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Pesquisa : A11.284.430.106.570 [Categoria DeCS]
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[PMID]:29424501
[Au] Autor:Reutova NV; Dreeva FR; Reutova TV; Shevchenko AV; Dudarov ZI
[Ti] Título:[Effect of recultivated wastes of mining factories on children residing in the district of their location].
[So] Source:Gig Sanit;95(6):572-6, 2016.
[Is] ISSN:0016-9900
[Cp] País de publicação:Russia (Federation)
[La] Idioma:rus
[Ab] Resumo:Wastes and tailing ponds of Tyrnyauz tungsten and molybdenum factory are the main sources of heavy metal incoming into environment in Kabardino-Balkarian Republic. The factory was closed more than 10 years ago and the recultivation of it's tailing ponds, where accumulated hundreds of millions tones of wastes, was completed. The aim of this investigation was an assessment of their possible influence on children residing in the vicinity of these tailing ponds (village Bylym). Village Verhny Baksan located about 30 km upstream of the valley of the Baksan River was chosen as reference (pure) locality. As a results of the performed investigations we revealed that in drinking water of Bylym and Verhny Baksan concentrations of molybdenum were 2.10±0.42 pg/l and 0.31±0.15 pg/l correspondingly, which is remarkably lower than maximum permitted concentrations. The concentrations of Mo, Cu and Pb in children's hair in both villages were practically the same, which indicates to the absence of their accumulation in human organism. But the quantity of cells with cytogenetic disorders in buccal epithelial cells in children from Bylym was 4.1 times higher in comparison with the corresponding index of uncontaminated area. The obtained data demonstrate that genotoxic effect of remedied tailing ponds retains.
[Mh] Termos MeSH primário: Exposição Ambiental
Cabelo/química
Metais Pesados
Micronúcleos com Defeito Cromossômico/induzido quimicamente
Mineração
Poluentes do Solo
Instalações de Eliminação de Resíduos/normas
Poluentes Químicos da Água
[Mh] Termos MeSH secundário: Criança
Exposição Ambiental/efeitos adversos
Exposição Ambiental/análise
Exposição Ambiental/prevenção & controle
Monitoramento Ambiental/métodos
Monitoramento Ambiental/estatística & dados numéricos
Feminino
Seres Humanos
Masculino
Metais Pesados/análise
Metais Pesados/normas
Mineração/métodos
Mineração/normas
Mucosa Bucal/patologia
Federação Russa/epidemiologia
Poluentes do Solo/análise
Poluentes do Solo/normas
Poluentes Químicos da Água/análise
Poluentes Químicos da Água/normas
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Metals, Heavy); 0 (Soil Pollutants); 0 (Water Pollutants, Chemical)
[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:180210
[St] Status:MEDLINE


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[PMID]:29391062
[Au] Autor:Lee MY; Park YC; Jin M; Kim E; Choi JJ; Jung IC
[Ad] Endereço:Genogen Co., Ltd, Room 402, 125, Osongsaengmyeong 2-ro, Osong-eup, Heungdeok-gu, Cheongju-si, Chungcheongbuk-do, 28161, Republic of Korea.
[Ti] Título:Genotoxicity evaluation of So-ochim-tang-gamibang (SOCG), a herbal medicine.
[So] Source:BMC Complement Altern Med;18(1):47, 2018 Feb 02.
[Is] ISSN:1472-6882
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: So-ochim-tang-gamibang (SOCG) is a traditional Korean medicine frequently used for depression in the clinical field. In this study, we evaluated the potential genotoxicity of SOCG using three standard batteries of tests as part of a safety evaluation. METHODS: SOCG was evaluated for potential genotoxic effects using the standard three tests recommended by the Ministry of Food and Drug Safety (MFDS) of Korea. These tests were the bacterial reverse mutation test (Ames test), in vitro mammalian chromosomal aberration test using Chinese hamster lung cells, and in vivo micronucleus test using ICR mice. RESULTS: The Ames test with Salmonella typhimurium strains TA98, TA100, TA1535 and TA1537 and the Escherichia coli strain WP2uvrA(pKM101) showed that SOCG did not induce gene mutations at any dose level in all of the strains. SOCG did not induce any chromosomal aberrations in the in vitro chromosomal aberration test (for both the 6 and 24 h test) and the in vivo micronucleus test. CONCLUSIONS: Based on the results of these tests, it was concluded that SOCG does not exhibit any genotoxic risk under the experimental conditions of this study.
[Mh] Termos MeSH primário: Mutagênicos/toxicidade
Extratos Vegetais/toxicidade
[Mh] Termos MeSH secundário: Animais
Linhagem Celular
Aberrações Cromossômicas/efeitos dos fármacos
Cricetinae
Cricetulus
Escherichia coli/efeitos dos fármacos
Masculino
Medicina Tradicional Coreana
Camundongos
Camundongos Endogâmicos ICR
Micronúcleos com Defeito Cromossômico/efeitos dos fármacos
Testes para Micronúcleos
Testes de Mutagenicidade
Salmonella typhimurium/efeitos dos fármacos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Mutagens); 0 (Plant Extracts); 0 (so-ochim-tang-gamibang)
[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/s12906-018-2111-2


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[PMID]:28749179
[Au] Autor:Feng NN; Fang Y; Zhang YN; Xu XW; Li Y; Wang JW; Li YL; Brandt-Rauf P; Xia ZL
[Ad] Endereço:Department of Occupational Health & Toxicology, School of Public Health, Fudan University, & Key Laboratory of Public Health & Safety of Ministry of Education of China, Shanghai, 200032, China.
[Ti] Título:Analysis of microRNA expression and micronuclei frequency in workers exposed to vinyl chloride monomer in China.
[So] Source:Epigenomics;9(8):1093-1104, 2017 Aug.
[Is] ISSN:1750-192X
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:AIM: To identify differently expressed miRNAs associated with vinyl chloride monomer (VCM) and micronuclei (MN) frequency. METHOD: In discovery stage, we used microarray to detect miRNAs expression in peripheral blood lymphocytes between six low and six high VCM-exposed workers grouped by medium cumulative exposure dose. Then we validated four miRNAs using real-time quantitative reverse transcription PCR (qRT-PCR) and detected the micronuclei frequencies using cytokinesis-block micronucleus assay in 94 VCM-exposed workers and 53 healthy control subjects. RESULTS & CONCLUSION: We found eight miRNAs significantly downregulated and seven miRNAs upregulated (|Fold Change| >2; p < 0.05) in the high-exposure group through microarray. We validate that miR-222-3p, miR-146a-5p and miR-151a-5p were downregulated, while miR-22-3p was upregulated in VCM-exposed group (all p < 0.01). Furthermore, we found that expression of miR-22-3p was upregulated in the high micronuclei (MN) frequency subjects. In conclusion, our study suggested that these four miRNAs could be biomarkers of VCM exposure, and moreover miR-22-3p was correlated with MN frequency.
[Mh] Termos MeSH primário: Indústria Química
MicroRNAs/genética
Micronúcleos com Defeito Cromossômico/estatística & dados numéricos
Exposição Ocupacional/efeitos adversos
Cloreto de Vinil/toxicidade
[Mh] Termos MeSH secundário: Adulto
Estudos de Casos e Controles
China
Feminino
Seres Humanos
Masculino
Micronúcleos com Defeito Cromossômico/induzido quimicamente
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (MicroRNAs); WD06X94M2D (Vinyl Chloride)
[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:170728
[St] Status:MEDLINE
[do] DOI:10.2217/epi-2017-0028


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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


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[PMID]:28461331
[Au] Autor:Head PE; Zhang H; Bastien AJ; Koyen AE; Withers AE; Daddacha WB; Cheng X; Yu DS
[Ad] Endereço:From the Departments of Radiation Oncology and.
[Ti] Título:Sirtuin 2 mutations in human cancers impair its function in genome maintenance.
[So] Source:J Biol Chem;292(24):9919-9931, 2017 06 16.
[Is] ISSN:1083-351X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Sirtuin 2 (SIRT2) is a sirtuin family deacetylase, which maintains genome integrity and prevents tumorigenesis. Although deficiency in mice leads to tumorigenesis, the functional significance of somatic mutations in human tumors is unclear. Using structural insight combined with bioinformatics and functional analyses, we show that naturally occurring cancer-associated mutations at evolutionarily conserved sites disrupt its deacetylation of DNA-damage response proteins by impairing SIRT2 catalytic activity or protein levels but not its localization or binding with substrate. We observed that these SIRT2 mutant proteins fail to restore the replication stress sensitivity, impairment in recovery from replication stress, and impairment in ATR-interacting protein (ATRIP) focus accumulation of deficiency. Moreover, the SIRT2 mutant proteins failed to rescue the spontaneous induction of DNA damage and micronuclei of deficiency in cancer cells. Our findings support a model for SIRT2's tumor-suppressive function in which somatic mutations in contribute to genomic instability by impairing its deacetylase activity or diminishing its protein levels in the DNA-damage response. In conclusion, our work provides a mechanistic basis for understanding the biological and clinical significance of mutations in genome maintenance and tumor suppression.
[Mh] Termos MeSH primário: Instabilidade Genômica
Modelos Moleculares
Mutação
Proteínas de Neoplasias/metabolismo
Neoplasias/metabolismo
Sirtuína 2/metabolismo
[Mh] Termos MeSH secundário: Acetilação
Sequência de Aminoácidos
Substituição de Aminoácidos
Biocatálise
Linhagem Celular
Biologia Computacional
Sequência Conservada
Reparo do DNA
Bases de Dados Genéticas
Regulação Neoplásica da Expressão Gênica
Seres Humanos
Micronúcleos com Defeito Cromossômico
Mutação de Sentido Incorreto
Proteínas de Neoplasias/antagonistas & inibidores
Proteínas de Neoplasias/química
Proteínas de Neoplasias/genética
Neoplasias/genética
Neoplasias/patologia
Conformação Proteica
Interferência de RNA
Proteínas Recombinantes de Fusão/química
Proteínas Recombinantes de Fusão/metabolismo
Sirtuína 2/antagonistas & inibidores
Sirtuína 2/química
Sirtuína 2/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Neoplasm Proteins); 0 (Recombinant Fusion Proteins); EC 3.5.1.- (SIRT2 protein, human); EC 3.5.1.- (Sirtuin 2)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:171228
[Lr] Data última revisão:
171228
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170503
[St] Status:MEDLINE
[do] DOI:10.1074/jbc.M116.772566


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[PMID]:27770565
[Au] Autor:Xia Q; Li H; Liu Y; Zhang S; Feng Q; Xiao K
[Ad] Endereço:National Chengdu Center for Safety Evaluation of Drugs, State Key Laboratory of Biotherapy, Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, People's Republic of China.
[Ti] Título:The effect of particle size on the genotoxicity of gold nanoparticles.
[So] Source:J Biomed Mater Res A;105(3):710-719, 2017 03.
[Is] ISSN:1552-4965
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Despite the increasing biomedical applications of gold nanoparticles (AuNPs), their toxicological effects need to be thoroughly understood. In the present study, the genotoxic potential of commercially available AuNPs with varying size (5, 20, and 50 nm) were assessed using a battery of in vitro and in vivo genotoxicity assays. In the comet assay, 20 and 50 nm AuNPs did not induce obvious DNA damage in HepG2 cells at the tested concentrations, whereas 5 nm NPs induced a dose-dependent increment in DNA damage after 24-h exposure. Furthermore, 5 nm AuNPs induced cell cycle arrest in G1 phase in response to DNA damage, and promoted the production of reactive oxygen species (ROS). In the chromosomal aberration test, AuNPs exposure did not increase in the frequency of chromosomal aberrations in Chinese hamster lung (CHL) cells. In the standard in vivo micronucleus test, no obvious increase in the frequency of micronucleus formation was found in mice after 4 day exposure of AuNPs. However, when the exposure period was extended to 14 days, 5 nm AuNPs presented significant clastogenic damage, with a dose-dependent increase of micronuclei frequencies. This finding suggests that particle size plays an important role in determining the genotoxicity of AuNPs. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 710-719, 2017.
[Mh] Termos MeSH primário: Dano ao DNA
Pontos de Checagem da Fase G1 do Ciclo Celular/efeitos dos fármacos
Ouro
Nanopartículas Metálicas
Micronúcleos com Defeito Cromossômico
[Mh] Termos MeSH secundário: Animais
Relação Dose-Resposta a Droga
Ouro/efeitos adversos
Ouro/química
Ouro/farmacologia
Células Hep G2
Seres Humanos
Nanopartículas Metálicas/efeitos adversos
Nanopartículas Metálicas/química
Camundongos
Tamanho da Partícula
Fatores de Tempo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
7440-57-5 (Gold)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171225
[Lr] Data última revisão:
171225
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161023
[St] Status:MEDLINE
[do] DOI:10.1002/jbm.a.35944


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[PMID]:28456919
[Au] Autor:Aslantürk ÖS; Askin Çelik T
[Ad] Endereço:Faculty of Art and Science, Department of Biology, Adnan Menderes University, 09010, Aydin, Turkey.
[Ti] Título:Genotoxic risk assessment in professionals working hairdressers area using buccal micronucleus assay, in Aydin City, Turkey.
[So] Source:Environ Sci Pollut Res Int;24(17):14700-14705, 2017 Jun.
[Is] ISSN:1614-7499
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:The aim of this study was to determine the genotoxic risk of professional hairdressers in Aydin City, Turkey, through investigating the micronucleus frequencies in buccal mucosa epithelial cells. All the hairdresser working hairdresser area were included in the genotoxic risk group (GRG = 20) in Aydin City, Turkey. The control group (CG = 20) comprised healthy individuals matching the gender and age of the GRG. Buccal mucosal scraping from all the 40 subjects of GRG (10 women and 10 men) and CG (10 women and 10 men) was stained with Giemsa stain and observed under light microscope (×40) for the presence of micronuclei (M 10 N) and karyolysis, pyknosis, condensed chromatin, karyorrhexis, nuclear bud, and binucleates in the exfoliated epithelial cells. There are significance between the incidence of MN in GRG and CG (P = <0.005) using one-way ANOVA, Kolmogorov-Smirnov Z test, and Spearman Rank Correlation Tests.
[Mh] Termos MeSH primário: Dano ao DNA
Preparações para Cabelo
Exposição Ocupacional
Medição de Risco
[Mh] Termos MeSH secundário: Adulto
Estudos de Casos e Controles
Feminino
Seres Humanos
Masculino
Micronúcleos com Defeito Cromossômico
Testes para Micronúcleos
Mucosa Bucal
Turquia
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Hair Preparations)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:171215
[Lr] Data última revisão:
171215
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170501
[St] Status:MEDLINE
[do] DOI:10.1007/s11356-017-9075-5


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[PMID]:28985345
[Au] Autor:Venkatachalam G; Surana U; Clément MV
[Ad] Endereço:Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117596, Singapore.
[Ti] Título:Replication stress-induced endogenous DNA damage drives cellular senescence induced by a sub-lethal oxidative stress.
[So] Source:Nucleic Acids Res;45(18):10564-10582, 2017 Oct 13.
[Is] ISSN:1362-4962
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Although oxidative stress has been shown to induce senescence and replication stress independently, no study has implicated unresolved replication stress as the driver for cellular senescence in response to oxidative stress. Using cells exposed to increasing concentrations of hydrogen peroxide, we show that sub-lethal amount of exogenous hydrogen peroxide induces two waves of DNA damage. The first wave is rapid and transient while the second wave coincides with the cells transition from the S to the G2/M phases of cell cycle. Subsequently, cells enter growth arrest accompanied by the acquisition of senescence-associated characteristics. Furthermore, a p53-dependent decrease in Rad51, which is associated with the formation of DNA segments with chromatin alterations reinforcing senescence, and Lamin B1 that is involved in chromatin remodeling, is observed during the establishment of the senescent phenotype. On the other hand, increase in senescence associated-ß-Gal activity, a classical marker of senescence and HMGA2, a marker of the senescence-associated heterochromatin foci, is shown to be independent of p53. Together, our findings implicate replication stress-induced endogenous DNA damage as the driver for the establishment of cellular senescence upon sub-lethal oxidative stress, and implicate the role of p53 in some but not all hallmarks of the senescent phenotype.
[Mh] Termos MeSH primário: Senescência Celular/genética
Dano ao DNA
Replicação do DNA
Estresse Oxidativo/genética
[Mh] Termos MeSH secundário: Animais
Linhagem Celular
Quebras de DNA de Cadeia Dupla
Quebras de DNA de Cadeia Simples
Proteína HMGA2/metabolismo
Histonas/metabolismo
Lamina Tipo B/metabolismo
Micronúcleos com Defeito Cromossômico
Rad51 Recombinase/metabolismo
Ratos
Proteína Supressora de Tumor p53/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (HMGA2 Protein); 0 (Histones); 0 (Lamin Type B); 0 (Tumor Suppressor Protein p53); 0 (lamin B1); EC 2.7.7.- (Rad51 Recombinase)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171007
[St] Status:MEDLINE
[do] DOI:10.1093/nar/gkx684


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[PMID]:28943391
[Au] Autor:García-Niño WR; Estrada-Muñiz E; Valverde M; Reyes-Chilpa R; Vega L
[Ad] Endereço:Department of Toxicology, Centre for Research and Advanced Studies of the National Polytechnic Institute (CINVESTAV-IPN), Av. IPN 2508, San Pedro Zacatenco, GA Madero, Ciudad de México, CP 07360, Mexico.
[Ti] Título:Cytogenetic effects of Jacareubin from Calophyllum brasiliense on human peripheral blood mononucleated cells in vitro and on mouse polychromatic erythrocytes in vivo.
[So] Source:Toxicol Appl Pharmacol;335:6-15, 2017 Nov 15.
[Is] ISSN:1096-0333
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Jacareubin is a xanthone isolated from the heartwood of Calophyllum brasiliense with antibacterial and gastroprotective properties and the intention for clinical use as an anti-cancer treatment (due to the similar chemical structure to other anti-neoplastic drugs) requires an investigation of whether this compound can generate adverse effects on non-transformed cells. Jacareubin (0.5-1000µM in DMSO) was more cytotoxic on phytohemagglutinin (PHA)-stimulated normal human peripheral blood mononuclear cells (PBMCs; IC at 72h by MTT: 85.9µM) than on G phase-PBMCs (IC 315.6µM) using trypan blue exclusion and formazan metabolism assays. Jacareubin had lower toxicity on PBMCs than Taxol (1µM). Jacareubin presented cytostatic activity because it inhibited PHA-stimulated PBMCs proliferation (from 2.5µM; CFSE dilution and replication index). Jacareubin induced PBMCs arrest in G /G phase of the cell cycle (from 5µM) as evaluated by DNA content. Moreover, Jacareubin generated genotoxicity by breaking DNA strands selectively in PHA-stimulated PBMCs (from 5µM) rather than on resting PBMCs using the single-cell gel electrophoresis assay and increasing the frequency of micronucleated (MN) PBMCs in vitro (from 5µM) and frequency of hypodiploid cells (from 10µM). When 100mg/kg Jacareubin was injected i.p. into mice (a fifth of the LD ; 0.548g/kg. Approximately to 300µM in vitro), we observe no increase in the MN level in bone marrow cells. Jacareubin can be consider for further anti-tumoural activity due to its preferential genotoxic, cytotoxic and cytostatic actions on proliferating cells rather than on resting cells and the lack of in vivo genotoxicity.
[Mh] Termos MeSH primário: Antineoplásicos Fitogênicos/farmacologia
Calophyllum/química
Dano ao DNA
Eritrócitos/efeitos dos fármacos
Leucócitos Mononucleares/efeitos dos fármacos
Extratos Vegetais/farmacologia
Xantonas/farmacologia
[Mh] Termos MeSH secundário: Adulto
Aneuploidia
Animais
Antineoplásicos Fitogênicos/isolamento & purificação
Antineoplásicos Fitogênicos/toxicidade
Pontos de Checagem do Ciclo Celular/efeitos dos fármacos
Morte Celular/efeitos dos fármacos
Proliferação Celular/efeitos dos fármacos
Sobrevivência Celular/efeitos dos fármacos
Células Cultivadas
Relação Dose-Resposta a Droga
Eritrócitos/patologia
Seres Humanos
Concentração Inibidora 50
Leucócitos Mononucleares/patologia
Masculino
Camundongos Endogâmicos BALB C
Micronúcleos com Defeito Cromossômico/induzido quimicamente
Extratos Vegetais/isolamento & purificação
Extratos Vegetais/toxicidade
Medição de Risco
Fatores de Tempo
Xantonas/isolamento & purificação
Xantonas/toxicidade
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antineoplastic Agents, Phytogenic); 0 (Plant Extracts); 0 (Xanthones); 0 (jacareubin)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171025
[Lr] Data última revisão:
171025
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170926
[St] Status:MEDLINE


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[PMID]:28923333
[Au] Autor:Cuello-Almarales DA; Almaguer-Mederos LE; Vázquez-Mojena Y; Almaguer-Gotay D; Zayas-Feria P; Laffita-Mesa JM; González-Zaldívar Y; Aguilera-Rodríguez R; Rodríguez-Estupiñán A; Velázquez-Pérez L
[Ad] Endereço:Department of Molecular Biology, Center for Research and Rehabilitation of Hereditary Ataxias (CIRAH), Holguín City, Cuba. Electronic address: cuellodany@gmail.com.
[Ti] Título:Buccal Cell Micronucleus Frequency Is Significantly Elevated in Patients with Spinocerebellar Ataxia Type 2.
[So] Source:Arch Med Res;48(3):297-302, 2017 Apr.
[Is] ISSN:1873-5487
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Spinocerebellar ataxia type 2 (SCA2) is part of a group of at least nine dominantly inherited disorders characterized by progressive degeneration of specific neuronal populations and a shared mutational mechanism involving the expansion of a CAG repeat tract in coding regions of novel genes. Efforts have been made to identify biomarkers of disease progression, which would allow timely preventive therapeutic interventions. In the present study was assessed the influence of several genome instability biomarkers on SCA2 clinical severity. A case-control design was applied on exfoliated epithelial buccal cells to determine micronuclei frequency and others nuclear anomalies, using 5% Giemsa stains. The slides were analyzed under 1000X magnification and nuclei morphological anomalies were identified according to Tolbert PE, et al. (1992) and Bolognesi C, et al. (2013) criteria. It was found a highly significant increase in micronuclei frequency in cases related to age and sex-matched healthy controls (p <0.001). There was a trend for karyolytic, pyknotic and condensed chromatin cells to be increased in SCA2 cases, and a significant association was found between binucleated cells and disease duration (r = 0.46; p = 0.027). Nor the CAG repeat length neither the age at onset correlated significantly with any of the studied markers (p >0.05). Our results are consistent with report previous in similar neurodegenerative diseases, and suggest that micronuclei and binucleated cells constitute potential peripheral biomarkers for SCA2. These results should be validated by other studies.
[Mh] Termos MeSH primário: Micronúcleos com Defeito Cromossômico
Mucosa Bucal/ultraestrutura
Ataxias Espinocerebelares/patologia
[Mh] Termos MeSH secundário: Adulto
Idade de Início
Estudos de Casos e Controles
Progressão da Doença
Feminino
Instabilidade Genômica
Seres Humanos
Masculino
Testes para Micronúcleos
Meia-Idade
Mutação
Ataxias Espinocerebelares/genética
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171023
[Lr] Data última revisão:
171023
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170920
[St] Status:MEDLINE



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