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[PMID]:29391002
[Au] Autor:Kahaliw W; Hellman B; Engidawork E
[Ad] Endereço:Department of Pharmacology, School of Pharmacy, College of Medicine and Health Sciences, University of Gondar, P. O. Box: 196, Gondar, Ethiopia. wubayehu.kahaliw@uog.edu.et.
[Ti] Título:Genotoxicity study of Ethiopian medicinal plant extracts on HepG2 cells.
[So] Source:BMC Complement Altern Med;18(1):45, 2018 Feb 01.
[Is] ISSN:1472-6882
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Most of herbal medicines are used without any standard safety and toxicological trials although common assumption is that these products are nontoxic. However, this assumption is incorrect and dangerous, so toxicological studies should be done for herbal drugs. Although Pterolobium stellatum, Otostegia integrifolia and Vernonia amygdalina root extracts are frequently used in Ethiopian traditional medicine, there are no evidences of their active toxic compounds. Therefore, we made an effort to assess probable genotoxic effect of these plant extracts on DNA of human hematoma (HepG ) cells using alkaline comet assay. METHODS: Genotoxic effects of extracts were evaluated using single cell gel electrophoresis (SCGE) method on HepG cell. Regarding comet data, the average mean tail intensities (TI) from each individual experiment and treatment (usually at least 3 cultures/treatment) were pooled and the average mean TI was used as an indicator of DNA damage and the standard error of mean (SEM) as the measure of variance. RESULTS: DNA damage in the form of comet tail has been observed for 1 and 0.5 mg/ml P. stellatum chloroform and 80% methanol extracts on HepG cells, respectively. The chloroform extract of P. stellatum showed increased tail DNA percentage in a concentration dependent manner. Comet tail length in the chloroform P. stellatum extract treated cells (1 mg/ml) was significantly higher by 89% (p < 0.05) compared to vehicle treated controls. The rest of test extracts seemed to be without genotoxic effect up to a concentration of 0.5 mg/ml. CONCLUSIONS: Our findings show that two extracts from one plant evaluated have a genotoxic potential in vitro which calls for a more thorough safety evaluation. Such evaluation should include other end-points of genotoxicity apart from DNA damage, and possibly also pure compounds.
[Mh] Termos MeSH primário: Dano ao DNA/efeitos dos fármacos
Mutagênicos/toxicidade
Extratos Vegetais/toxicidade
Plantas Medicinais/química
[Mh] Termos MeSH secundário: Sobrevivência Celular/efeitos dos fármacos
Ensaio Cometa
Fabaceae/química
Células Hep G2
Seres Humanos
Lamiaceae/química
Testes de Mutagenicidade
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Mutagens); 0 (Plant Extracts)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180301
[Lr] Data última revisão:
180301
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180203
[St] Status:MEDLINE
[do] DOI:10.1186/s12906-017-2056-x


  2 / 6543 MEDLINE  
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[PMID]:29284781
[Au] Autor:Buchynska LG; Brieieva OV; Iurchenko NP; Protsenko VV; Nespryadko SV
[Ad] Endereço:R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology, NAS of Ukraine, Kyiv 03022, Ukraine.
[Ti] Título:DNA damage in tumor cells and peripheral blood lymphocytes of endometrial cancer patients assessed by the comet assay.
[So] Source:Exp Oncol;39(4):299-303, 2017 Dec.
[Is] ISSN:1812-9269
[Cp] País de publicação:Ukraine
[La] Idioma:eng
[Ab] Resumo:To date, genome instability is considered to be a common feature not only of tumor cells, but also of non-malignant cells of cancer patients, including peripheral blood lymphocytes (PBLs). The issue of the association between genome instability in tumor cells and PBLs, as well as of its relationship with tumor progression remains poorly understood. AIM: To evaluate the level DNA damage in tumor cells and PBLs of endometrial cancer (EC) patients with regard to clinical and morphological characteristics of the patients. MATERIALS AND METHODS: DNA damage was assessed in 106 PBLs samples and 42 samples of tumor cell suspension from EC patients by comet assay. PBLs from 30 healthy women were used as control. The level of DNA damage was expressed as the percentage of DNA in the comet tails (% tail DNA). RESULTS: It was revealed that the amount of DNA damage in PBLs of EC patients was 2.2 times higher in comparison with that of healthy donors (8.3 ± 0.7 and 3.7 ± 0.4% tail DNA, respectively) (p < 0.05). In this study, no association between the levels of DNA damage in endometrial tumor cells and PBLs was observed (r = 0.11; p > 0.05). The amounts of DNA damage both in tumor cells and PBLs were not related to the degree of tumor differentiation as well as the depth of myometrial invasion, but depended on the body mass index (BMI) of EC patients: high level of lesions was observed in patients with elevated BMI values. Furthermore, the level of DNA damage in tumor cells was associated to familial aggregation of cancer and was significantly higher in endometrial cells from patients with family history of cancer vs that from EC patients with sporadic tumors (32.3 ± 2.9 and 22.8 ± 1.8% tail DNA, respectively) (p < 0.05). It was also found that for women who had high level of DNA damage in PBLs, the risk of EC was greater (odds ratio value of 3.5) compared to those with low level of such lesions. CONCLUSION: Genome instability that appears as an increased level of DNA damage in tumor cells and PBLs of EC patients is associated with BMI and family history of cancer and can reflect a predisposition to cancer.
[Mh] Termos MeSH primário: Neoplasias do Endométrio/genética
Neoplasias do Endométrio/patologia
Instabilidade Genômica
Linfócitos/patologia
[Mh] Termos MeSH secundário: Ensaio Cometa
Dano ao DNA
Feminino
Seres Humanos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180223
[Lr] Data última revisão:
180223
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171230
[St] Status:MEDLINE


  3 / 6543 MEDLINE  
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[PMID]:29394011
[Au] Autor:Saladino R; Chiocchini U; Botta G; Delfino M; Conigliaro R; Mosesso P
[Ti] Título:Free radical scavenging capacity and protective effect of natural substances in peloids from the thermal spring pool Bagnaccio (Viterbo, Italy).
[So] Source:J Cosmet Sci;67(2):71-92, 2016 Mar-Apr.
[Is] ISSN:1525-7886
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Natural peloids from sulfurous thermal springs are largely used in cosmetic and pelotherapy for the treatment of different dermatological conditions, including skin aging, dermatitis, and other eczemas. The beneficial effects are correlated to mineralogical and other thermal properties, as well as to the presence of natural substances with specific antioxidant activity. Few data are available for the comparison between natural peloids and synthetic (i.e., artificially maturated) muds. In this context, the natural substances and antioxidant activity of natural white mud (WM) and dark mud (DM) peloids from the sulfurous thermal spring pool Bagnaccio (Viterbo, Italy) have been studied in detail to evaluate possible relationships between physicochemical properties and therapeutic effect. A large panel of natural substances in WM and DM were characterized for the first time by ³¹P-nuclear magnetic resonance and gas chromatography associated to mass spectrometry analysis. Polar fractions of WM and DM peloids were characterized by the presence of several bioactive natural compounds, showing high antioxidant activity and DNA protective effect, as evaluated by 2,2-diphenyl-1-picrylhydrazyl assay, and hydrogen peroxide­induced DNA breakage in the alkaline comet assay. The antioxidant activity and DNA protective effect could be attributed to radical scavenging rather than a modulatory effect on the induced DNA repair, and are of order of intensity higher than that reported for synthetic muds.
[Mh] Termos MeSH primário: Alcaloides/farmacologia
Depuradores de Radicais Livres/farmacologia
Hidrocarbonetos Aromáticos/farmacologia
Fenóis/farmacologia
Terpenos/farmacologia
[Mh] Termos MeSH secundário: Alcaloides/química
Alcaloides/isolamento & purificação
Alcanos/química
Alcanos/isolamento & purificação
Alcanos/farmacologia
Alcenos/química
Alcenos/isolamento & purificação
Alcenos/farmacologia
Animais
Compostos de Bifenilo/antagonistas & inibidores
Compostos de Bifenilo/química
Células CHO
Linhagem Celular Tumoral
Sobrevivência Celular/efeitos dos fármacos
Ensaio Cometa
Cricetulus
DNA/efeitos dos fármacos
Depuradores de Radicais Livres/química
Depuradores de Radicais Livres/isolamento & purificação
Fontes Termais
Seres Humanos
Hidrocarbonetos Aromáticos/química
Hidrocarbonetos Aromáticos/isolamento & purificação
Peróxido de Hidrogênio/antagonistas & inibidores
Peróxido de Hidrogênio/química
Itália
Espectroscopia de Ressonância Magnética
Camundongos
Terapia por Lama
Fenóis/química
Fenóis/isolamento & purificação
Picratos/antagonistas & inibidores
Picratos/química
Terpenos/química
Terpenos/isolamento & purificação
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Alkaloids); 0 (Alkanes); 0 (Alkenes); 0 (Biphenyl Compounds); 0 (Free Radical Scavengers); 0 (Hydrocarbons, Aromatic); 0 (Phenols); 0 (Picrates); 0 (Terpenes); 9007-49-2 (DNA); BBX060AN9V (Hydrogen Peroxide); DFD3H4VGDH (1,1-diphenyl-2-picrylhydrazyl)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180222
[Lr] Data última revisão:
180222
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180203
[St] Status:MEDLINE


  4 / 6543 MEDLINE  
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[PMID]:29251483
[Au] Autor:Ryu AR; Bang IC; Lee SA; Lee MY
[Ti] Título:The protective role of phytochemicals on TiO2 nanoparticles-induced DNA damage in lymphocytes.
[So] Source:J Environ Biol;37(5):913-7, 2016 09.
[Is] ISSN:0254-8704
[Cp] País de publicação:India
[La] Idioma:eng
[Ab] Resumo:The adverse health effect of nanoparticles is of concern for humans and environment. In the present study, TiO2-nanoparticles (TiO2-NPs)-induced oxidative DNA damage in lymphocytes was measured by comet assay. 80 mg ml-1 TiO2-NPs induced approximately 3-fold increase in DNA damage than in the PBS-control group as measured by olive tail moment. However, on treating vitamin C and N-acetylcysteine, DNA damage was effectively protected in a concentration dependent manner. Moreover, the protective effect of several phytochemicals including berberine, resveratrol, sulforaphane, and curcumin on DNA damage caused by TiO2-NPs was manifested. The increased olive tail moment induced by TiO2-NPs was effectively inhibited by treatment with these phytochemicals. Especially, olive tail moment of 5 mg ml-1 berberine-treated group was significantly reduced down to the level of control group, showing almost complete protection. Taken together, the protective effect of phytochemicals against DNA damage by TiO2-NPs may be applied for the development of antidote for TiO2 toxicity.
[Mh] Termos MeSH primário: Dano ao DNA/efeitos dos fármacos
Linfócitos/efeitos dos fármacos
Nanopartículas Metálicas/toxicidade
Compostos Fitoquímicos/farmacologia
Titânio/toxicidade
[Mh] Termos MeSH secundário: Animais
Ensaio Cometa
Masculino
Nanopartículas Metálicas/química
Ratos Sprague-Dawley
Titânio/química
[Pt] Tipo de publicação:RESEARCH SUPPORT, NON-U.S. GOV'T; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Phytochemicals); 15FIX9V2JP (titanium dioxide); D1JT611TNE (Titanium)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180222
[Lr] Data última revisão:
180222
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171219
[St] Status:MEDLINE


  5 / 6543 MEDLINE  
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[PMID]:29248571
[Au] Autor:Jarolim K; Wolters K; Woelflingseder L; Pahlke G; Beisl J; Puntscher H; Braun D; Sulyok M; Warth B; Marko D
[Ad] Endereço:University of Vienna, Faculty of Chemistry, Department of Food Chemistry and Toxicology, Währinger Straße 38, 1090 Vienna, Austria.
[Ti] Título:The secondary Fusarium metabolite aurofusarin induces oxidative stress, cytotoxicity and genotoxicity in human colon cells.
[So] Source:Toxicol Lett;284:170-183, 2018 Mar 01.
[Is] ISSN:1879-3169
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Aurofusarin (AURO), a dimeric naphthoquinone, is produced by Fusarium fungi. Although frequently found in food and feed, toxicological studies are limited. Hence, the in vitro toxicity of AURO was investigated in the colon adenocarcinoma cell line HT29 and the non-tumorigenic colon cells HCEC-1CT. Cytotoxic effects were found at concentrations ≥1 µM by evaluating mitochondrial activity (WST-1) and cellular proliferation (sulforhodamine B assay). 10 µM of AURO induced a decrease of cells in the S-phase, measured by flow cytometry. Confocal microscopy revealed AURO-mediated increase of intracellular p53 protein. In accordance, DNA-damage was seen in the comet assay (≥1 µM) together with enhanced levels of formamidopyrimidine-DNA-glycosylase (fpg)-sensitive sites, indicative for oxidative stress. An increase of intracellular reactive oxygen species was observed in the dichlorofluorescein (DCF) assay (≥5 µM). The GSSG/GSH ratio was elevated, but no impact on redox-sensitive Nrf2-dependent genes (Nrf2, γ-GCL, NQO1) was found at the gene expression level. However, induction of cytochrome P450 monooxygenase (CYP) 1A1 was measured at the gene expression and protein level. In conclusion, these in vitro data suggest that, when co-occurring, AURO might be considered as a potential contributor to the overall toxicity of respective Fusarium mycotoxin mixtures.
[Mh] Termos MeSH primário: Colo/efeitos dos fármacos
Dano ao DNA
Fusarium/metabolismo
Mutagênicos/toxicidade
Naftoquinonas/toxicidade
Estresse Oxidativo/efeitos dos fármacos
[Mh] Termos MeSH secundário: Técnicas de Cultura de Células
Proliferação Celular/efeitos dos fármacos
Sobrevivência Celular/efeitos dos fármacos
Colo/metabolismo
Colo/patologia
Ensaio Cometa
Citometria de Fluxo
Células HT29
Seres Humanos
Mutagênicos/isolamento & purificação
Naftoquinonas/isolamento & purificação
Fase S/efeitos dos fármacos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Mutagens); 0 (Naphthoquinones); EYG3R23SI1 (aurofusarin)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180221
[Lr] Data última revisão:
180221
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171218
[St] Status:MEDLINE


  6 / 6543 MEDLINE  
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[PMID]:29217480
[Au] Autor:Aichinger G; Puntscher H; Beisl J; Kütt ML; Warth B; Marko D
[Ad] Endereço:Department of Food Chemistry and Toxicology, Faculty of Chemistry, University of Vienna, Waehringerstr. 38, A-1090 Vienna, Austria.
[Ti] Título:Delphinidin protects colon carcinoma cells against the genotoxic effects of the mycotoxin altertoxin II.
[So] Source:Toxicol Lett;284:136-142, 2018 Mar 01.
[Is] ISSN:1879-3169
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Alternaria spp. are ubiquitous molds that are able to produce toxic secondary metabolites which may contaminate food globally. One of those is the mycotoxin altertoxin II (ATX-II), a genotoxic and mutagenic compound. In recent years, different flavonoids that may co-occur with mycotoxins in food were demonstrated to temper toxic effects of molds, mostly through their anti-oxidant properties. Thus, in this study, we assessed the influence of the berry anthocyanidin delphinidin on the toxicity of ATX-II in HT-29 colon carcinoma cells. We performed coupled SRB/WST-1 cytotoxicity assays which revealed only weak antagonistic interactions, and single-cell gel electrophoresis ("comet") assays, where we observed a potent protective effect of delphinidin on the DNA-damaging properties of ATX-II. Furthermore, we investigated the mechanism for this interaction. In the DCF assay delphinidin was found to reduce intracellular oxidative stress levels, which might contribute partly to the latter protection. However, LC-MS experiments showed that co-incubation of the mycotoxin with either delphinidin or its potential degradation product phloroglucinol aldehyde significantly decreased ATX-II concentrations in aqueous solutions, indicating that a direct chemical reaction of ATX-II with these components is likely responsible for the observed loss of toxicity. Our results indicate that delphinidin - and possibly other anthocyanins as well - might play a role in the protection of the gut from Alternaria-induced genotoxicity.
[Mh] Termos MeSH primário: Antocianinas/farmacologia
Antioxidantes/farmacologia
Benzo(a)Antracenos/toxicidade
Dano ao DNA/efeitos dos fármacos
Mutagênicos/toxicidade
[Mh] Termos MeSH secundário: Alternaria/crescimento & desenvolvimento
Alternaria/metabolismo
Benzo(a)Antracenos/isolamento & purificação
Contagem de Células
Técnicas de Cultura de Células
Sobrevivência Celular/efeitos dos fármacos
Ensaio Cometa
Relação Dose-Resposta a Droga
Microbiologia de Alimentos
Células HT29
Seres Humanos
Estrutura Molecular
Mutagênicos/isolamento & purificação
Estresse Oxidativo/efeitos dos fármacos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anthocyanins); 0 (Antioxidants); 0 (Benz(a)Anthracenes); 0 (Mutagens); 56257-59-1 (altertoxin II); EM6MD4AEHE (delphinidin)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180221
[Lr] Data última revisão:
180221
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171209
[St] Status:MEDLINE


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[PMID]:29287997
[Au] Autor:Machado KDC; Sousa LQ; Lima DJB; Soares BM; Cavalcanti BC; Maranhão SS; Noronha JDC; Rodrigues DJ; Militão GCG; Chaves MH; Vieira-Júnior GM; Pessoa C; Moraes MO; Sousa JMCE; Melo-Cavalcante AAC; Ferreira PMP
[Ad] Endereço:Postgraduate Program in Pharmaceutical Sciences, Federal University of Piauí, Teresina, Brazil.
[Ti] Título:Marinobufagin, a molecule from poisonous frogs, causes biochemical, morphological and cell cycle changes in human neoplasms and vegetal cells.
[So] Source:Toxicol Lett;285:121-131, 2018 Mar 15.
[Is] ISSN:1879-3169
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Skin toad secretion present physiologically active molecules to protect them against microorganisms, predators and infections. This work detailed the antiproliferative action of marinobufagin on tumor and normal lines, investigate its mechanism on HL-60 leukemia cells and its toxic effects on Allium cepa meristematic cells. Initially, cytotoxic action was assessed by colorimetric assays. Next, HL-60 cells were analyzed by morphological and flow cytometry techniques and growing A. cepa roots were examined after 72 h exposure. Marinobufagin presented high antiproliferative action against all human tumor lines [IC values ranging from 0.15 (leukemia) to 7.35 (larynx) µM] and it failed against human erythrocytes and murine lines. Human normal peripheral blood mononuclear cells (PBMC) were up to 72.5-fold less sensitive [IC 10.88 µM] to marinobufagin than HL-60 line, but DNA strand breaks were no detected. Leukemia treaded cells exhibited cell viability reduction, DNA fragmentation, phosphatidylserine externalization, binucleation, nuclear condensation and cytoplasmic vacuoles. Marinobufagin also reduced the growth of A. cepa roots (EC : 7.5 µM) and mitotic index, caused cell cycle arrest and chromosomal alterations (micronuclei, delays and C-metaphases) in meristematic cells. So, to find out partially targeted natural molecules on human leukemia cells, like marinobufagin, is an amazing and stimulating way to continue the battle against cancer.
[Mh] Termos MeSH primário: Antineoplásicos/farmacologia
Bufanolídeos/farmacologia
Ciclo Celular/efeitos dos fármacos
Quebras de DNA
Cebolas/efeitos dos fármacos
[Mh] Termos MeSH secundário: Adolescente
Adulto
Animais
Antineoplásicos/isolamento & purificação
Antineoplásicos/toxicidade
Bufanolídeos/isolamento & purificação
Bufanolídeos/toxicidade
Bufonidae/metabolismo
Sobrevivência Celular/efeitos dos fármacos
Ensaio Cometa
Relação Dose-Resposta a Droga
Eritrócitos/efeitos dos fármacos
Células HL-60
Voluntários Saudáveis
Hemólise/efeitos dos fármacos
Seres Humanos
Leucócitos Mononucleares/efeitos dos fármacos
Meristema/citologia
Meristema/efeitos dos fármacos
Meristema/genética
Micronúcleos com Defeito Cromossômico/induzido quimicamente
Cebolas/citologia
Cebolas/genética
Pele/secreção
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antineoplastic Agents); 0 (Bufanolides); 3KBT25GV2B (marinobufagenin)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180219
[Lr] Data última revisão:
180219
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171231
[St] Status:MEDLINE


  8 / 6543 MEDLINE  
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[PMID]:29431060
[Au] Autor:Goldoni A; Klauck CR; Puffal J; Ardenghi PG; da Silva LB
[Ad] Endereço:Grupo de Pesquisa em Indicadores de Qualidade Ambiental, Universidade Feevale, Novo Hamburgo, RS, Brasil.
[Ti] Título:DNA Damage in Wistar Rats Exposed to Organophosphate Pesticide Fenthion.
[So] Source:J Environ Pathol Toxicol Oncol;36(4):277-281, 2017.
[Is] ISSN:2162-6537
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:In the last several decades, exposure to pesticides has become a concern to environmental and human health. Many pesticides are environmentally persistent and are characterized by varying degrees of toxicity and adverse effects, including DNA damage. The present study was undertaken to evaluate the genotoxic potential of organophosphate pesticide fenthion in Wistar rats, as assessed by the comet assay. Adult male Wistar rats were treated with a solution of fenthion at a concentration of 40 mg/kg/day, administered intraperitoneally for 18 consecutive days. Rats were killed 24 hours after the last pesticide administration, and the comet assay was performed in peripheral blood cells. The comet assay results revealed that the damage index (19.29 ± 3.59 vs. 7.80 ± 2.25) and the damage frequency (17.00 ± 3.46 vs. 7.5 ± 2.46) found in fenthion-treated rats were significantly higher than those found in the control group (p = 0.001 and p = 0.0006, respectively). The results show that fenthion affects the DNA integrity of rat cells and may induce DNA damage in exposed organisms.
[Mh] Termos MeSH primário: Dano ao DNA
Fention/toxicidade
Inseticidas/toxicidade
[Mh] Termos MeSH secundário: Animais
Ensaio Cometa
Masculino
Ratos
Ratos Wistar
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Insecticides); BL0L45OVKT (Fenthion)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180216
[Lr] Data última revisão:
180216
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180213
[St] Status:MEDLINE
[do] DOI:10.1615/JEnvironPatholToxicolOncol.2017024241


  9 / 6543 MEDLINE  
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[PMID]:29329665
[Au] Autor:Wang Y; Yu YX; Luan Y; An J; Yin DG; Zhang XY
[Ad] Endereço:School of Environmental and Chemical Engineering, Shanghai University, Shanghai 200444, China.
[Ti] Título:Bioactivation of 1-chloro-2-hydroxy-3-butene, an in vitro metabolite of 1,3-butadiene, by rat liver microsomes.
[So] Source:Chem Biol Interact;282:36-44, 2018 Feb 25.
[Is] ISSN:1872-7786
[Cp] País de publicação:Ireland
[La] Idioma:eng
[Ab] Resumo:1-Chloro-2-hydroxy-3-butene (CHB) is an in vitro metabolite of 1,3-butadiene, a rodent/human carcinogen. To search for an approach detecting CHB in vivo, it is vital to obtain a full understanding of CHB metabolism. Previously, we demonstrated that CHB was bioactivated to 1-chloro-3-buten-2-one (CBO) by alcohol dehydrogenase. However, CHB metabolism by cytochrome P450s has not been reported. Thus, in the present study, CHB metabolism by rat liver microsomes was investigated. The results showed that CHB was converted to 1-chloro-3,4-epoxy-2-butanol (CEB) and CBO. 4-Methylpyrazole, a cytochrome P450 2E1-specific inhibitor, inhibited the formation of both CEB and CBO, while 1-benzylimidazole, a generic cytochrome P450 inhibitor, completely abolished the formation of CEB and CBO, suggesting that CHB metabolism was mediated by cytochrome P450s. Because the molecules have two chiral centers, CEB was detected as two stereoisomers, which were designated D-CEB and M-CEB, and were characterized as (2S,3R)-/(2R,3S)-CEB and (2R,3R)-/(2S,3S)-CEB, respectively. The amounts of M-CEB were more than those of D-CEB by 50-80%. The amounts of CEB and CBO increased linearly over time from 10 (or 20 min for CBO) to 50 min. CHB metabolism followed Michaelis-Menten kinetics; the K and V values were determined to be 6.4 ±â€¯0.7 mM and 0.10 ±â€¯0.01 nmol/min/mg protein for D-CEB, 4.2 ±â€¯0.5 mM and 0.16 ±â€¯0.01 nmol/min/mg protein for M-CEB, and 4.0 ±â€¯0.5 mM and 4.6 ±â€¯0.5 nmol/min/mg protein for CBO, respectively. Thus, CBO was the dominant product of CHB metabolism. Moreover, CEB was genotoxic at ≥ 50 µM as evaluated by the comet assay. Collectively, the data showed that CHB could be bioactivated to CEB and CBO by cytochrome P450s with CBO being the predominant product. Thus, the formation of CEB and CBO can be used as evidence of CHB production. The products may also play a role in toxicity of CHB.
[Mh] Termos MeSH primário: Butadienos/metabolismo
Butanóis/metabolismo
Microssomos Hepáticos/metabolismo
[Mh] Termos MeSH secundário: Animais
Carcinógenos/metabolismo
Ensaio Cometa/métodos
Sistema Enzimático do Citocromo P-450/metabolismo
Ratos
Ratos Sprague-Dawley
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Butadienes); 0 (Butanols); 0 (Carcinogens); 671-56-7 (1-chloro-2-hydroxy-3-butene); 9035-51-2 (Cytochrome P-450 Enzyme System); JSD5FGP5VD (1,3-butadiene)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180209
[Lr] Data última revisão:
180209
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180114
[St] Status:MEDLINE


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[PMID]:28458013
[Au] Autor:Wang S; He Z; Li D; Zhang B; Li M; Li W; Zhu W; Xing X; Zeng X; Wang Q; Dong G; Xiao Y; Chen W; Chen L
[Ad] Endereço:Department of Toxicology, Guangzhou Key Laboratory of Environmental Pollution and Health Risk Assessment, School of Public Health, Sun Yat-sen University, Guangzhou, China.
[Ti] Título:Aberrant methylation of RUNX3 is present in Aflatoxin B -induced transformation of the L02R cell line.
[So] Source:Toxicology;385:1-9, 2017 06 15.
[Is] ISSN:1879-3185
[Cp] País de publicação:Ireland
[La] Idioma:eng
[Ab] Resumo:Chronic exposure to aflatoxin B (AFB ) is linked to the development of hepatocellular carcinoma (HCC). To identify differentially methylated genes involved in AFB -induced cell transformation, we analyzed DNA methylation patterns in immortal human hepatocyte L02 cells expressing an oncogenic H-Ras allele (L02R cells) and AFB -transformed L02R (L02RT-AFB ) cells by performing genome-wide methylation profiling. We treated L02R cells with 0.3µM AFB weekly and observed a transformed phenotype at the 17th week post-treatment. The transformed cells (L02RT-AFB ) could grow in an anchorage independent fashion and form tumors in immunodeficient mice. qRT-PCR was performed to examine whether gene methylation led to a reduction in gene expression of methylated candidate genes. As a result, the expression of the following seven genes including JUNB, RUNX3, NAV1, CXCR4, RARRES1, INTS1, and POLL was down-regulated in transformed L02RT-AFB cells. The reduction of gene expression of these genes could be reversed by treatment of 5-azadeoxycytidine. The methylated CpG sites of RUNX3 genes were verified using bisulfite sequencing PCR (BSP) assay. Furthermore, a dynamic change in RUNX3 methylation was observed over the course of AFB -induced cell transformation, which was corresponded to the alteration of gene expression and the extent of DNA damage. In vitro study showed that methylation of RUNX3 tended to abate in L02R cells treated with AFB for a short-term period of time. Notably, hypermethylation of RUNX3 appeared in 70% (14/20) of human hepatocellular carcinomas. Moreover, LINE-1 hypomethylation and dynamic changes of DNMTs, TETs and MeCP2 expression were also observed during AFB -induced transformation. Taken together, these observations suggest that aberrant methylation of RUNX3 and LINE-1 might be involved in AFB -induced carcinogenesis.
[Mh] Termos MeSH primário: Carcinoma Hepatocelular/genética
Transformação Celular Neoplásica/genética
Subunidade alfa 3 de Fator de Ligação ao Core/genética
Neoplasias Hepáticas/genética
[Mh] Termos MeSH secundário: Adulto
Aflatoxina B1
Carcinoma Hepatocelular/metabolismo
Linhagem Celular
Ensaio Cometa
Subunidade alfa 3 de Fator de Ligação ao Core/metabolismo
Metilação de DNA
Desoxirribonuclease I/genética
Feminino
Seres Humanos
Neoplasias Hepáticas/metabolismo
Masculino
Meia-Idade
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Core Binding Factor Alpha 3 Subunit); 0 (Runx3 protein, human); 9N2N2Y55MH (Aflatoxin B1); EC 3.1.21.1 (Deoxyribonuclease I); EC 3.1.21.1 (LINE-1 endonuclease, human)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:180122
[Lr] Data última revisão:
180122
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170502
[St] Status:MEDLINE



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