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The European Society for Medical Oncology (ESMO) Clinical Practice Guidelines for the diagnosis, treatment and follow-up of patients with early breast cancer were updated and published online in 2023, and adapted, according to previously established standard methodology, to produce the Pan-Asian adapted (PAGA) ESMO consensus guidelines for the management of Asian patients with early breast cancer. The adapted guidelines presented in this manuscript represent the consensus opinions reached by a panel of Asian experts in the treatment of patients with breast cancer representing the oncological societies of China (CSCO), Indonesia (ISHMO), India (ISMPO), Japan (JSMO), Korea (KSMO), Malaysia (MOS), the Philippines (PSMO), Singapore (SSO), Taiwan (TOS) and Thailand (TSCO), co-ordinated by ESMO and KSMO. The voting was based on scientific evidence and was independent of the current treatment practices, drug access restrictions and reimbursement decisions in the different Asian regions represented by the 10 oncological societies. The latter are discussed separately in the manuscript. The aim is to provide guidance for the optimisation and harmonisation of the management of patients with early breast cancer across the different regions of Asia, drawing on the evidence provided by both Western and Asian trials, whilst respecting the differences in screening practices, molecular profiling, as well as the age and stage at presentation. Attention is drawn to the disparity in the drug approvals and reimbursement strategies, between the different regions of Asia.
Assuntos
Neoplasias da Mama , Humanos , Neoplasias da Mama/terapia , Neoplasias da Mama/diagnóstico , Feminino , Ásia/epidemiologia , Oncologia/normas , Guias de Prática Clínica como Assunto , Estadiamento de NeoplasiasRESUMO
The inclusive electron neutrino charged-current cross section is measured in the NOvA near detector using 8.02×10^{20} protons-on-target in the NuMI beam. The sample of GeV electron neutrino interactions is the largest analyzed to date and is limited by ≃17% systematic rather than the ≃7.4% statistical uncertainties. The double-differential cross section in final-state electron energy and angle is presented for the first time, together with the single-differential dependence on Q^{2} (squared four-momentum transfer) and energy, in the range 1 GeV≤E_{ν}<6 GeV. Detailed comparisons are made to the predictions of the GENIE, GiBUU, NEUT, and NuWro neutrino event generators. The data do not strongly favor a model over the others consistently across all three cross sections measured, though some models have especially good or poor agreement in the single differential cross section vs Q^{2}.
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BACKGROUND: Primary breast lymphoma is a rare disease and accounts for 0.4-0.5% of malignant breast neoplasms and 1.7-2.2% of extra-nodal lymphomas, with diffuse large B-cell lymphoma (DLBCL) as the most common histologic subtype. CASE: A 47-year-old female with beta thalassemia presented with a lump of the left breast, redness, pain, and swelling of her left breast. Physical examination showed tender, red, swollen left breast. Laboratory findings show mild anemia and normal level of lactate dehydrogenase 329 U/L (normal range: 240-480 U/L). PET scan showed hypermetabolic mass with irregular margins covering the whole left breast quadrants with the size of 11.25 x 5.17cm with left pectoralis major, left parasternal, and left axillary hypermetabolic nodules. Histopathology and immunohistochemistry staining showed a non-germinal center B-cell-like subtype of DLBCL CD20+. We administered the R-CHOP regimen (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednison) every 3 weeks for 6 cycles. The response was complete remission. The patient tolerated the chemotherapy well and achieved long term complete remission. CONCLUSION: Primary breast lymphoma is a rare disease with the most common subtype is diffuse large B-cell lymphoma. Systemic chemother-apy R-CHOP is the treatment option for primary breast diffuse large B-cell lymphoma.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Neoplasias da Mama/diagnóstico por imagem , Ciclofosfamida/uso terapêutico , Doxorrubicina/uso terapêutico , Feminino , Humanos , Linfoma Difuso de Grandes Células B/diagnóstico por imagem , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons , Prednisona/uso terapêutico , Rituximab/uso terapêutico , Vincristina/uso terapêuticoRESUMO
Zinc oxide nanoparticles (ZnONP-GS) were synthesised from the precursor zinc acetate (Zn(CH3COO)2) through the green route using the milky latex from milk weed (Calotropis gigantea L. R. Br) by alkaline precipitation. Formation of the ZnONP-GS was monitored by UV-visible spectroscopy followed by characterization and confirmation by energy-dispersive X-ray spectroscopy (EDX), transmission electron microscopy (TEM), and X-ray diffraction (XRD). Both the ZnONP-GS and the commercially available ZnONP-S (Sigma-Aldrich) and cationic Zn2+ from Zn(CH3COO)2 were tested in a dose range of 0-100 mg·L-1 for their potency (i) to induce oxidative stress as measured by the generation reactive oxygen species (ROS: O2â¢-, H2O2 and â¢OH), cell death, and lipid peroxidation; (ii) to modulate the activities of antioxidant enzymes: catalase (CAT), superoxide dismutase (SOD), guaiacol peroxidase (GPX), and ascorbate peroxidase (APX); and (iii) to cause DNA damage as determined by Comet assay in Lathyrus sativus L. root bioassay system. Antioxidants such as Tiron and dimethylthiourea significantly attenuated the ZnONP-induced oxidative and DNA damage, suggesting the involvement of ROS therein. Our study demonstrated that both ZnONP-GS and ZnONP-S induced oxidative stress and DNA damage to a similar extent but were significantly less potent than Zn2+ alone.
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Meiotic recombination contributes to augmentation of genetic diversity, exclusion of deleterious alleles and proper segregation of chromatids. PRDM9 has been identified as the gene responsible for specifying the location of recombination hotspots during meiosis and is also the only known vertebrate gene associated with reproductive isolation between species. PRDM9 encodes a protein with a highly variable zinc finger (ZF) domain that varies between as well as within species. In the present study, the ZF domain of PRDM9 on chromosome 1 was characterized for the first time in 15 goat breeds and 25 sheep breeds of India. A remarkable variation in the number and sequence of ZF domains was observed. The number of ZF repeats in the ZF array varied from eight to 12 yielding five homozygous and 10 heterozygous genotypes. The number of different ZF domains was 84 and 52 producing 36 and 26 unique alleles in goats and sheep respectively. The posterior mean of dN/dS or omega values were calculated using the codeml tool of pamlx to identify amino acids that are evolving positively in goats and sheep, as positions -1, +3 and +6 in the ZF domain have been reported to experience strong positive selection across different lineages. Our study identified sites -5, -1, +3, +4 and +6 to be experiencing positive selection. Small ruminant zinc fingers were also found to be evolving under concerted evolution. Our results demonstrate the existence of a vast diversity of PRDM9 in goats and sheep, which is in concert with reports in many metazoans.
Assuntos
Evolução Molecular , Cabras/genética , Histona-Lisina N-Metiltransferase/genética , Seleção Genética , Carneiro Doméstico/genética , Dedos de Zinco/genética , Alelos , Sequência de Aminoácidos , Animais , Cruzamento , Genótipo , Índia , FilogeniaRESUMO
The silver nanoparticles (AgNPs) were synthesized extracellularly from silver nitrate (AgNO3) using kernel extract from ripe mango Mengifera indica L. under four different reaction conditions of the synthesis media such as the (i) absence of the reducing agent, trisodium citrate (AgNPI), (ii) presence of the reducing agent (AgNPII), (iii) presence of the cleansing agent, polyvinyl polypyrrolidone, PVPP (AgNPIII), and (iv) presence of the capping agent, polyvinyl pyrrolidone, PVP (AgNPIV). The synthesis of the AgNPs was monitored by UV-vis spectrophotometry. The AgNPs were characterised by the energy-dispersive X-ray spectroscopy, transmission electron microscopy, X-ray diffraction, and small-angle X-ray scattering. Functional groups on the AgNPs were established by the Fourier transform infrared spectroscopy. The AgNPs (AgNPI, AgNPII, AgNPIII and AgNPIV) were spherical in shape with the diameters and size distribution-widths of 14.0±5.4, 19.2±6.6, 18.8±6.6 and 44.6±13.2nm, respectively. Genotoxicity of the AgNPs at concentrations ranging from 1 to 100mgL(-1) was determined by the Lathyrus sativus L. root bioassay and several endpoint assays including the generation of reactive oxygen species and cell death, lipid peroxidation, mitotic index, chromosome aberrations (CA), micronucleus formation (MN), and DNA damage as determined by the Comet assay. The dose-dependent induction of genotoxicity of the silver ion (Ag(+)) and AgNPs was in the order Ag(+)>AgNPII>AgNPI>AgNPIV>AgNPIII that corresponded with their relative potencies of induction of DNA damage and oxidative stress. Furthermore, the findings underscored the CA and MN endpoint-based genotoxicity assay which demonstrated the genotoxicity of AgNPs at concentrations (≤10mgL(-1)) lower than that (≥10mgL(-1)) tested in the Comet assay. This study demonstrated the protective action of PVPP against the genotoxicity of AgNPIII which was independent of the size of the AgNPs in the L. sativus L. root bioassay system.
Assuntos
Lathyrus/efeitos dos fármacos , Mangifera/química , Nanopartículas Metálicas/química , Extratos Vegetais/química , Polivinil/farmacologia , Prata/toxicidade , Bioensaio , Aberrações Cromossômicas , Dano ao DNA/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Raízes de Plantas/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismoRESUMO
Disrupted meiotic cDNA1 (DMC1) recombinase plays a pivotal role in homology search and strand exchange reactions during meiotic homologous recombination. In the present study, full length coding sequence of DMC1 gene was sequence characterized for the first time from four ruminant species (cattle, buffalo, sheep and goat) and phylogenetic relationship of ruminant DMC1 with other eukaryotes was analyzed. DMC1 gene encodes a putative protein of 340 amino acids in cattle, sheep and buffalo and 341 amino acids in goat. A high degree of evolutionary conservation at both nucleotide and amino acid level was observed for the four ruminant orthologs. In cattle and sheep, novel alternatively spliced mRNAs with skipping of exons 7 and 8 (Transcript variant 1, TV1) were isolated in addition to the full length (FL) transcript. Novel transcript variants with partial skipping of exon 7 and complete skipping of exon 8 (Transcript variant 2, TV2) were found in sheep and goat. The presence of these variants was validated by amplifying cDNA isolated from testis tissue of ruminants using two oligonucleotides flanking the deleted region. To accurately estimate their relative proportions, real-time PCR was performed using primers specific for each variant. Expression level of DMC1-FL was significantly higher than that of TV1 in cattle and TV2 in goat (P < 0.05). Relative ratio for expression of DMC1-FL: TV1: TV2 in sheep was 6.78: 1.43: 1. In-silico analysis revealed presence of splice variants of DMC1 gene across other mammalian species underpinning the role of alternative splicing in functional innovation.
Assuntos
Processamento Alternativo , Proteínas de Ligação a DNA/genética , Ruminantes/genética , Análise de Sequência de DNA/métodos , Animais , Búfalos , Bovinos , Proteínas de Ligação a DNA/metabolismo , Éxons , Cabras , Masculino , Filogenia , Ruminantes/metabolismo , Ovinos , Testículo/metabolismoRESUMO
In the current study, we studied the role of signal transduction in aluminum (Al(3+))-induced DNA damage and adaptive response in root cells of Allium cepa L. The root cells in planta were treated with Al(3+) (800 µM) for 3 h without or with 2 h pre-treatment of inhibitors of mitogen-activated protein kinase (MAPK), and protein phosphatase. Also, root cells in planta were conditioned with Al(3+) (10 µM) for 2 h and then subjected to genotoxic challenge of ethyl methane sulfonate (EMS; 5 mM) for 3 h without or with the pre-treatment of the aforementioned inhibitors as well as the inhibitors of translation, transcription, DNA replication and repair. At the end of treatments, roots cells were assayed for cell death and/or DNA damage. The results revealed that Al(3+) (800 µM)-induced significant DNA damage and cell death. On the other hand, conditioning with low dose of Al(3+) induced adaptive response conferring protection of root cells from genotoxic stress caused by EMS-challenge. Pre-treatment of roots cells with the chosen inhibitors prior to Al(3+)-conditioning prevented or reduced the adaptive response to EMS genotoxicity. The results of this study suggested the involvement of MAPK and DNA repair network underlying Al-induced DNA damage and adaptive response to genotoxic stress in root cells of A. cepa.
RESUMO
Calcium is an important second messenger in signal transduction pathways. The role of Ca(2+) signalling in Al-induced DNA damage, cell death, and adaptive response to genotoxic stress caused by ethyl methanesulfonate (EMS) or methylmercuric chloride (MMCl) in the root cells of Allium cepa was investigated in the current study. Root cells in planta were treated with Al(3+) (800µM of AlCl(3)) for 3h without or with 2h pre-treatment with the Ca(2+) chelator (EGTA) or Ca(2+) channel blockers (lanthanum chloride, verapamil) or CaM/CDPK antagonist (W7). In addition, root cells in planta were conditioned by treatment with Al(3+) (5 or 10µM of AlCl(3)) for 2h followed by the genotoxic challenge with MMCl (1.25µM) or EMS (2.5 or 5mM) for 3h without or with the pre-treatment of the chosen Ca(2+) chelator/channel blockers/antagonist. Following the treatments, cell death and DNA damage were investigated in the root cells by comet assay. Furthermore, genotoxicity in the root meristems was determined after 18-30h of recovery. These results revealed that Al(3+) (800µM) significantly induced DNA damage and cell death in the root cells of A. cepa. On the other hand, conditioning of the root cells with Al(3+) at low concentrations (5 or 10µM) offered adaptive response leading to the protection against genotoxic stress induced by MMCl and EMS. Pre-treatment of root cells with the Ca(2+) chelator/channel blockers/antagonist not only alleviated Al(3+)-induced DNA damage and cell death induced but also blocked the Al(3+)-mediated adaptive response to genotoxic stress induced by MMCl and EMS. For the first time, the results of the present study highlighted the role of Ca(2+) signalling underlying the biphasic mode of action of Al(3+) that induced DNA damage and cell death at high doses and offered adaptation to genotoxic response in plants at low doses.
Assuntos
Adaptação Fisiológica , Alumínio/toxicidade , Bloqueadores dos Canais de Cálcio/farmacologia , Dano ao DNA/efeitos dos fármacos , Raízes de Plantas/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Ensaio Cometa , Metanossulfonato de Etila/toxicidade , Compostos de Metilmercúrio/toxicidade , CebolasRESUMO
Hydroponic experiments were performed with Talinum triangulare (Jacq.) Willd. focusing the root cellular biochemistry with special emphasis on DNA damage, structural, and elemental analyses in Pb(NO3)2 exposed with 0, 0.25, 0.5, 0.75, 1.0, and 1.25 mM for 7 days. Lead (Pb) increased reactive oxygen species production, lipid peroxidation, protein oxidation, cell death, and DNA damage and decreased the protein content in a dose-dependent manner. Likewise, a dose-dependent induction of antioxidative enzymes superoxide dismutase and catalase by Pb was evident. Ascorbate peroxidase on the other hand responded biphasically to Pb treatments by showing induction at low (0.25 and 0.50) and repression at high (0.75-1.25 mM) concentrations. The estimation of proline content also indicated a similar biphasic trend. Scanning electron microscope and energy-dispersive X-ray spectroscopy analysis showed that 1.25 mM Pb treatment resulted in ultrastructural modifications in roots and stem tissue that was marked by the change in the elemental profile. The findings pointed to the role of oxidative stress in the underlying Pb phytotoxicity and genotoxicity in T. triangulare.
Assuntos
Antioxidantes/metabolismo , Dano ao DNA , Gleiquênias/efeitos dos fármacos , Chumbo/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Raízes de Plantas/efeitos dos fármacos , Ascorbato Peroxidases/metabolismo , Catalase/metabolismo , Ensaio Cometa , Gleiquênias/citologia , Peróxido de Hidrogênio/metabolismo , Hidroponia/métodos , Peroxidação de Lipídeos/efeitos dos fármacos , Lipoxigenase/metabolismo , Oxirredução , Raízes de Plantas/citologia , Caules de Planta/citologia , Caules de Planta/efeitos dos fármacos , Prolina/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Superóxido Dismutase/metabolismoRESUMO
Plants under stress incur an oxidative burst that involves a rapid and transient overproduction of reactive oxygen species (ROS: O(2) (â¢-) , H(2) O(2) , (â¢) OH). We hypothesized that aluminum (Al), an established soil pollutant that causes plant stress, would induce an oxidative burst through the activation of cell wall-NADH peroxidase (NADH-PX) and/or plasma membrane-associated NADPH oxidase (NADPH-OX), leading to DNA damage in the root cells of Allium cepa L. Growing roots of A. cepa were treated with Al(3+) (800 µM of AlCl(3) ) for 3 or 6 hr without or with the pretreatment of inhibitors specific to NADH-PX and NADPH-OX for 2 hr. At the end of the treatment, the extent of ROS generation, cell death, and DNA damage were determined. The cell wall-bound protein (CWP) fractions extracted from the untreated control and the Al-treated roots under the aforementioned experimental conditions were also subjected to in vitro studies, which measured the extent of activation of peroxidase/oxidase, generation of (â¢) OH, and DNA damage. Overall, the present study demonstrates that the cell wall-bound NADH-PX contributes to the Al-induced oxidative burst through the generation of ROS that lead to cell death and DNA damage in the root cells of A. cepa. Furthermore, the in vitro studies revealed that the CWP fraction by itself caused DNA damage in the presence of NADH, supporting a role for NADH-PX in the stress response. Altogether, this study underscores the crucial function of the cell wall-bound NADH-PX in the oxidative burst-mediated cell death and DNA damage in plants under Al stress.
Assuntos
Alumínio/toxicidade , Dano ao DNA/efeitos dos fármacos , Cebolas , Peroxidases/metabolismo , Raízes de Plantas/efeitos dos fármacos , Explosão Respiratória/efeitos dos fármacos , Poluentes do Solo/toxicidade , Análise de Variância , Morte Celular/efeitos dos fármacos , Parede Celular/enzimologia , Ensaio Cometa , Eletroforese em Gel de Poliacrilamida , Raízes de Plantas/citologia , Raízes de Plantas/enzimologia , Espécies Reativas de Oxigênio/metabolismoRESUMO
Cellular responses to Al-stress in Hordeum vulgare seedling bioassay were evaluated with an objective to identify the possible biomarkers in leaf tissue that would be best suited to biomonitor aluminum (Al) in the environment. Germinating seeds were treated with different concentrations of AlCl(3) at pH 4.5 for 12h. Al-uptake and accumulation in root and leaf, generation of reactive oxygen species (ROS: O(2)(-), H(2)O(2) and ()OH), cell death, activity of antioxidant enzymes: catalase, superoxide dismutase, guaiacol peroxidase, ascorbate peroxidase, lipid peroxidation, protein oxidation, DNase activity and DNA damage were measured in leaf tissue of the seedlings on day 6 after treatment. The above parameters assessed in leaf tissue that followed a dose-response exhibited significant correlation with concentration of Al(3+) in experimental solution as well as in root tissue. The findings underscored the sensitivity as well as potential of Hordeum vulgare seedling bioassay for biomonitoring of Al in the ambient environment.
Assuntos
Alumínio/toxicidade , Hordeum/metabolismo , Folhas de Planta/metabolismo , Poluentes do Solo/toxicidade , Alumínio/metabolismo , Ascorbato Peroxidases/metabolismo , Biomarcadores/metabolismo , Catalase/metabolismo , Morte Celular , Hordeum/efeitos dos fármacos , Peroxidação de Lipídeos/efeitos dos fármacos , Oxirredução , Estresse Oxidativo , Peroxidase/metabolismo , Folhas de Planta/efeitos dos fármacos , Raízes de Plantas/efeitos dos fármacos , Raízes de Plantas/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Plântula/efeitos dos fármacos , Plântula/metabolismo , Poluentes do Solo/metabolismo , Superóxido Dismutase/metabolismoRESUMO
Silver nanoparticles (AgNP-P) from AgNO(3) were synthesized by using the broth prepared from the aromatic spath of male inflorescence of screw pine, Pandanus odorifer (Forssk.) Kuntze AgNP-P was then characterized by UV-visible spectroscopy, transmission electron microscopy (TEM) and energy-dispersive X-ray spectroscopy (EDS). Functional groups in the broth were analyzed by Fourier Transform infrared spectroscopy (FTIR). Genotoxicity of AgNP-P was assessed by utilizing our well-established Allium cepa assay system with biomarkers including the generation reactive oxygen species (ROS: O(2)(·-) and H(2)O(2)), cell death, mitotic index, micronucleus, mitotic aberrations; and DNA damage by Comet assay. Other chemical forms of silver such as Ag(+) ion, colloidal AgCl, and AgNP-S at doses 0-80 mg L(-1) were included for comparison with AgNP-P. The results revealed that AgNP-P and AgNP-S exhibited similar biological effects in causing lesser extent of cytotoxicity and greater extent of genotoxicity than that was exhibited by Ag(+) ion alone. Among different tested chemical forms of silver, colloidal AgCl was identified to be the least cytotoxic and genotoxic. Cell death and DNA-damage induced by AgNP-P were prevented by Tiron and dimethyl thiourea that scavenge O(2)(·-) and H(2)O(2), respectively. The present findings demonstrated the role of ROS in the AgNP-induced cell death and DNA damage.
Assuntos
Allium/efeitos dos fármacos , Dano ao DNA/efeitos dos fármacos , Nanopartículas Metálicas/análise , Pandanaceae/efeitos dos fármacos , Prata/análise , Testes de Toxicidade/métodos , Sal Dissódico do Ácido 1,2-Di-Hidroxibenzeno-3,5 Dissulfônico/farmacologia , Biomarcadores/análise , Morte Celular/efeitos dos fármacos , Ensaio Cometa , Peróxido de Hidrogênio/análise , Nanopartículas Metálicas/toxicidade , Testes para Micronúcleos , Microscopia Eletrônica de Transmissão , Estresse Oxidativo/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Prata/toxicidade , Compostos de Prata/análise , Compostos de Prata/toxicidade , Nitrato de Prata/análise , Nitrato de Prata/toxicidade , Espectrometria por Raios X , Tioureia/análogos & derivados , Tioureia/farmacologiaRESUMO
Experiments employing growing root cells of Allium cepa were conducted with a view to elucidate the role of reactive oxygen intermediates (ROI) in aluminium (Al)-induced DNA damage, cell death and adaptive response to genotoxic challenge imposed by ethyl methanesulphonate (EMS) or methyl mercuric chloride (MMCl). In a first set of experiments, root cells in planta were treated with Al at high concentrations (200-800 microM) for 3 h without or with pre-treatments of dihydroxybenzene disulphonic acid (Tiron) and dimethylthiourea (DMTU) for 2 h that trap O(2)(.-)and hydrogen peroxide (H(2)O(2)), respectively. At the end of treatments, generation of O(2)(.-) and H(2)O(2), cell death and DNA damage were determined. In a second set of experiments, root cells in planta were conditioned by Al at low concentrations (5 or 10 microM) for 2 h and after a 2 h intertreatment interval challenged by MMCl or EMS for 3 h without or with a pre-treatment of Tiron or DMTU. Conditioning treatments, in addition, included two oxidative agents viz rose bengal and H(2)O(2) for comparison. Following treatments, root cells in planta were allowed to recover in tap water. Genotoxicity and DNA damage were evaluated by micronucleus (MN), chromosome aberration (CA) or spindle aberration (SA) and comet assays at different hours (0-30 h) of recovery. The results demonstrated that whereas Al at high concentrations induced DNA damage and cell death, in low concentrations induced adaptive response conferring genomic protection from genotoxic challenge imposed by MMCl, EMS and Al. Pre-treatments of Tiron and DMTU prevented Al-induced DNA damage, cell death, as well as genotoxic adaptation to MMCl and EMS, significantly. The findings underscored the biphasic (hormetic) mode of action of Al that at high doses induced DNA damage and at low non-toxic doses conferred genomic protection, both of which were mediated through ROI but perhaps involving different networks.
Assuntos
Compostos de Alumínio/toxicidade , Adstringentes/toxicidade , Cloretos/toxicidade , Dano ao DNA/efeitos dos fármacos , Metanossulfonato de Etila/toxicidade , Compostos de Metilmercúrio/toxicidade , Cebolas/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Sal Dissódico do Ácido 1,2-Di-Hidroxibenzeno-3,5 Dissulfônico/farmacologia , Cloreto de Alumínio , Morte Celular/efeitos dos fármacos , Aberrações Cromossômicas , Ensaio Cometa , Sequestradores de Radicais Livres/farmacologia , Peróxido de Hidrogênio/metabolismo , Indicadores e Reagentes/farmacologia , Mutagênicos/toxicidade , Cebolas/crescimento & desenvolvimento , Estresse Oxidativo/efeitos dos fármacos , Raízes de Plantas/efeitos dos fármacos , Raízes de Plantas/crescimento & desenvolvimento , Superóxidos/metabolismo , Tioureia/análogos & derivados , Tioureia/farmacologiaRESUMO
Plant cells are constantly exposed to environmental agents and endogenous processes that inflict damage to DNA and cause genotoxic stress, which can reduce plant genome stability, growth and productivity. Plants are most affected by solar UV-B radiation, which damage the DNA by inducing the formation of two main UV photoproducts such as cyclobutane pyrimidine dimers (CPDs) and pyrimidine (6-4) pyrimidone photoproducts (6-4PPs). Reactive oxygen species (ROS) are also generated extra- or intra-cellularly, which constitute yet another source of genotoxic stress. As a result of this stress, the cellular DNA-damage responses (DDR) are activated, which transiently arrest the cell cycle and allow cells to repair DNA before proceeding into mitosis. DDR requires the activation of Ataxia telangiectasia-mutated (ATM) and Rad3-related (ATR) genes, which regulate the cell cycle and transmit the damage signals to downstream effectors of cell-cycle progression. Since genomic protection and stability are fundamental to ensure and sustain plant diversity and productivity, therefore, repair of DNA damages is essential. In plants the bulky DNA lesions, CPDs and 6-4PPs, are repaired by a simple and error-free mechanism: photoreactivation, which is a light-dependent mechanism and requires CPD or 6-4PP specific photolyases. In addition to this direct repair process, the plants also have sophisticated light-independent general repair mechanisms, such as the nucleotide excision repair (NER) and base excision repair (BER). The completed plant genome sequences reveal that most of the genes involved in NER and BER are present in higher plants, which suggests that the network of in-built DNA-damage repair mechanisms is conserved. This article describes the insight underlying the DNA damage and repair pathways in plants. The comet assay to measure the DNA damage and the role of DNA repair helicases such as XPD and XPB are also covered.
Assuntos
Dano ao DNA , DNA Helicases/metabolismo , Reparo do DNA , Plantas/enzimologia , Plantas/genética , DNA Helicases/química , Subunidades Proteicas/metabolismo , Fator de Transcrição TFIIH/metabolismoRESUMO
Aluminium (Al) was evaluated for induction of oxidative stress and DNA damage employing the growing roots of Allium cepa L. as the assay system. Intact roots of A. cepa were treated with different concentrations, 0, 1, 10, 50, 100, or 200 microM of aluminium chloride, at pH 4.5 for 4 h (or 2 h for comet assay) at room temperature, 25+/-1 degrees C. Following treatment the parameters investigated in root tissue were Al-uptake, cell death, extra cellular generation of reactive oxygen intermediates (ROI), viz. O(2)(*-), H(2)O(2) and (*)OH, lipid peroxidation, protein oxidation, activities of antioxidant enzymes namely catalase (CAT), superoxide dismutase (SOD), guaiacol peroxidase (GPX), ascorbate peroxidase (APX); and DNA damage, assessed by comet assay. The findings indicated that Al triggered generation of extra-cellular ROI following a dose-response. Through application of specific enzyme inhibitors it was demonstrated that extra-cellular generation of ROI was primarily due to the activity of cell wall bound NADH-PX. Generation of ROI in root tissue as well as cell death was better correlated to the levels of root Al-uptake rather than to the concentrations of Al in ambient experimental solutions. Induction of lipid peroxidation and protein oxidation by Al were statistically significant. Whereas Al inhibited CAT activity, enhanced SOD, GPX and APX activities significantly; that followed dose-response. Comet assay provided evidence that Al induced DNA damage in a range of concentrations 50-200 microM, which was comparable to that induced by ethylmethane sulfonate (EMS), an alkylating mutagen served as the positive control. The findings provided evidence that Al comparable to biotic stress induced oxidative burst at the cell surface through up- or down-regulation of some of the key enzymes of oxidative metabolism ultimately resulting in oxidative stress leading to DNA damage and cell death in root cells of A. cepa.
Assuntos
Alumínio/toxicidade , Dano ao DNA , Cebolas/efeitos dos fármacos , Estresse Oxidativo , Poluentes do Solo/toxicidade , Alumínio/metabolismo , Antioxidantes/metabolismo , Ascorbato Peroxidases , Catalase/metabolismo , Morte Celular/efeitos dos fármacos , Peroxidação de Lipídeos , Cebolas/metabolismo , Oxirredução , Peroxidase/metabolismo , Peroxidases/metabolismo , Proteínas de Plantas/metabolismo , Raízes de Plantas/efeitos dos fármacos , Raízes de Plantas/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Poluentes do Solo/metabolismo , Superóxido Dismutase/metabolismoRESUMO
Salicylic acid (SA), 0.01 mM, a signalling phytohormone, was tested for induction of adaptive response against genotoxicity of methyl mercuric chloride (MMCl), 0.013 mM; ethylmethane sulfonate (EMS), 2.5 mM, or maleic hydrazide (MH), 5 mM, in root meristem cells of Allium cepa. Induction of adaptive response to EMS by hydrogen peroxide (H2O2), 1 mM, and yet another secondary signal molecule was tested for comparison. Assessed by the incidence of mitoses with spindle and/or chromosome aberration and micronucleus, the findings provided evidence that SA-conditioning triggered adaptive response against the genotoxic-challenges of MMCl and EMS, but failed to do so against MH. H2O2, which is known to induce adaptive response to MMCl and MH, failed to induce the same against EMS in the present study. The findings pointed to the possible role of signal transduction in the SA-induced adaptive response to genotoxic stress that perhaps ruled out an involvement of H2O2.
Assuntos
Adaptação Biológica , Metanossulfonato de Etila/toxicidade , Hidrazida Maleica/toxicidade , Compostos de Metilmercúrio/toxicidade , Cebolas , Raízes de Plantas , Ácido Salicílico/metabolismo , Animais , Aberrações Cromossômicas , Metanossulfonato de Etila/farmacologia , Herbicidas/farmacologia , Herbicidas/toxicidade , Peróxido de Hidrogênio/farmacologia , Hidrazida Maleica/farmacologia , Meristema/citologia , Meristema/efeitos dos fármacos , Meristema/fisiologia , Compostos de Metilmercúrio/farmacologia , Testes para Micronúcleos , Mitose , Mutagênicos/farmacologia , Mutagênicos/toxicidade , Cebolas/anatomia & histologia , Cebolas/efeitos dos fármacos , Cebolas/genética , Cebolas/metabolismo , Oxidantes/farmacologia , Reguladores de Crescimento de Plantas/metabolismo , Raízes de Plantas/efeitos dos fármacos , Ácido Salicílico/farmacologia , Transdução de Sinais/fisiologia , Fuso Acromático/efeitos dos fármacosRESUMO
Subependymomas are benign intraventricular tumors with an indolent growth pattern, which are usually asymptomatic, and most commonly occur in the fourth and lateral ventricles. When symptomatic, subependymomas often obstruct critical portions of the cerebrospinal fluid (CSF) pathway, causing hydrocephalus, and range from 3 cm to 5 cm in size. We report a case of an unusually massive subependymoma of the lateral ventricles treated with subtotal resection, ventriculoperitoneal shunt, and post-surgical radiation. The clinical course, radiographic and pathologic characteristics of this massive intraventricular subependymoma are discussed, as well as the differential diagnosis of lateral ventricular masses and a review of the literature concerning subependymomas.
Assuntos
Neoplasias do Ventrículo Cerebral/diagnóstico , Glioma Subependimal/diagnóstico , Adulto , Humanos , MasculinoRESUMO
Induction and persistence of adaptive response by aluminium (Al), 1 or 10 microM, and paraquat (PQ), 5 or 10 microM, against genotoxicity of methyl mercuric chloride (MMCl), 1.26 microM, a standard environmental genotoxin, was investigated in root meristem cells of Allium cepa. Subsequently, three metabolic inhibitors, namely, 3-aminobezamide (3-AB, 10 or 100 microM), an inhibitor of poly(ADP-ribose) polymerase (PARP) implicated in DNA repair and/or apoptosis, cycloheximide (CH, 0.1 or 1 microM), an inhibitor of protein synthesis, and buthionine sulfoximine (BSO, 100 microM or 1mM), an inhibitor of glutathione synthesis were tested for their ability to prevent the adaptive response induced by conditioning doses of Al, 10 or 100 microM; and PQ, 5 or 100 microM, against MMCl-challenge, 1.26 or 100 microM, in root meristems of A. cepa or embryonic shoots of Hordeum vulgare, respectively. The findings demonstrated that once triggered, the Al- or PQ-adaptive response to MMCl could persist for at least 48h in root meristems of A. cepa. Furthermore, the adaptive response could effectively be prevented by 3-AB, to a lesser degree by CH, and the least by BSO, suggesting primarily the involvement of PARP and implicating DNA repair in the underlying mechanisms of adaptive response in plant cells in vivo.
Assuntos
Adaptação Fisiológica/efeitos dos fármacos , Alumínio/farmacologia , Antimutagênicos/farmacologia , Hordeum , Compostos de Metilmercúrio/toxicidade , Mutagênicos/toxicidade , Cebolas , Paraquat/farmacologia , Relação Dose-Resposta a Droga , Inibidores Enzimáticos/farmacologia , Hordeum/citologia , Hordeum/efeitos dos fármacos , Hordeum/genética , Micronúcleos com Defeito Cromossômico/efeitos dos fármacos , Testes para Micronúcleos , Mutagênese , Cebolas/citologia , Cebolas/efeitos dos fármacos , Cebolas/genética , Raízes de Plantas/citologia , Raízes de Plantas/efeitos dos fármacosRESUMO
Ascorbate is an essential antioxidant in the CNS, localized predominantly in neuronal cytosol. Slices of mammalian brain rapidly lose ascorbate, however, when incubated in ascorbate-free media; brain slices also take up water and swell. Here we investigated water gain in coronal slices of rat forebrain incubated with and without ascorbate for 1-3 h at 34 degrees C. Slices progressively gained water in ascorbate-free media, with a significant 12% water increase after 3 h at 34 degrees C, compared with the water content of slices after a 1-h recovery period at 24 degrees C, immediately following slice preparation. Inclusion of 400 micro M ascorbate in the medium led to an increase in tissue ascorbate content and prevented water gain at 34 degrees C. By contrast, water gain was not inhibited by isoascorbate or thiourea, which are antioxidants that are not accumulated in brain cells. The oxidant H2O2 enhanced water gain, whereas a cocktail of NMDA and non-NMDA receptor blockers inhibited edema formation to the same extent as ascorbate. These data demonstrate that brain edema, linked to glutamate-receptor activation, can result from intracellular oxidative stress and that this can be prevented by ascorbate.