediating the toxicity of dioxins and DLCs in most teleost species. Recently, we characterized the Atlantic cod (Gadus morhua) Ahr1a and Ahr2a receptors. To further explore a possible subfunction partitioning of Ahr1a and Ahr2a in Atlantic cod we have mapped the expression and localization of ahr1a and ahr2a in early developmental stages. Atlantic cod embryos were continuously exposed in a passive-dosing exposure system to the Ahr agonist, benzo[a]pyrene (B[a]P), from five days post fertilization (dpf) until three days post hatching (dph). Expression of ahr1a, ahr2a, and the Ahr-target genes, cyp1a and ahrrb, was assessed in embryos (8 dpf and 10 dpf) and larvae (3 dph) with quantitative real-time PCR analyses (qPCR), while in situ hybridization was used to assess the localization of expression of ahr1a, ahr2a and cyp1a. Quantitative measurements showed an increased cyp1a expression in B[a]P-exposed samples at all sampling points, and for ahr2a at 10 dpf, confirming the activation of the Ahr-signalling pathway. Furthermore, B[a]P strongly induced ahr2a and cyp1a expression in the cardiovascular system and skin, respectively, of embryos and larvae. Induced expression of both ahr2a and cyp1a was also revealed in the liver of B[a]P-exposed larvae. Our results suggest that Ahr2a is the major subtype involved in mediating responses to B[a]P in early developmental stages of Atlantic cod, which involves transcriptional regulation of biotransformation genes, such as cyp1a. The focused expression of ahr1a in the eye of embryos and larvae, and the presence of ahr2a transcripts in the jaws and fin nodes, further indicate evolved specialized roles of the two Ahrs in ontogenesis.


Assuntos
Citocromo P-450 CYP1A1/metabolismo , Gadus morhua/crescimento & desenvolvimento , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Receptores de Hidrocarboneto Arílico/metabolismo , Animais , Benzo(a)pireno/toxicidade , Citocromo P-450 CYP1A1/genética , Embrião não Mamífero/efeitos dos fármacos , Embrião não Mamífero/metabolismo , Olho/efeitos dos fármacos , Olho/embriologia , Olho/metabolismo , Gadus morhua/genética , Gadus morhua/metabolismo , Larva/efeitos dos fármacos , Larva/genética , Fígado/efeitos dos fármacos , Fígado/crescimento & desenvolvimento , Fígado/metabolismo , Receptores de Hidrocarboneto Arílico/genética , Poluentes Químicos da Água/toxicidade
8.
Aquat Toxicol ; 226: 105566, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32682194

RESUMO

Cytochrome P450 (CYP) enzymes play important roles in the detoxification and bioactivation of environmental contaminants and are involved in the responses to pollution in fish. In this study, we cloned four new CYP1 genes, CYP1A, CYP1B, CYP1C1, and CYP1C2, from black rockfish (Sebastes schlegelii), a dominant and economically important fish species in Korea. This species is at a significant risk of exposure to petrohydrocarbons, such as benzo[a]pyrene(B[a]P), due to frequent oil spills along the Korean coast. Quantitative PCR analysis of CYP1 gene transcription in 12 organs of the fish revealed tissue-specific expression patterns. CYP1A was significantly expressed in the liver, heart, kidneys, and muscle, and CYP1B was significantly expressed in the gills, muscle, and heart. CYP1C1 and CYP1C2 showed similar tissue expression patterns, with the highest levels in the muscle. Furthermore, exposure to an aryl hydrocarbon receptor (AHR) agonist, B[a]P, at 2, 20, and 200 mg/kg body weight showed significant dysregulation of the CYP1A, CYP1B, CYP1C1, and CYP1C2 expression levels in the gills, liver, kidneys, and spleen. The mRNA expression levels of CYP1A and CYP1B were upregulated by 450- and 17-fold, respectively, in the spleen. Compared with their levels in the control, CYP1C1 increased by 45-fold, while CYP1C2 remained unchanged in the gills, indicating differential effects of the polycyclic aromatic hydrocarbon on CYP1 expression in different fish organs. The results suggested that expression profiles of inducible CYP1 enzymes in S. schlegelii might be used as indicators for assessing aquatic contamination by AHR agonists. Determination of the basal and induced expression levels, as well as substrate specificity, of the four CYP1 enzymes may contribute to a better understanding of their roles in the metabolization of toxicants or drugs.


Assuntos
Benzo(a)pireno/toxicidade , Citocromo P-450 CYP1A1/metabolismo , Expressão Gênica/efeitos dos fármacos , Perciformes/metabolismo , Poluentes Químicos da Água/toxicidade , Animais , Citocromo P-450 CYP1A1/genética , Brânquias/efeitos dos fármacos , Brânquias/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Perciformes/genética , Perciformes/crescimento & desenvolvimento , Receptores de Hidrocarboneto Arílico/metabolismo , República da Coreia
9.
Ecotoxicol Environ Saf ; 201: 110808, 2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32516676

RESUMO

Cyprodinil is a broad-spectrum pyrimidine amine fungicide that has been reportedly used worldwide. However, toxicity studies of cyprodinil on aquatic organisms, specifically zebrafish (Danio rerio), are lacking. In our present study, we predicted cyprodinil binding to the aryl hydrocarbon receptor (AhR) by using molecular docking simulation. Then, we used recombinant HepG2 cells and Tg(cyp1a1-12DRE:egfp) transgenic zebrafish to further assess the AhR agonistic activity of cyprodinil. Besides, the significant upregulation of cyp1a1 further verified that statement. Moreover, we found that zebrafish exposure to cyprodinil induced developmental toxicity in the larvae, particularly during cardiac development. The expression levels of cardiac development-related genes, namely tbx5, nkx2.5, gata4, and tnnt2, were markedly altered, which might cause the adverse effects of cyprodinil on cardiac function and development. In summary, we found that cyprodinil, as an AhR agonist, induced development toxicity in zebrafish larvae, especially on cardiac. Data here can assess the potential effects on organisms in the aquatic environment and promote the regulation and safe use of cyprodinil.


Assuntos
Animais Geneticamente Modificados/metabolismo , Larva/efeitos dos fármacos , Pirimidinas/toxicidade , Receptores de Hidrocarboneto Arílico/agonistas , Poluentes Químicos da Água/toxicidade , Peixe-Zebra/metabolismo , Animais , Citocromo P-450 CYP1A1/genética , Citocromo P-450 CYP1A1/metabolismo , Embrião não Mamífero/efeitos dos fármacos , Embrião não Mamífero/metabolismo , Fungicidas Industriais/metabolismo , Coração/efeitos dos fármacos , Coração/embriologia , Células Hep G2 , Humanos , Larva/genética , Larva/metabolismo , Simulação de Acoplamento Molecular , Organogênese/efeitos dos fármacos , Organogênese/genética , Ligação Proteica , Peixe-Zebra/genética
10.
J Food Sci ; 85(6): 1956-1962, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32406939

RESUMO

We evaluated the influence of pine bark extract (PBE) on organs, the cytochrome-P450 (CYP) activities in liver and estrogenic effects in normal and ovariectomized (OVX) female mice. The PBE did not affect organ weights and liver-function indexes (activities of alkaline phosphatase, aspartate amino transferase, and alanine amino transferase) at doses; 0.04%, 0.4%, and 2.0% PBE in the diet, in normal and OVX female mice. In the OVX mice, CYP1A1 activity was significantly higher in the 0.4% and 2.0% PBE groups than in the OVX control group, and in the 0.4% and 2.0% PBE groups were significantly higher than in the 0.04% PBE group. CYP1A2 and 3A4 activities were significantly higher in the 2.0% PBE group than in all other groups. The PBE did not affect uterine weight and femoral bone mineral density at all PBE doses. These results showed that the dose of PBE at the recommended human intake, had no toxic and estrogenic effects in normal female and OVX mice, however, it may need attention to use the excess intake of PBE with some drugs in postmenopausal women.


Assuntos
Osteoporose Pós-Menopausa/tratamento farmacológico , Pinus/química , Casca de Planta/química , Extratos Vegetais/administração & dosagem , Animais , Densidade Óssea/efeitos dos fármacos , Citocromo P-450 CYP1A1/genética , Citocromo P-450 CYP1A1/metabolismo , Citocromo P-450 CYP1A2/genética , Citocromo P-450 CYP1A2/metabolismo , Feminino , Fêmur/química , Fêmur/crescimento & desenvolvimento , Humanos , Camundongos , Tamanho do Órgão/efeitos dos fármacos , Osteoporose Pós-Menopausa/genética , Osteoporose Pós-Menopausa/metabolismo , Osteoporose Pós-Menopausa/fisiopatologia , Ovariectomia , Ovário/metabolismo , Ovário/cirurgia , Extratos Vegetais/efeitos adversos
11.
Toxicology ; 440: 152473, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32360973

RESUMO

Polycyclic aromatic hydrocarbons (PAHs) are environmental toxicants primarily produced during incomplete combustion; some are carcinogens. PAHs can be safely metabolized or, paradoxically, bioactivated via specific cytochrome P450 (CYP) enzymes to more reactive metabolites, some of which can damage DNA and proteins. Among the CYP isoforms implicated in PAH metabolism, CYP1A enzymes have been reported to both sensitize and protect from PAH toxicity. To clarify the role of CYP1A in PAH toxicity, we generated transgenic Caenorhabditis elegans that express CYP1A at a basal (but not inducible) level. Because this species does not normally express any CYP1 family enzyme, this approach permitted a test of the role of basally expressed CYP1A in PAH toxicity. We exposed C. elegans at different life stages to either the PAH benzo[a]pyrene (BaP) alone, or a real-world mixture dominated by PAHs extracted from the sediment of a highly contaminated site on the Elizabeth River (VA, USA). This site, the former Atlantic Wood Industries, was declared a Superfund site due to coal tar creosote contamination that caused very high levels (in the [mg/mL] range) of high molecular weight PAHs within the sediments. We demonstrate that CYP1A protects against BaP-induced growth delay, reproductive toxicity, and reduction of steady state ATP levels. Lack of sensitivity of a DNA repair (Nucleotide Excision Repair)-deficient strain suggested that CYP1A did not produce significant levels of DNA-reactive metabolites from BaP. The protective effects of CYP1A in Elizabeth River sediment extract (ERSE)-exposed nematodes were less pronounced than those seen in BaP-exposed nematodes; CYP1A expression protected against ERSE-induced reduction of steady-state ATP levels, but not other outcomes of exposure to sediment extracts. Overall, we find that in C. elegans, a basal level of CYP1A activity is protective against the examined PAH exposures.


Assuntos
Benzo(a)pireno/antagonistas & inibidores , Benzo(a)pireno/toxicidade , Caenorhabditis elegans/metabolismo , Citocromo P-450 CYP1A1/genética , Hidrocarbonetos Policíclicos Aromáticos/antagonistas & inibidores , Hidrocarbonetos Policíclicos Aromáticos/toxicidade , Poluentes Químicos da Água/toxicidade , Peixe-Zebra/metabolismo , Trifosfato de Adenosina/metabolismo , Animais , Animais Geneticamente Modificados , Citocromo P-450 CYP1A1/metabolismo , Reparo do DNA/efeitos dos fármacos , Embrião não Mamífero , Larva/efeitos dos fármacos , Larva/crescimento & desenvolvimento , Peso Molecular , Reprodução/efeitos dos fármacos
12.
Toxicology ; 438: 152458, 2020 05 30.
Artigo em Inglês | MEDLINE | ID: mdl-32289347

RESUMO

Kynurenine (Kyn) plays an important role as an immune check-point molecule and regulates various immune responses through its aryl hydrocarbon receptor (Ahr). Kyn is synthesized by indoleamine 2,3-dioxygenase (Ido) and tryptophan 2,3-dioxygenase (Tdo). Ido contributes approximately 90% of tryptophan catabolism. Although Kyn is increased in various liver disorders, the roles of Kyn in liver injury are complicated because Ido1, Ido2, and Tdo are activated in different cell types. In this study, the roles of Ido2 in carbon tetrachloride (CCl4; 1 ml/kg, i.p.)-induced acute liver injury were examined using Ido2 knockout mice and Ido2 inhibitor. After CCl4 treatment, the ratio of Kyn to tryptophan and levels of Kyn in the liver were increased, accompanied by activation of Ahr-mediated signaling, as revealed by increased nuclear Ahr and Cyp1a1 mRNA. Knockout of Ido2 (Ido2-/-) and treatment with Ido2 inhibitor 1-methyl-D-tryptophan (D-1MT; 100 mg/kg, i.p.) attenuated CCl4-induced liver injury, with decreased induction of Ahr-mediated signaling. Administration of D-Kyn (100 mg/kg, i.p.) to Ido2-/- mice canceled the effect of Ido2 deficiency and exacerbated acute liver damage by CCl4 treatment. In addition, liver fibrosis induced by repeated CCl4 administration was suppressed in Ido2-/- mice. In conclusion, the action of Ido2 and Kyn in the liver may prevent severe hepatocellular damage and liver fibrosis.


Assuntos
Tetracloreto de Carbono , Doença Hepática Induzida por Substâncias e Drogas/enzimologia , Indolamina-Pirrol 2,3,-Dioxigenase/metabolismo , Cinurenina/metabolismo , Cirrose Hepática Experimental/enzimologia , Fígado/enzimologia , Animais , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/genética , Doença Hepática Induzida por Substâncias e Drogas/patologia , Citocromo P-450 CYP1A1/genética , Citocromo P-450 CYP1A1/metabolismo , Progressão da Doença , Inibidores Enzimáticos/farmacologia , Hepatócitos/efeitos dos fármacos , Hepatócitos/enzimologia , Hepatócitos/patologia , Indolamina-Pirrol 2,3,-Dioxigenase/antagonistas & inibidores , Indolamina-Pirrol 2,3,-Dioxigenase/deficiência , Indolamina-Pirrol 2,3,-Dioxigenase/genética , Fígado/efeitos dos fármacos , Fígado/patologia , Cirrose Hepática Experimental/induzido quimicamente , Cirrose Hepática Experimental/genética , Cirrose Hepática Experimental/patologia , Camundongos Endogâmicos C57BL , Camundongos Knockout , Receptores de Hidrocarboneto Arílico/genética , Receptores de Hidrocarboneto Arílico/metabolismo , Transdução de Sinais
13.
Food Chem ; 319: 126578, 2020 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-32187570

RESUMO

For clementine juice, previous data indicate a possible food-drug interaction with substrates of key enzymes responsible for drug metabolism (i.e. cytochrome P450 [CYP] 3A4, CYP1A2). However, which compounds in clementine juice are responsible for these effects are unknown. Therefore, we aimed to identify the compounds in clementine juice provoking metabolic enzyme inhibition or induction. The results demonstrated that the flavonoid fraction of clementine juice provoked induction of several genes and inhibition of both CYP3A4 and CYP1A2, matching effects observed with whole clementine juice. CYP1A2 inhibition and induction can most likely be attributed to nobiletin, sinensetin, and tangeretin. Tangeretin was the only compound causing CYP3A4 induction while CYP3A4 inhibition was most likely the result of additive or synergistic effects caused by several compounds. Thus, whenever evaluating the clinical relevance of clementine interactions, flavonoid contents should be reported because these might explain differences between cultivars and harvests.


Assuntos
Citrus/química , Flavonas/farmacocinética , Flavonoides/farmacocinética , Interações Alimento-Droga , Subfamília B de Transportador de Cassetes de Ligação de ATP/genética , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Linhagem Celular , Citocromo P-450 CYP1A1/genética , Citocromo P-450 CYP1A2/genética , Citocromo P-450 CYP1A2/metabolismo , Inibidores do Citocromo P-450 CYP1A2/farmacologia , Citocromo P-450 CYP3A/genética , Citocromo P-450 CYP3A/metabolismo , Inibidores do Citocromo P-450 CYP3A/farmacologia , Flavonoides/análise , Frutas/química , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Receptor 1 de Sinal de Orientação para Peroxissomos/genética , Receptor 1 de Sinal de Orientação para Peroxissomos/metabolismo , Receptores de Hidrocarboneto Arílico/genética , Receptores de Hidrocarboneto Arílico/metabolismo
14.
Cell Physiol Biochem ; 54(1): 126-141, 2020 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-32017483

RESUMO

BACKGROUND/AIMS: Serotonin (5-hydroxytryptamine, 5-HT) is a neurotransmitter and hormone with important physiological functions in many organs, including the intestine. We have previously shown that 5-HT activates the aryl hydrocarbon receptor (AhR) in intestinal epithelial cells (IECs) via a serotonin transporter (SERT)-dependent mechanism. AhR is a nuclear receptor that binds a variety of molecules including tryptophan (TRP) metabolites to regulate physiological processes in the intestine including xenobiotic detoxification and immune modulation. We hypothesized that 5-HT activates AhR indirectly by interfering with metabolic clearance of AhR ligands by cytochrome P450 1A1 (CYP1A1). METHODS: Inhibition of CYP1A1 activity by 5-HT was assessed in the human intestinal epithelial cell line Caco-2 and recombinant CYP1A1 microsomes using both luciferase and LC-MS/MS. Degradation of 5-HT by recombinant CYP1A1 was measured by LC-MS/MS. For in vitro studies, CYP1A1 and CYP1B1 mRNA expression levels were measured by RT-PCR and CYP1A1 activity was measured by ethoxyresorufin-O-deethylase (EROD) assays. For in vivo studies, AhR ligands were administered to SERT KO mice and WT littermates and intestinal mucosa CYP1A1 mRNA was measured. RESULTS: We show that 5-HT inhibits metabolism of both the pro-luciferin CYP1A1 substrate Luc-CEE as well as the high affinity AhR ligand 6-formylindolo[3,2-b] carbazole (FICZ). Recombinant CYP1A1 assays revealed that 5-HT is metabolized by CYP1A1 in an NADPH dependent manner. Treatment with 5-HT in TRP-free medium, which is devoid of trace AhR ligands, showed that 5-HT requires the presence of AhR ligands to activate AhR. Cotreatment with 5-HT and FICZ confirmed that 5-HT potentiates induction of AhR target genes by AhR ligands. However, this was only true for ligands which are CYP1A1 substrates such as FICZ. Administration of ß-napthoflavone by gavage or indole-3-carbinol via diet to SERT KO mice revealed that lack of SERT impairs intestinal AhR activation. CONCLUSION: Our studies provide novel evidence of crosstalk between serotonergic and AhR signaling where 5-HT can influence the ability of AhR ligands to activate the receptor in the intestine.


Assuntos
Citocromo P-450 CYP1A1/metabolismo , Receptores de Hidrocarboneto Arílico/metabolismo , Serotonina/farmacologia , Transcrição Genética/efeitos dos fármacos , Animais , Células CACO-2 , Carbazóis/farmacologia , Citocromo P-450 CYP1A1/genética , Citocromo P-450 CYP1B1/genética , Citocromo P-450 CYP1B1/metabolismo , Humanos , Ligantes , Masculino , Camundongos , Camundongos Knockout , RNA Mensageiro/metabolismo , Receptores de Hidrocarboneto Arílico/química , Proteínas Recombinantes/biossíntese , Proteínas Recombinantes/genética , Proteínas da Membrana Plasmática de Transporte de Serotonina/deficiência , Proteínas da Membrana Plasmática de Transporte de Serotonina/genética , Transdução de Sinais/efeitos dos fármacos , Especificidade por Substrato , beta-Naftoflavona/administração & dosagem
15.
Cell Immunol ; 349: 104047, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32019673

RESUMO

The polarization of macrophages is critical to inflammation and tissue repair, with unbalanced macrophage polarization associated with critical dysfunctions of the immune system. Cytochrome P450 1A1 (CYP1A1) is a hydroxylase mainly controlled by the inflammation-limiting aryl hydrocarbon receptor (AhR), which plays a critical role in mycoplasma infection, oxidative stress injury, and cancer. Arginase-1 (Arg-1) is a surrogate for polarized alternative macrophages and is important to the production of nitric oxide (NO) by the modulation of arginine. In the present study, we found CYP1A1 to be upregulated in IL-4-stimulated mouse peritoneal macrophages (PMs) and human peripheral blood monocytes. Using CYP1A1-overexpressing RAW264.7 cells (CYP1A1/RAW) we found that CYP1A1 augmented Arg-1 expression by strengthening the activation of the JAK1/STAT6 signaling pathway in macrophages treated with IL-4. 15(S)-HETE, a metabolite of CYP1A1 hydroxylase, was elevated in IL-4-induced CYP1A1/RAW cells. Further, in macrophages, the loss-of-CYP1A1-hydroxylase activity was associated with reduced IL-4-induced Arg-1 expression due to impaired 15(S)-HETE generation. Of importance, CYP1A1 overexpressing macrophages reduced the inflammation associated with LPS-induced peritonitis. Taken together, these findings identified a novel signaling axis, CYP1A1-15(S)-HETE-JAK1-STAT6, that may be a promising target for the proper maintenance of macrophage polarization and may also be a means by which to treat immune-related disease due to macrophage dysfunction.


Assuntos
Arginase/biossíntese , Citocromo P-450 CYP1A1/fisiologia , Janus Quinase 1/antagonistas & inibidores , Macrófagos Peritoneais/efeitos dos fármacos , Peritonite/prevenção & controle , Fator de Transcrição STAT6/antagonistas & inibidores , Transdução de Sinais/efeitos dos fármacos , Ácido 12-Hidroxi-5,8,10,14-Eicosatetraenoico/farmacologia , Transferência Adotiva , Animais , Araquidonato 15-Lipoxigenase/fisiologia , Arginase/genética , Citocromo P-450 CYP1A1/biossíntese , Citocromo P-450 CYP1A1/genética , Endotoxinas/toxicidade , Humanos , Ácidos Hidroxieicosatetraenoicos/biossíntese , Ácidos Hidroxieicosatetraenoicos/genética , Ácidos Hidroxieicosatetraenoicos/farmacologia , Interleucina-4/farmacologia , Leucócitos Mononucleares/efeitos dos fármacos , Leucócitos Mononucleares/metabolismo , Leucócitos Mononucleares/transplante , Macrófagos Peritoneais/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Peritonite/induzido quimicamente , Células RAW 264.7 , Interferência de RNA , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , Receptores Citoplasmáticos e Nucleares/biossíntese , Receptores Citoplasmáticos e Nucleares/genética , Células THP-1 , Regulação para Cima/efeitos dos fármacos
16.
Asian Pac J Cancer Prev ; 21(1): 243-248, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31983191

RESUMO

BACKGROUND: CYP1A1 is an enzyme in phase I of the cytochrome P450 (CYP) superfamily, and plays a key role in detoxification of carcinogens. Host genetic predisposition in the CYP1A1 may be associated with an increased susceptibility to cervical cancer.The study aimed to evaluate four common polymorphisms of the CYP1A1 and cervical cancer susceptibility among Northeast Thai women. METHODS: A case-control study was conducted involving 204 patients with squamous cell cervical cancer (SCCA) and 204 age-matched healthy controls. DNA was extracted from peripheral blood leucocytes. CYP1A1 m1, m3, and m4 genotypes were detected using PCR-RFLP, whereas the CYP1A1 m2 genotype was investigated using real-time PCR. Haplotype analysis was performed using PHASE algorithm version 2.1.1. RESULTS: CYP1A1 m3 was monomorphic. Association between the common CYP1A1 polymorphisms, m1 and m2, and cervical cancer risk was not observed (p>0.05), nor was any association found between the m1-m2-m4 haplotype and cervical cancer risk (p>0.05). Interestingly, the CA genotype of CYP1A1 m4 was observed in 30.88% of the cervical cancer patients but was absent in healthy controls. CONCLUSION: Our results demonstrated a possible involvement of the CYP1A1 m4 polymorphism but no other common polymorphisms (viz., m1, m2, and m3) in the risk for cervical cancer.This finding may be useful when screening for risk of cervical cancer among Northeast Thai women.
.


Assuntos
Biomarcadores Tumorais/genética , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patologia , Citocromo P-450 CYP1A1/genética , Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Feminino , Seguimentos , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Fatores de Risco
17.
J Biochem Mol Toxicol ; 34(1): e22414, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31626383

RESUMO

Epigenetic alterations are essential for normal mammalian development and regulation of gene expression. In this study, we aimed to determine if an enigmatic endogenous ligand of the aryl hydrocarbon receptor (AHR), 6-formylindolo[3,2-b]carbazole (FICZ), and methionine (Meth) have an epigenetic impact on AHR-regulated cytochrome P450 1A1 and B1 (CYP1A1 and CYP1B1) gene expression. Human hepatoma (HepG2-XRE-Luc and huh7) cells were exposed to FICZ in a medium with and without Meth supplementation. Selective and transient silencing of CYP1A1 but not CYP1B1 were seen by FICZ. Here we found that FICZ transiently represses CYP1A1 by targeting DNA (cytosine-5)-methyltransferase 3A (DNMT3A) and concomitant DNA methylation of the CYP1A1 promoter gene. Treatments with 5-aza-dC augmented CYP1A1 transcription activity. Our results reveal a new mechanism for transient activation of AHR by FICZ that can negatively and positively influence gene expression, and highlight the regulatory role of Meth on the CYP1A1 gene expression.


Assuntos
Carbazóis/farmacologia , Ilhas de CpG , Citocromo P-450 CYP1A1/genética , Citocromo P-450 CYP1B1/genética , Metilação de DNA , Regiões Promotoras Genéticas , Linhagem Celular Tumoral , DNA (Citosina-5-)-Metiltransferases/genética , Humanos , Transcrição Genética
18.
J Steroid Biochem Mol Biol ; 196: 105507, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31669572

RESUMO

Aromatase (CYP19A1) converts androgens into estrogens and is required for female sexual development and growth and development in both sexes. CYP19A1 is a member of cytochrome P450 family of heme-thiolate monooxygenases located in the endoplasmic reticulum and depends on reducing equivalents from the reduced nicotinamide adenine dinucleotide phosphate via the cytochrome P450 oxidoreductase coded by POR. Both the CYP19A1 and POR genes are highly polymorphic, and mutations in both these genes are linked to disorders of steroid biosynthesis. We have previously shown that R264C and R264H mutations in CYP19A1, as well as mutations in POR, reduce CYP19A1 activity. The R264C is a common polymorphic variant of CYP19A1, with high frequency in Asian and African populations. Polymorphic alleles of POR are found in all populations studied so far and, therefore, may influence activities of CYP19A1 allelic variants. So far, the effects of variations in POR on enzymatic activities of allelic variants of CYP19A1 or any other steroid metabolizing cytochrome P450 proteins have not been studied. Here we are reporting the effects of three POR variants on the aromatase activities of two CYP19A1 variants, R264C, and R264H. We used bacterially expressed and purified preparations of WT and variant forms of CYP19A1 and POR and constructed liposomes with embedded CYP19A1 and POR proteins and assayed the CYP19A1 activities using radiolabeled androstenedione as a substrate. With the WT-POR as a redox partner, the R264C-CYP19A1 showed only 15% of aromatase activity, but the R264H had 87% of aromatase activity compared to WT-CYP19A1. With P284L-POR as a redox partner, R264C-CYP19A1 lost all activity but retained 6.7% of activity when P284T-POR was used as a redox partner. The R264H-CYP19A1 showed low activities with both the POR-P284 L as well as the POR-P284 T. When the POR-Y607C was used as a redox partner, the R264C-CYP19A1 retained approximately 5% of CYP19A1 activity. Remarkably, The R264H-CYP19A1 had more than three-fold higher activity compared to WT-CYP19A1 when the POR-Y607C was used as the redox partner, pointing toward a beneficial effect. The slight increase in activity of R264C-CYP19A1 with the P284T-POR and the three-fold increase in activity of the R264H-CYP19A1 with the Y607C-POR point toward a conformational effect and role of protein-protein interaction governed by the R264C and R264H substitutions in the CYP19A1 as well as P284 L, P284 T and Y607C variants of POR. These studies demonstrate that the allelic variants of P450 when present with a variant form of POR may show different activities, and combined effects of variations in the P450 enzymes as well as in the POR should be considered when genetic data are available. Recent trends in the whole-exome and whole-genome sequencing as diagnostic tools will permit combined evaluation of variations in multiple genes that are interdependent and may guide treatment options by adjusting therapeutic interventions based on laboratory analysis.


Assuntos
Hiperplasia Suprarrenal Congênita/genética , Aromatase/genética , Aromatase/metabolismo , Sistema Enzimático do Citocromo P-450/genética , Sistema Enzimático do Citocromo P-450/metabolismo , Hiperplasia Suprarrenal Congênita/enzimologia , Hiperplasia Suprarrenal Congênita/metabolismo , Substituição de Aminoácidos/genética , Substituição de Aminoácidos/fisiologia , Androstenodiona/metabolismo , Arginina/genética , Aromatase/química , Aromatase/deficiência , Cisteína/genética , Citocromo P-450 CYP1A1/química , Citocromo P-450 CYP1A1/deficiência , Citocromo P-450 CYP1A1/genética , Citocromo P-450 CYP1A1/metabolismo , Ativação Enzimática/genética , Histidina/genética , Humanos , Modelos Moleculares , Mutação de Sentido Incorreto/fisiologia , Polimorfismo de Nucleotídeo Único , Conformação Proteica , Relação Estrutura-Atividade
19.
Toxicon ; 173: 75-93, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31734251

RESUMO

Plant-based materials used in the production of pig feed are very often contaminated with deoxynivalenol and zearalenone. Daily intake of small amounts of these mycotoxins with feed induces various subclinical states in gilts and influences different biological processes. The aim of this preclinical study was to determine the correlation between monotonic doses of zearalenone and deoxynivalenol (40 µg/kg body weight and 12 µg/kg body weight, respectively, administered over a period of 42 days) and the immunohistochemical expression of estrogen receptors in the intestinal tract and the mRNA expression of selected colonic enzymes. The immunohistochemical expression of estrogen receptor alpha was observed in the colon, but its intensity varied in different weeks of exposure. A minor increase in estrogen receptor beta expression was noted only in the colon, whereas the expression of cytochrome P450 1A1 enzyme mRNA and mRNA isoform of the glutathione S-transferase π gene decreased. The observed correlations suggest that the risk of loss of control over the biotransformation and biological activity of the parent compounds in distal intestinal mucosa is delayed.


Assuntos
Estrogênios não Esteroides/toxicidade , Mucosa Intestinal/fisiologia , Venenos/toxicidade , Receptores Estrogênicos/metabolismo , Suínos/fisiologia , Tricotecenos/toxicidade , Zearalenona/toxicidade , Animais , Peso Corporal , Colo , Citocromo P-450 CYP1A1/genética , Citocromo P-450 CYP1A1/metabolismo , Feminino , Glutationa Transferase/genética , Glutationa Transferase/metabolismo , Intestinos , Micotoxinas , RNA Mensageiro/metabolismo , Sus scrofa
20.
Anal Chim Acta ; 1093: 106-114, 2020 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-31735203

RESUMO

Single nucleotide polymorphism (SNP) was associated with many human diseases, therefore, SNP detection was important for early diagnosis and clinical prognosis. Herein, a simple and accurate method for visual detection SNP sites (A/A, G/G, A/G) in CYP1A1 gene related to cancers based on colloidal gold nucleic acid strip biosensor and primer-specific polymerase chain reaction (PCR) was established. This method could directly distinguish SNP sites on strip biosensor by introducing twice PCR amplifications. The second PCR (primer-specific PCR) was performed using specific product of the first PCR as template, thus this twice PCR could reduce non-specific amplification greatly and obtain target product. In addition, single-strand or double-strand DNA (ssDNA or dsDNA) was accurately produced by introducing mismatched base at the 3' end of forward primers in primer-specific PCR. The designed strip biosensor could only combine with the ssDNA, thus visual detection of SNP could be achieved within 10 min by color difference of a pair of strips. 61 human blood samples by this method were identical with those of pyrosequencing. This method had the advantages of rapid, visual and low-cost and was expected to be applied in medical diagnosis.


Assuntos
Técnicas Biossensoriais/métodos , Citocromo P-450 CYP1A1/genética , DNA/sangue , Coloide de Ouro/química , Polimorfismo de Nucleotídeo Único , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/genética , Colorimetria/métodos , DNA/genética , Sondas de DNA/química , Ouro/química , Humanos , Nanopartículas Metálicas/química , Reação em Cadeia da Polimerase/métodos
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