144 resultados para INDUCED DAMAGE THRESHOLD


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beta-Glucans (BGs) are polysaccharides that are found in the cell walls of organisms such as bacteria, fungi, and some cereals. The objective of the present study was to investigate the genotoxic and antigenotoxic effects of BG extracted from the mushroom Agaricus brasiliensis (=Agaricus blazei Murrill ss. Heinemann). The mutagenic activity of BG was tested in single-cell gel electrophoresis assays with human peripheral lymphocytes. In addition, the protective effects against the cooked food mutagen 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2) and (+/-)-anti-B[a]P-7,8-dihydrodiol-9,10-epoxide (BPDE), which is the main metabolite of B[a]P, and against ROS (H2O2)-induced DNA damage, were studied. The results showed that the compound itself was devoid of mutagenic activity, and that a significant dose-dependent protective effect against damage induced by hydrogen peroxide and Trp-P-2 occurred in the dose range 20-80 mu g/ml. To investigate the prevention of Trp-P-2-induced DNA damage, a binding assay was carried out to determine whether BG inactivates the amine via direct binding. Since no such interactions were observed, it is likely that BG interacts with enzymes involved in the metabolism of the amine.

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Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

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Lycopene is a natural pigment synthesized by plants and microorganisms, and it is mainly found in tomatoes. It is an acyclic isomer of P-carotene and one of the most potent antioxidants. Several studies have demonstrated the ability of lycopene to prevent chemically induced DNA damage; however, the mechanisms involved are still not clear. In the present study, we investigated the antigenotoxic/antimutagenic effects of lycopene in Chinese Hamster Ovary Cells (CHO) treated with hydrogen peroxide, methylmethanesulphonate (MMS), or 4-nitroquinoline-1-oxide (4-NQO). Lycopene (97%), at final concentrations of 10, 25, and 50 M, was tested under three different protocols: before, simultaneously, and after the treatment with the mutagens. Comet and cytokinesis-block micronucleus assays were used to evaluate the level of DNA damage. Data showed that lycopene reduced the frequency of micronucleated cells induced by the three mutagens. However, this chemopreventive activity was dependent on the concentrations and treatment schedules used. Similar results were observed in the comet assay, although some enhancements of primary DNA damage were detected when the carotenoid was administered after the mutagens. In conclusion, our findings confirmed the chemopreventive activity of lycopene, and showed that this effect occurs under different mechanisms. (c) 2007 Elsevier Ltd. All rights reserved.

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Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

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The development of strategies for the protection of oral tissues against the adverse effects of resin monomers is primarily based on the elucidation of underlying molecular mechanisms. The generation of reactive oxygen species beyond the capacity of a balanced redox regulation in cells is probably a cause of cell damage. This study was designed to investigate oxidative DNA damage, the activation of ATM, a reporter of DNA damage, and redox-sensitive signal transduction through mitogen-activated protein kinases (MAPKs) by the monomer triethylene glycol dimethacrylate (TEGDMA). TEGDMA concentrations as high as 3-5 mm decreased THP-1 cell viability after a 24 h and 48 h exposure, and levels of 8-oxoguanine (8-oxoG) increased about 3- to 5-fold. The cells were partially protected from toxicity in the presence of N-acetylcysteine (NAC). TEGDMA also induced a delay in the cell cycle. The number of THP-1 cells increased about 2-fold in G1 phase and 5-fold in G2 phase in cultures treated with 3-5 mm TEGDMA. ATM was activated in THP-1 cells by TEGDMA. Likewise, the amounts of phospho-p38 were increased about 3-fold by 3 mm TEGDMA compared to untreated controls after a 24 h and 48 h exposure period, and phospho-ERK1/2 was induced in a very similar way. The activation of both MAPKs was inhibited by NAC. Our findings suggest that the activation of various signal transduction pathways is related to oxidative stress caused by a resin monomer. Signaling through ATM indicates oxidative DNA damage and the activation of MAPK pathways indicates oxidative stress-induced regulation of cell survival and apoptosis. (C) 2008 Elsevier Ltd. All rights reserved.

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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

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In this study, we show that safranine at the concentrations usually employed as a probe of mitochondrial membrane potential significantly protects against the oxidative damage of mitochondria induced by Fe(II)citrate. The effect of safranine was illustrated by experiments showing that this dye strongly inhibits both production of thiobarbituric acid-reactive substances and membrane potential decrease when energized mitochondria were exposed to Fe(II)citrate in the presence of Ca 2+ ions. Similar results were obtained with the lipophylic compound trifluoperazine. It is proposed that, like trifluoperazine, safranine decreases the rate of lipid peroxidation due to its insertion in the membrane altering the physical state of the lipid phase.

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5-azacytidine (5-azaC) treatment combined with cytosine arabinoside (ara-C) or caffeine were performed in vitro in Chinese hamster cells, CHO-K1 (wild-type) and xrs-5 (mutant) cell lines, in order to compare the cell response to the induction of chromosomal aberrations. Exponentially growing cells were treated with 5-azaC (4-16 uM) for 1 h, the cells were washed and incubated for 7 h, and 500 uM caffeine or 5 uM ara-C were added to the cultures for the last 2 h. In both cell lines, 5-azaC induced a significantly increase (P<0.01) in the frequencies of aberrations; in the combined treatments (5-azaC + Ara-C), a significant reduction (P<0.05) was observed for the aberrations which were randomly distributed. Caffeine had no influence at the same conditions. 5-azaC induced-DNA lesions were probably processed at S/G2 phase in a common pathway in both cell lines, but alternatively, 5-azaC may cause xrs-5 cells to revert to the wild-type.

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Aqueous extracts of the sporophores of eight mushroom species were assessed for their ability to prevent H2O2-induced oxidative damage to cellular DNA using the single-cell gel electrophoresis (Comet) assay. The highest genoprotective effects were obtained with cold (20°C) and hot (100°C) water extracts of Agaricus bisporus and Ganoderma lucidum fruit bodies, respectively. No protective effects were observed with Mushroom Derived Preparations (MDPs) from Flammulina velutipes, Auricularia auricula, Hypsizygus marmoreus, Lentinula edodes, Pleurotus sajor-caju, and Volvariella volvacea. These findings indicate that some edible mushrooms represent a valuable source of biologically active compounds with potential for protecting cellular DNA from oxidative damage. © 2002 Wiley-Liss, Inc.

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Purpose: To identify the electromyographic fatigue threshold in the erector spinae muscle. Methods: Eight 19 to 24-year-old male volunteers participated in this study, in which surface electrodes were used, as well as a biological signals acquisition module (Lynx) with a sampling frequency of 1000Hz, a 1000 times gain, a 20Hz high pass filter and a 500Hz low pass filter. The test consisted of repeated isometric contractions of the erector spinae muscle in a 45° hip flexion posture, with 30%, 40%, 50% and 60% of the maximum voluntary isometric contraction. Results: A positive correlation of the RMS (root mean square) value as a function of time was found for most of the subjects with 40% (N = 6), 50% (N = 7) and 60% (N = 8) loads of the maximum voluntary isometric contraction. Conclusions: It was concluded, from this study, that the proposed protocol provides evidence, through the electromyographic signal, of the development of fatigue in the erector spinae muscle with loads of 40%, 50% and 60% of the maximum voluntary isometric contraction. The protocol also allows the electromyographic fatigue threshold and its probable applicability in the diagnosis of this phenomenon during repetitive activities to be determined.

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The effects of crude extracts of the mushroom Agaricus blazei Murrill (Agaricaceae) on both DNA damage and placental form glutathione S-transferase (GST-P)-positive liver foci induced by diethylnitrosamine (DEN) were investigated. Six groups of adult male Wistar rats were used. For two weeks, animals of groups 3 to 6 were treated with three aqueous solutions of A. blazei (mean dry weight of solids being 1.2, 5.6, 11.5 and 11.5 mg/ml, respectively). After this period, groups 2 to 5 were given a single ip injection 200 mg/kg DEN and groups 1 and 6 were treated with 0.9% NaCl. All animals were subjected to 70% partial hepatectomy at week five and sacrificed 4, 24 and 48 h or 8 weeks after DEN or 0.9% NaCl treatments (10th week after the beginning of the experiment). The alkaline comet assay and GST-P-positive liver foci development were used to evaluate the influence of the mushroom extracts on liver cell DNA damage and on the initiation of liver carcinogenesis, respectively. Previous treatment with the highest concentration of A. blazei (11.5 mg/ml) significantly reduced DNA damage, indicating a protective effect against DEN-induced liver cytotoxicity/genotoxicity. However, the same dose of mushroom extract significantly increased the number of GST-P-positive liver foci.

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Dental bleaching is a simple and conservative procedure for aesthetic restoration of vital and non-vital discolored teeth. Nevertheless, a number of studies have demonstrated the risk of tissue damage from the contact of these agents with the oral mucosa. In the current study, the genotoxic potential associated with exposure to dental bleaching agents was assessed by the single cell gel (comet) assay in vitro. Chinese hamster ovary (CHO) cells in vitro were exposed to six commercial dental bleaching agents (Clarigel Gold - Dentsply; Whitespeed - Discus Dental; Nite White - Discus Dental; Magic Bleaching - Vigodent; Whiteness HP - FGM and Lase Peroxide - DMC). The results pointed out that all dental bleaching agents tested contributed to DNA damage as depicted by the mean tail moment, being the strongest effect observed with the highest dose of hydrogen peroxide (Whiteness HP and Lase peroxide, at a 35% concentration). On the other hand, Magic Bleaching (Vigodent) induced the lowest level of DNA breakage. Negative and positive controls displayed absence and presence of DNA-damaging, respectively. Taken together, these results suggest that dental bleaching agents may be a factor that increases the level of DNA damage. A higher concentration of hydrogen peroxide produced higher noxious activities in the genome as detected by single cell gel (comet) assay.