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1.
Toxicol Res (Camb) ; 13(4): tfae133, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39184218

RESUMEN

Background: Moringa oleifera and Tinospora cordifolia is extensively used as an ingredient of food and in traditional medicine for the management of a variety of diseases. Material and methods: The extracts of leaf of Moringa oleifera and stem of Tinospora cordifolia were assessed to examine their ability to inhibit the oxidative DNA damage (by DNA protection assay), cytoprotective and genoprotective potential (by Comet assay) in V79 cells individually and in combinations. Result: It was found that these extracts could significantly inhibit the OH-dependent damage of pUC18 plasmid DNA. M. oleifera extract (160 and 320 µg/mL) and Tinospora cordifolia extract (640, 1,280 and 2,560 µg/mL) individually showed higher DNA protection activity. M. oleifera (1,280 µg/mL) combined with Tinospora cordifolia (640 µg/mL) showed best cytoprotective and genoprotective activities among different concentration combinations and various concentrations of individual plants in V79 cell line against hydrogen peroxide induced cytotoxicity and genotoxicity. Conclusion: This study demonstrates the cytoprotective and genoprotective activity of M. oleifera and Tinospora cordifolia individually or in combination.

2.
Int J Mol Sci ; 24(2)2023 Jan 06.
Artículo en Inglés | MEDLINE | ID: mdl-36674623

RESUMEN

Literature data on the administration of conventional high-dose beams with (FF) or without flattening filters (FFF) show conflicting results on biological effects at the cellular level. To contribute to this field, we irradiated V79 Chinese hamster lung fibroblasts and two patient-derived glioblastoma stem-like cell lines (GSCs-named #1 and #83) using a clinical 10 MV accelerator with FF (at 4 Gy/min) and FFF (at two dose rates 4 and 24 Gy/min). Cell killing and DNA damage induction, determined using the γ-H2AX assay, and gene expression were studied. No significant differences in the early survival of V79 cells were observed as a function of dose rates and FF or FFF beams, while a trend of reduction in late survival was observed at the highest dose rate with the FFF beam. GSCs showed similar survival levels as a function of dose rates, both delivered in the FFF regimen. The amount of DNA damage measured for both dose rates after 2 h was much higher in line #1 than in line #83, with statistically significant differences between the two dose rates only in line #83. The gene expression analysis of the two GSC lines indicates gene signatures mimicking the prognosis of glioblastoma (GBM) patients derived from a public database. Overall, the results support the current use of FFF and highlight the possibility of identifying patients with candidate gene signatures that could benefit from irradiation with FFF beams at a high dose rate.


Asunto(s)
Glioblastoma , Humanos , Glioblastoma/genética , Glioblastoma/radioterapia , Planificación de la Radioterapia Asistida por Computador/métodos , Pulmón , Dosificación Radioterapéutica
3.
Bull Exp Biol Med ; 172(5): 558-560, 2022 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-35348959

RESUMEN

The development of technologies for using the Novac-11 pulsed electron accelerator in radiation therapy of animals with spontaneous neoplasms requires dosimetric and radiobiological studies. The studies were performed on cultured Chinese hamster V-79 fibroblasts after irradiation with 10 MeV electrons in a dose range up to 12 Gy and 60Co γ-radiation. Chemical dosimeters FBX and Fricke were used as additional test-systems. The depth dose curves were measured and the maximum dose depth of the electron beam was determined in tissue-equivalent phantoms. Cell survival and the data of chemical dosimetric systems showed that the effects of electron irradiation did not differ from that of 60Co γ-radiation. It was concluded that the use of Novac-11 in the therapy of animals with spontaneous neoplasms is advisable.


Asunto(s)
Electrones , Radiometría , Animales , Rayos gamma , Mamíferos , Fantasmas de Imagen
4.
Chemosphere ; 291(Pt 1): 132784, 2022 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-34742755

RESUMEN

Polybrominated biphenyl ethers (PBDEs) are a group of persistent organic pollutants with endocrine-disrupting, neurotoxic, tumorigenic and DNA-damaging activities. They are hydroxylated by human liver microsomal CYP enzymes, however, their mutagenicity remains unknown. In this study, 2,2',4,4'-tetrabromobiphenyl ether (BDE-47, relatively abundant in human tissues) was investigated for micronuclei induction and DNA damage in mammalian cells. The results indicated that BDE-47 up to 80 µM under a 6 h/18 h (exposure/recovery, covering 2 cell cycles) regime did not induce micronuclei in V79-Mz and V79-derived cell lines expressing human CYP1A1 or 1A2, while it was moderately positive in human CYP2B6-, 2E1-and 3A4-expressing cell lines (V79-hCYP2B6, V79-hCYP2E1-hSULT1A1 and V79-hCYP3A4-hOR, respectively). Following 24 h exposure, BDE-47 induced micronuclei in V79-hCYP2E1-hSULT1A1 and V79-hCYP3A4 cells at increased potencies. In the human hepatoma (HepG2) cells BDE-47 (48 h exposure) was inactive up to 40 µM, however, pretreatment of the cells with ethanol (0.2%, v:v, inducer of CYP2E1) or rifampicin (10 µM, inducer of CYP3A4) led to significant micronuclei formation by BDE-47; pretreatment with bisphenol AF (100 nM) also potentiated BDE-47-induced micronuclei formation (which was blocked by a CYP2E1 inhibitor trans-1,2-dichloroethylene or a CYP3A inhibitor (ketoconazole). Immunofluorescent staining of centromere protein B with the micronuclei formed by BDE-47 in HepG2 cells pretreated with ethanol or rifampicin demonstrated selective formation of centromere-containing micronuclei. The increased phosphorylation of both histones H2AX and H3 in HepG2 by BDE-47 also indicated an aneugenic potential. Therefore, this study suggests that BDE-47 is an aneugen activated by several human CYP enzymes.


Asunto(s)
Éter , Éteres Difenilos Halogenados , Animales , Cricetinae , Cricetulus , Daño del ADN , Éteres Difenilos Halogenados/toxicidad , Humanos
5.
Radiat Environ Biophys ; 61(1): 49-57, 2022 03.
Artículo en Inglés | MEDLINE | ID: mdl-34751828

RESUMEN

The study of depriving cells from background ionizing radiation for the past decades has provided valuable insights into its role in cellular homeostasis control. To explore the existence of such response in eukaryotic cells, we grew Chinese hamster (Cricetulus griseus) V79 cells for 23 days using three different dose rates: 0.91 (below background), 35 (surface control) and 72 nGy h-1 (underground KCl-amended control). We did not observe a significant difference in cell number during the course of the experiment. However, cells grown at below background showed significantly lower viability compared to those grown at both control levels after 5 days of incubation and lasted, intermittently, for up to 21 days. We also observed a clear differentiation between the underground and the surface controls that could be explained by the variety of radiation sources present during cell growth under unshielded conditions. To explore the molecular mechanisms for these responses we performed transcriptome analysis on samples collected on days 2 and 5, but only samples from day 5 resulted in significant regulation. Gene enrichment analysis revealed two control-dependent general transcriptional responses. When compared the underground-KCl control, below-background cells showed the upregulation of processes intended for the response to drugs, metals and mechanical stimuli. In comparison, the response relative to the surface control was characterized by the upregulation of responses to organic substances and abiotic stimuli involved in the regulation of signaling, as well as to cell proliferation and homeostatic control of the number of cell processes.


Asunto(s)
Radiación de Fondo , Perfilación de la Expresión Génica , Animales , Línea Celular , Proliferación Celular , Cricetinae , Cricetulus
6.
Front Genet ; 12: 698046, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34603371

RESUMEN

Background: Prior studies have shown that the proliferation of V79 lung fibroblast cells could be inhibited by low background radiation (LBR) in deep underground laboratory (DUGL). In the current study, we revealed further molecular changes by performing whole transcriptome analysis on the expression profiles of long non-coding RNA (lncRNA), messenger RNA (mRNA), circular RNA (circRNA) and microRNA (miRNA) in V79 cells cultured for two days in a DUGL. Methods: Whole transcriptome analysis including lncRNA, mRNAs, circ RNA and miRNA was performed in V79 cells cultured for two days in DUGL and above ground laboratory (AGL), respectively. The differentially expressed (DE) lncRNA, mRNA, circRNA, and miRNA in V79 cells were identified by the comparison between DUGL and AGL groups. Quantitative real-time polymerase chain reaction(qRT-PCR)was conducted to verify the selected RNA sequencings. Then, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway was analyzed for the DE mRNAs which enabled to predict target genes of lncRNA and host genes of circRNA. Results: With |log2(Fold-change)| ≥ 1.0 and p < 0.05, a total of 1257 mRNAs (353 mRNAs up-regulated, 904 mRNAs down-regulated), 866 lncRNAs (145 lncRNAs up-regulated, 721 lncRNAs down-regulated), and 474 circRNAs (247 circRNAs up-regulated, 227 circRNAs down-regulated) were significantly altered between the two groups. There was no significant difference in miRNA between the two groups. The altered RNA profiles were mainly discovered in lncRNAs, mRNAs and circRNAs. DE RNAs were involved in many pathways including ECM-RI, PI3K-Akt signaling, RNA transport and the cell cycle under the LBR stress of the deep underground environment. Conclusion: Taken together, these results suggest that the LBR in the DUGL could induce transcriptional repression, thus reducing metabolic process and reprogramming the overall gene expression profile in V79 cells.

7.
Artículo en Inglés | MEDLINE | ID: mdl-33985697

RESUMEN

Coal burning generates gases, particles, and condensation by-products that are harmful to soil, water, and to the atmosphere. The aim of this study was to characterize and identify the cytotoxic and mutagenic potential of soil samples from the cities of Aceguá, Bagé, Candiota and Pinheiro Machado, near a large coal-fired power plant. Our study describes soil characteristics and contributes to the evaluation of the genotoxic activity of coal mining and burning, using the Comet Assay and Micronucleus test in V79 cells, as well as mutagenicity assays with Salmonella typhimurium strains. Comet Assay results show that the winter soil samples of Candiota and Pinheiro Machado induced a significant increase of the Damage Index for cells, as well as for the Aceguá summer sample. The micronucleus test did not detect differences between cities and seasons. A component analysis indicates associations between results obtained in Comet Assay and Ti and phenanthene concentrations for Pinheiro Machado during the winter, and Al for Aceguá during the summer and Zn during the winter. Results of Salmonella/microsome assays were negative, only Candiota and Pinheiro Machado samples showed a statistical increase of his + colonies in TA102. Our work describes biological data on these cells exposed to coal-contaminated soil, confirming the sensitivity of the Comet Assay in V79 cells and Salmonella/microsome assay for the evaluation of the effects of complex mixtures. These findings help to understand the spatial distribution of contaminants in the local soil related to a power plant, which is important for planning public safety actions.


Asunto(s)
Carbón Mineral/análisis , Suelo/química , Animales , Brasil , Línea Celular , Ciudades , Carbón Mineral/toxicidad , Minas de Carbón/métodos , Ensayo Cometa/métodos , Cricetulus , Daño del ADN/efectos de los fármacos , Monitoreo del Ambiente/métodos , Pruebas de Micronúcleos/métodos , Mutagénesis/efectos de los fármacos , Mutágenos/toxicidad , Centrales Eléctricas , Estaciones del Año
8.
J Toxicol Environ Health A ; 84(17): 689-701, 2021 09 02.
Artículo en Inglés | MEDLINE | ID: mdl-34034641

RESUMEN

Nicotiana tabacum is the most cultivated tobacco species in the state of Rio Grande do Sul, Brazil. Workers who handle the plant are exposed to the leaf components during the harvesting process and when separating and classifying the dried leaves. In addition to nicotine, after the drying process, other components may be found including tobacco-specific nitrosamines, polycyclic aromatic hydrocarbons, as well as pesticides residues. The objective of this study was to examine the genotoxicity attributed to the aqueous extract of dried tobacco leaves obtained from tobacco barns using Chinese hamster lung fibroblast cells (V79) as a model system by employing alkaline comet assay, micronucleus (MN) and Ames test. MTT assay was used to assess cytotoxicity and establish concentrations for this study. Data demonstrated cell viability > 85% for concentrations of 0.625-5 mg/ml while the comet assay indicated a significant increase in DNA damage at all concentrations tested. A significant elevation of MN and nuclear buds (NBUD) was found for 5 mg/ml compared to control and other dry tobacco leaves concentrations (0.625-2.5 mg/ml). Mutagenicity was not found using the Salmonella/Microsome test (TA98, TA100, and TA102 strains) with and without metabolic activation. The concentration of inorganic elements was determined employing the PIXE technique, and 13 inorganic elements were detected. Using CG/MS nicotine amounts present were 1.56 mg/g dry tobacco leaf powder. Due to the observed genotoxicity in V79 cells, more investigations are needed to protect the health of tobacco workers exposed daily to this complex mixture of toxic substances present in dry tobacco leaves.


Asunto(s)
Mutágenos/toxicidad , Nicotiana/química , Hojas de la Planta/química , Animales , Línea Celular , Ensayo Cometa , Cricetulus , Pruebas de Micronúcleos , Pruebas de Mutagenicidad
9.
J Toxicol Environ Health A ; 83(19-20): 659-671, 2020 10 17.
Artículo en Inglés | MEDLINE | ID: mdl-32865139

RESUMEN

CECROPIA PACHYSTACHYA: leaves are popularly used to treat asthma and diabetes. Despite the widespread consumption of this plant, there are few scientific studies regarding its toxicological potential. In order to conduct a thorough study concerning the potential adverse effects, the aim of this study was to assess acute and subacute toxicity tests of crude aqueous extract from C. pachystachya leaves (CAE-Cp) using in vivomodel, as well as in vitro cytotoxicity, genotoxicity and antioxidant activity. In addition, genotoxicity, and cytotoxicity of chlorogenic acid (CGA) and cytotoxicity of isoorientin (ISOO) were also evaluated. The antioxidant activity was verified by DPPH, cytotoxicity using sulforhodamine B (SRB) assay and genotoxicity by comet assay on V79 cells. The phytochemical analysis of CAE-Cp detected flavonoids and tannins, CGA and ISOO as the major compounds utilizing HPLC. The total flavonoid content (6.52 mg/g EQ) and antioxidant activity (EC50 = 62.15 µg/ml) of CAE-Cp were determined. In vitro evaluations with CAE-Cp showed genotoxic effects at 0.31 to 2.5 mg/ml and an expressive cytotoxicity on HT-29 (IC50 = 4.43 µg/ml) cells. CGA was genotoxic against V79 cells at 0.07 mg/ml and cytotoxic against to HT-29 (IC50 = 71.70 µg/ml), OVCAR-3 (IC50 = 80.07 µg/ml), MCF-7 (IC50 = 45.58 µg/ml) and, NCI-H460 (IC50 = 71.89 µg/ml) cancer cell lines. Wistar rats treated with a single dose (2,000 mg/kg) CAE-Cp decreased hemoglobin levels after 14 days, although no significant toxicity was observed in animals after 28 days. In view of the in vitro cytotoxicity and genotoxicity detected, further studies are necessary to establish the safe use of CAE-Cp.


Asunto(s)
Antioxidantes/toxicidad , Cecropia/química , Ácido Clorogénico/toxicidad , Citotoxinas/toxicidad , Luteolina/toxicidad , Mutágenos/toxicidad , Extractos Vegetales/toxicidad , Animales , Masculino , Extractos Vegetales/química , Hojas de la Planta/química , Ratas , Ratas Wistar , Pruebas de Toxicidad Aguda , Pruebas de Toxicidad Subaguda
10.
Nanomaterials (Basel) ; 10(3)2020 Mar 05.
Artículo en Inglés | MEDLINE | ID: mdl-32150818

RESUMEN

The genotoxicity of anatase/rutile TiO2 nanoparticles (TiO2 NPs, NM105 at 3, 15 and 75 µg/cm2) was assessed with the mammalian in-vitro Hypoxanthine guanine phosphoribosyl transferase (Hprt) gene mutation test in Chinese hamster lung (V79) fibroblasts after 24 h exposure. Two dispersion procedures giving different size distribution and dispersion stability were used to investigate whether the effects of TiO2 NPs depend on the state of agglomeration. TiO2 NPs were fully characterised in the previous European FP7 projects NanoTEST and NanoREG2. Uptake of TiO2 NPs was measured by transmission electron microscopy (TEM). TiO2 NPs were found in cytoplasmic vesicles, as well as close to the nucleus. The internalisation of TiO2 NPs did not depend on the state of agglomeration and dispersion used. The cytotoxicity of TiO2 NPs was measured by determining both the relative growth activity (RGA) and the plating efficiency (PE). There were no substantial effects of exposure time (24, 48 and 72 h), although a tendency to lower RGA at longer exposure was observed. No significant difference in PE values and no increases in the Hprt gene mutant frequency were found in exposed relative to unexposed cultures in spite of evidence of uptake of NPs by cells.

11.
Artículo en Inglés | MEDLINE | ID: mdl-31382475

RESUMEN

In previous investigations, we demonstrated that pre-exposure of different cell cultures to radiofrequency fields can reduce the damage induced by genotoxic agents, an effect resembling the so-called adaptive response. In this study, we pre-exposed human peripheral blood lymphocytes and Chinese hamster lung fibroblast cell line to 1950 MHz, UMTS (Universal Mobile Telecommunication System) signal, for 20 h, and then treated cultures with Mitomycin-C. After confirming the induction of an adaptive response in terms of the reduction of micronuclei formation, we observed that such a response was negated by treatments with 3-aminobenzamide. Since 3-aminobenzamide is an inhibitor of poly (ADP-ribose) polymerase enzyme, which is involved in DNA repair, these results support the possible involvement of DNA repair mechanisms in radiofrequency-induced adaptive response.


Asunto(s)
Adaptación Fisiológica/efectos de los fármacos , Benzamidas/farmacología , Modelos Biológicos , Ondas de Radio , Animales , Línea Celular , Células Cultivadas , Cricetinae , Cricetulus , Daño del ADN , Reparación del ADN , Humanos , Linfocitos/efectos de los fármacos , Micronúcleos con Defecto Cromosómico , Mitomicina/farmacología , Poli(ADP-Ribosa) Polimerasa-1/antagonistas & inhibidores
12.
J Photochem Photobiol B ; 185: 192-198, 2018 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-29957498

RESUMEN

Photosensitization of V79 Chinese hamster lung fibroblasts was tested to investigate if the cells can fit the photoactive effect of alpha-terthienyl for safety application. Using 15-min photoirradiation of a black light (320-400 nm, 40 W), alpha-terthienyl was significantly photoactivated and caused V79 cells to be shrinkage, detachment and necrosis. The photoactivated alpha-terthienyl played a concentration-dependent stress to decrease cell survival and to induce cell death with median inhibitory concentration (IC50) as 4.78 µg/ml. Cell viability in MTT assays also fell down to 10.58% of the control in the treatment of 10.0 µg/ml photoactivated alpha-terthienyl. As the irradiation time prolonged and the concentration of photoactivated alpha-terthienyl increased, cell death increased significantly, the intracellular level of reactive oxygen species (ROS) and the content of extracellular malondialdehyde were gradually increased. The changes of peroxidase, superoxide dismutase and catalase activities in V79 cells were positively responsive to the oxidative stress caused by photoactivated alpha-terthienyl. Moreover, using non-photosensitizing condition, the increased cell death and oxidative stress in the treatment of alpha-terthienyl at >7.0 µg/ml were also observed. The results showed the maladjustment response of V79 cells with membrane damage and cell death, clearly demonstrating the photosensitization of animal cells to the photoactivated cytotoxic effect of alpha-terthienyl.


Asunto(s)
Membrana Celular/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Tiofenos/farmacología , Animales , Apoptosis/efectos de los fármacos , Apoptosis/efectos de la radiación , Catalasa/metabolismo , Línea Celular , Membrana Celular/metabolismo , Membrana Celular/efectos de la radiación , Supervivencia Celular/efectos de los fármacos , Cricetinae , Cricetulus , Luz , Malondialdehído/metabolismo , Estrés Oxidativo/efectos de la radiación , Especies Reactivas de Oxígeno/metabolismo , Superóxido Dismutasa/metabolismo , Tiofenos/química
13.
Ind Health ; 55(6): 580-583, 2017 Dec 07.
Artículo en Inglés | MEDLINE | ID: mdl-29021414

RESUMEN

Health effects caused by ionizing radiations raise considerable concern among general public and radiation workers. To estimate ability of personal protective equipment (PPE) materials that reduce toxic effects of ionizing radiations, we developed an experimental bioassay system using Chinese Hamster V79 cells. The system developed here distinguished the biological effectiveness of X-ray that was significantly affected by elements composed of shielding materials. Survival of the cells exposed to sub-lethal dose of X-ray was enhanced more than 2 times when the X-ray was filtrated by a lead plate. Also filtration of the X-ray with a tungsten plate enhanced the cell survival more than three times. These results suggested the colony assay system developed here was useful for examination of the biological effectiveness of X-ray and the ability of PPE materials reducing the toxic effects caused by ionizing radiations.


Asunto(s)
Bioensayo/métodos , Supervivencia Celular/efectos de la radiación , Equipo de Protección Personal/normas , Radiación Ionizante , Animales , Línea Celular , Cricetinae , Cricetulus , Plomo , Ensayo de Materiales/métodos , Tungsteno , Rayos X
14.
Artículo en Inglés | MEDLINE | ID: mdl-28137365

RESUMEN

Botryosphaeran (BOT) is an exocellular ß-d-glucan (carbohydrate biopolymer) of the (1→3;1→6)-linked type produced by Botryosphaeria rhodina MAMB-05. The cytotoxic, mutagenic, genotoxic, and protective effects of this substance were evaluated in Chinese hamster lung fibroblasts (V79) and rat hepatocarcinoma cells (HTC) by the micronucleus test (MN) and the comet assay. BOT was not genotoxic in either cell line; it decreased the clastogenic effects of doxorubicin, H2O2, and benzo[a]pyrene. These results indicate that BOT may have potential as a therapeutic agent.


Asunto(s)
Antimutagênicos/farmacología , Glucanos/farmacología , Animales , Cricetinae , Cricetulus , Técnicas In Vitro , Pruebas de Mutagenicidad , Ratas
15.
Arch Toxicol ; 91(9): 3175-3184, 2017 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-28160022

RESUMEN

Heterocyclic aromatic amines (HAAs) are primarily produced during the heating of meat or fish. HAAs are mutagenic and carcinogenic, and their toxicity in model systems depend on metabolic activation. This activation is mediated by cytochrome P450 (CYP) enzymes, in particular CYP1A2. Some studies have indicated a role of human sulfotransferase (SULT) 1A1 and N-acetyltransferase (NAT) 2 in the terminal activation of HAAs. In this study, we conducted a metabolism/genotoxicity relationship analysis for 16 HAAs and related heterocyclics. We used the γH2AX genotoxicity assay in V79 cells (deficient in CYP, SULT and NAT) and V79-derived cell lines genetically engineered to express human CYP1A2 alone or in combination with human SULT1A1 or NAT2. Our data demonstrated genotoxic properties for 13 out of the 16 compounds tested. A clear relationship between metabolic bioactivation and genotoxicity allowed to distinguish four groups: (1) Trp-P-1 genotoxicity was linked to CYP1A2 bioactivation only-with negligible effects of phase II enzymes; (2) Glu-P-2, Glu-P-1, Trp-P-2, APNH, MeAαC and AαC were bioactivated by CYP1A2 in combination with either phase II enzyme tested (NAT2 or SULT1A1); (3) IQ, 4-MeIQ, IQx, 8-MeIQx, and 4,8-DiMeIQx required CYP1A2 in combination with NAT2 to be genotoxic, whereas SULT1A1 did not enhance their genotoxicity; (4) PhIP became genotoxic after CYP1A2 and SULT1A1 bioactivation-NAT2 had not effect. Our results corroborate some previous data regarding the genotoxic potency of seven HAAs and established the genotoxicity mechanism for five others HAAs. This study also permits to compare efficiently the genotoxic potential of these 13 HAAs.


Asunto(s)
Arilamina N-Acetiltransferasa/metabolismo , Arilsulfotransferasa/metabolismo , Compuestos Heterocíclicos/farmacocinética , Activación Metabólica , Animales , Arilamina N-Acetiltransferasa/genética , Arilsulfotransferasa/genética , Citocromo P-450 CYP1A2/genética , Citocromo P-450 CYP1A2/metabolismo , Compuestos Heterocíclicos/toxicidad , Humanos , Imidazoles/farmacocinética , Pruebas de Mutagenicidad/métodos , Mutágenos/farmacocinética , Quinoxalinas/farmacocinética , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo
16.
Bioelectromagnetics ; 38(4): 245-254, 2017 May.
Artículo en Inglés | MEDLINE | ID: mdl-28072461

RESUMEN

In this study, the effect of radiofrequency (RF) exposure to 1950 MHz, Universal Mobile Telecommunication System signal, was investigated in Chinese hamster lung fibroblast cell line (V79). Genotoxic and cytotoxic effects of 20-h exposure at specific absorption rate (SAR) values from 0.15 W/kg to 1.25 W/kg were measured by means of cytokinesis-block micronucleus (MN) assay. Exposure was carried out blinded under strictly controlled conditions of dosimetry and temperature. The effect of RF exposure alone at four SAR values was tested, that is, 0.15, 0.3, 0.6, and 1.25 W/kg. A statistically significant increase in MN frequency was found in cultures exposed to 0.15 and 0.3 W/kg (P < 0.05) compared to sham-exposed ones, in the absence of cytotoxicity. SAR values of 0.6 and 1.25 W/kg did not exert any effect. Moreover, to evaluate the ability of RF to exert protective effects with respect to a chemical mutagen, cell cultures were also pre-exposed for 20 h at 0.3 or 1.25 W/kg, and then treated with 500 ng/ml of mitomycin-C (MMC). A significant reduction in the frequency of MN was detected in cultures pre-exposed to 1.25 W/kg compared to cultures treated with MMC alone (P < 0.05), indicating induction of adaptive response. Such a decrease was not induced by pre-exposure at 0.3 W/kg SAR. Taken together, our results indicated that V79 is a sensitive cell model to evidence either adverse or beneficial effects of RF exposure, depending on experimental conditions applied. Bioelectromagnetics. 38:245-254, 2017. © 2017 Wiley Periodicals, Inc.


Asunto(s)
Fibroblastos/efectos de la radiación , Pulmón/citología , Ondas de Radio/efectos adversos , Adaptación Fisiológica/efectos de la radiación , Animales , Línea Celular , Cricetinae , Cricetulus , Citocinesis/efectos de la radiación , Daño del ADN , Fibroblastos/citología , Fibroblastos/metabolismo , Pruebas de Micronúcleos
17.
Chemosphere ; 169: 239-248, 2017 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-27880922

RESUMEN

Brewery effluents contain complex mixtures that are discharged into rivers. Therefore, it is necessary to evaluate the genotoxic potential of these effluents. The study evaluated the genotoxicity of surface water and sediment samples from the Jacuí River in the state of Rio Grande do Sul, Brazil, which received effluents discharged from a brewery. The Salmonella/microsome test, Comet Assay and Micronucleus test on V79 cells, as well as the element profile (PIXE) and PAHs levels were used for this purpose. The surface water and sediment samples were collected in summer at three sites: 1 km upstream from the brewery discharge site (Site A); in front of the effluent discharge site, after chemical and biological treatment (Site B); about 1 km downstream from the discharge site (Site C). Only a sediment sample from Site A induced a mutagenic effect using the Salmonella/microsoma test (TA97a). All three sites presented genotoxicity (A, B and C), both for water and sediments using comet assay, and mutagenicity in the samples from Site B (surface water) and Site A and Site C (sediments) using the micronuclei tests. The results of PIXE and PAHs showed higher levels of elements for samples obtained from sites upstream and downstream from the effluent discharge. Environmental samples consist of complex mixtures of chemicals, and it is difficult to associate DNA damage with a specific element. This study showed that brewery effluent contains metals and PAHs that can induce in vitro genotoxicity under the conditions of this study.


Asunto(s)
Cerveza , Monitoreo del Ambiente , Hidrocarburos Policíclicos Aromáticos/análisis , Hidrocarburos Policíclicos Aromáticos/toxicidad , Aguas Residuales/toxicidad , Contaminantes Químicos del Agua/toxicidad , Brasil , Ensayo Cometa , Daño del ADN , Monitoreo del Ambiente/métodos , Residuos Industriales , Pruebas de Micronúcleos , Mutágenos/toxicidad , Ríos , Contaminantes Químicos del Agua/análisis
18.
Artículo en Inglés | MEDLINE | ID: mdl-27476330

RESUMEN

Several studies have reported that guanylhydrazones display a variety of desirable biological properties, such as antihypertensive, antibacterial, and antimalarial behaviour. They furthermore promote anti-pneumocystosis and anti-trypanosomiasis, exhibit antitumor activity, and show significant cytotoxicity against cancer cell lines. In this work, we have evaluated the cytotoxicity, mutagenicity, and genotoxicity of two guanylhydrazones derivatives, (E)-2-[(2,3-dimethoxyphenyl) methylene] hydrazine carboxymidamide hydrochloride (2,3-DMeB) and (E)-2-[(3,4-dimethoxyphenyl) methylene] hydrazine carboxymidamide hydrochloride (3,4-DMeB), in different biological models. Both 2,3-DMeB and 3,4-DMeB induce weak cytotoxic and mutagenic effects in bacteria and yeast. The genotoxicity of these compounds was determined in a fibroblast cell line (V79) using alkaline comet assay, as well as a modified comet assay with bacterial enzymes formamidopyrimidine DNA-glycosylase (FPG) and endonuclease III (EndoIII). Both guanylhydrazone derivatives induced DNA damage. Treatment of V79 cells with EndoIII and FPG proteins demonstrated a significant effect of 2,3-DMeB and 3,4-DMeB with respect to oxidized bases. In addition, the derivatives induced a significant increase in the frequency of micronucleated cells at high doses. The antifungal and anti-trypanosomal properties of these guanylhydrazone derivatives were also evaluated, and the obtained results suggest that 2,3-DMeB is more effective than 3,4-DMeB. The biological activity of 2,3-DMeB and 3,4-DMeB may thus be related, at least in part, to their oxidative potential, as well as to their ability to interact with DNA. Considering the previously reported in vitro antitumor activity of guanylhydrazone derivatives in combination with the lack of acute toxicity and the fact that DNA damage is only observed at high doses should render both compounds good candidates for in vivo studies on antitumor activity.


Asunto(s)
Daño del ADN/efectos de los fármacos , Hidrazonas/toxicidad , Mutágenos/toxicidad , Animales , Antifúngicos/toxicidad , Línea Celular , Ensayo Cometa , Cricetulus , Humanos , Peroxidación de Lípido/efectos de los fármacos , Pruebas de Mutagenicidad , Tripanocidas/toxicidad , Trypanosoma cruzi/efectos de los fármacos
19.
Chemosphere ; 159: 610-618, 2016 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-27343868

RESUMEN

The effects of fine inhalable particles (PM2.5) were evaluated in an area under the influence of a petrochemical industry, investigating the sensitivity of different genotoxicity biomarkers. Organic extracts were obtained from PM2.5 samples at two sites, positioned in the first and second preferential wind direction in the area. The extracts were evaluated with Salmonella/microsome assay, microsuspension method, strains TA98, YG1021 and YG1024. The mammalian metabolization fraction (S9) was used to evaluate metabolite mutagenicity. The Comet Assay (CA) and Micronuclei Test were used in a Chinese hamster lung cell line (V79). All extracts showed mutagenicity in Salmonella, and nitrogenated compounds were strongly present. Genotoxicity were found in CA in almost all extracts and the micronuclei induction at the Site in the first (Autumn 1, Winter 1), and in the second (Spring 2) wind direction. V79 showed cytotoxicity in all samples. The three biomarkers were concordant in characterization Site NO with worse quality, compatible with the greater pollutants dispersion in the first wind direction. All PM2.5 concentrations were lower than those recommended by air quality standards but genotoxic effects were detected in all samples, corroborating that these standards are inadequate as quality indicators. The Salmonella/microsome assay proved sensitive to PM2.5 mutagenicity, with an outstanding influence of nitroarenes and aromatic amines. Analyses using CA and the micronucleus test broadened the levels of response that involve different damage induction mechanisms. Results show that the complex PM2.5 composition can provoke various genotoxic effects and the use of different bioassays is essential to understand its effects.


Asunto(s)
Contaminantes Atmosféricos/análisis , Mutágenos/análisis , Material Particulado/análisis , Contaminantes Atmosféricos/toxicidad , Animales , Bioensayo , Biomarcadores/análisis , Línea Celular , Ensayo Cometa , Cricetinae , Daño del ADN , Industrias , Pruebas de Micronúcleos , Pruebas de Mutagenicidad , Mutágenos/toxicidad , Material Particulado/toxicidad , Hidrocarburos Policíclicos Aromáticos/análisis , Salmonella/efectos de los fármacos , Salmonella typhimurium/efectos de los fármacos , Estaciones del Año
20.
Pharm Biol ; 54(11): 2786-2790, 2016 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-27159582

RESUMEN

CONTEXT: Solanum lycocarpum A. St.-Hil. (Solanaceae), popularly known as 'fruta-do-lobo' (wolf fruit), 'lobeira' and 'jurubebão', is commonly used by native people of Central Brazil in powder form or as a hydroalcoholic extract for the management of diabetes and obesity and to decrease cholesterol levels. OBJECTIVE: The present study determines the possible cytotoxic, genotoxic and antigenotoxic activities of hydroalcoholic extract of the S. lycocarpum fruits (SL). MATERIALS AND METHODS: The clonogenic efficiency assay was used to determine the cytotoxicity. Three concentrations of SL (16, 32 and 64 µg/mL) were used for the evaluation of its genotoxic and antigenotoxic potential on V79 cells using the micronucleus and comet assays. In the antigenotoxicity assays, the cells were treated simultaneously with SL and the alkylating agent methyl methanesulphonate (MMS, 44 µg/mL for the micronucleus assay and 22 µg/mL for the comet assay) as an inducer of micronuclei and DNA damage. RESULTS: The results showed that SL was cytotoxic at concentrations up to 64 µg/mL. No significant differences in the rate of chromosome or DNA damage were observed between cultures treated with SL and the control group. In addition, the frequencies of micronuclei and DNA damage induced by MMS were significantly reduced after treatment with SL. The damage reduction percentage ranged from 68.1% to 79.2% and 12.1% to 16.5% for micronucleus and comet assays, respectively. DISCUSSION AND CONCLUSION: SL exerted no genotoxic effect and exhibited chemopreventive activity against both genomic and chromosome damage induced by MMS.


Asunto(s)
Extractos Vegetales/farmacología , Solanum , Animales , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Cricetinae , Cricetulus , Daño del ADN , Metilmetanosulfonato/toxicidad , Pruebas de Micronúcleos , Pruebas de Mutagenicidad , Extractos Vegetales/toxicidad
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