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1.
Toxicol Lett ; 328: 1-6, 2020 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-32315709

RESUMO

The genotoxicity of cationic lipopeptide nanoparticles (cLPNPs) was evaluated in vivo and in vitro comet assay and the in vivo chromosome aberrations test. In vitro comet assay, human blood cells were exposed to cLPNPs at the concentration of 2.5, 5, 10, 20, 40 and 100 µg/mL. Significant DNA damage was observed after 1 h exposure, but no effects were detected after 3 h. In vivo, cLPNPs were administered in single or five daily injection doses at 8, 20 and 40 mg/kg of body weight by subcutaneous injection to male mice. The cLPNPs caused DNA damage in the liver, lung and kidney, but not in the spleen. The kidney was more prone to genotoxic effects that persisted from 24 h to 14d after a single injection of cLPNPs. No statistically significant increase in the percentage of cells with chromosomal aberrations above the vehicle control was observed in mice bone marrow after a single or repeated injection of cLPNPs. In summary, cLPNPs shown to be genotoxic both in vivo and in vitro. The results suggest the importance of the use of highly sensitive methods, such as the comet assay, in order to determine the full genotoxic potential of nanoparticles.


Assuntos
Aberrações Cromossômicas/induzido quimicamente , Dano ao DNA , Lipopeptídeos/toxicidade , Nanopartículas/toxicidade , Animais , Células da Medula Óssea/efeitos dos fármacos , Células da Medula Óssea/patologia , Sobrevivência Celular/efeitos dos fármacos , Ensaio Cometa , Relação Dose-Resposta a Droga , Humanos , Injeções Subcutâneas , Rim/efeitos dos fármacos , Rim/patologia , Leucócitos Mononucleares/efeitos dos fármacos , Leucócitos Mononucleares/patologia , Lipopeptídeos/química , Fígado/efeitos dos fármacos , Fígado/patologia , Pulmão/efeitos dos fármacos , Pulmão/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos CBA , Nanopartículas/química
2.
Int J Occup Environ Med ; 11(1): 33-40, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31905193

RESUMO

BACKGROUND: Workers in cement warehouses of Kerala are enduring long-standing exposure to cement dust, which is considered genotoxic. OBJECTIVE: To evaluate the extent of genotoxicity and cytotoxicity caused due to exposure of cement dust among those working in cement warehouses. METHODS: The study included 82 cement warehouse workers and 82 age-matched individuals with no exposure to cement dust. Exfoliated buccal micronucleus cytome assay (BMCyt) was performed to analyze the genotoxic and cytotoxic effects caused by inhalation of cement dust. RESULTS: The frequency of various genotoxic and cytotoxic end markers (micronucleated cells [2-fold increase, p<0.001], nuclear buds [4-fold increase, p<0.001], binucleated cells [4-fold increase, p<0.001], karyorrhectic cells [2-fold increase, p<0.001], pyknotic cells [3-fold increase, p<0.001], and karyolytic cells [2-fold increase, p<0.001]) were higher in the exposed workers compared with unexposed group. Increase of these parameters represented an increased level of chromosomal damage, nuclear disintegration and increased cell death among exposed group compared with unexposed group. CONCLUSION: Continuous exposure to cement dust results in increased frequency of nuclear aberrations and cellular apoptosis. This may lead to defects in genome maintenance, accelerated ageing, increased chance of oral cancer and neurodegenerative disorders in those occupationally exposed to cement dust.


Assuntos
Dano ao DNA/efeitos dos fármacos , Poeira , Instabilidade Genômica/genética , Mucosa Bucal/citologia , Exposição Ocupacional/efeitos adversos , Adulto , Apoptose/efeitos dos fármacos , Aberrações Cromossômicas/induzido quimicamente , Humanos , Masculino , Testes para Micronúcleos/métodos , Pessoa de Meia-Idade
3.
Toxicol In Vitro ; 62: 104718, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31706955

RESUMO

Ketamine is a potent uncompetitive NMDA receptor antagonist that provides amnesia, analgesia, environmental dissociation and immobility, where it has its cytotoxic effect well described in the literature. However, the work on its genotoxic/mutagenic potentials are scarce and insufficient and does not allow a reasonable evaluation of its role. Thus, in the present work, we decided to evaluate the genotoxic and mutagenic effects of ketamine on human peripheral blood leukocytes (PBLs) and Salmonella typhimurium (TA98, TA97a, TA100, and TA102) through several well-established experimental protocols based on different parameters in the presence or not of exogenous metabolizing S9 fraction. Our data revealed that ketamine induces a weak cytotoxic effect on human PBLs after 24 h and is devoided of hemolytic effects. A small amount of DNA strand breaks levels were detected in the modified comet assay (employment of FPG enzyme) only at highest concentrations (500 and 700 µg/mL) of ketamine, highlighting our pro-oxidant data regarding ketamine. However, the oxidative DNA lesions were almost completely repaired which reflects in the lack of mutagenesis (micronuclei and chromosomal aberrations) on human PBLs and no increases in revertants numbers on S. typhimurium/microsome test (500 to 5000 µg/plate). In summary, ketamine is a weak oxidative DNA damaging agent and is devoid of mutagenic properties on eukaryotic and prokaryotic models.


Assuntos
Anestésicos Dissociativos/toxicidade , Ketamina/toxicidade , Leucócitos/efeitos dos fármacos , Mutagênicos/toxicidade , Salmonella typhimurium/efeitos dos fármacos , Salmonella typhimurium/genética , Apoptose/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Aberrações Cromossômicas/induzido quimicamente , Ensaio Cometa , Quebras de DNA , Dano ao DNA , Hemólise/efeitos dos fármacos , Humanos , Peroxidação de Lipídeos/efeitos dos fármacos , Testes de Mutagenicidade , Estresse Oxidativo
4.
J Oncol Pharm Pract ; 26(1): 212-215, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30854923

RESUMO

We report a case of acute myeloid leukemia with complex cytogenetic abnormalities suggestive of preexisting myelodysplastic syndrome in a patient with habitual ingestion of colloidal silver as nutritional supplement for over 10 years and the medical literature is reviewed.


Assuntos
Aberrações Cromossômicas/induzido quimicamente , Leucemia Mieloide Aguda/induzido quimicamente , Prata/efeitos adversos , Idoso , Suplementos Nutricionais/efeitos adversos , Humanos , Leucemia Mieloide Aguda/genética , Masculino
5.
Mutat Res ; 847: 403025, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31699346

RESUMO

An aneuploidy workgroup was established as part of the 7th International Workshops on Genotoxicity Testing. The workgroup conducted a review of the scientific literature on the biological mechanisms of aneuploidy in mammalian cells and methods used to detect chemical aneugens. In addition, the current regulatory framework was discussed, with the objective to arrive at consensus statements on the ramifications of exposure to chemical aneugens for human health risk assessment. As part of these efforts, the workgroup explored the use of adverse outcome pathways (AOPs) to document mechanisms of chemically induced aneuploidy in mammalian somatic cells. The group worked on two molecular initiating events (MIEs), tubulin binding and binding to the catalytic domain of aurora kinase B, which result in several adverse outcomes, including aneuploidy. The workgroup agreed that the AOP framework provides a useful approach to link evidence for MIEs with aneuploidy on a cellular level. The evidence linking chemically induced aneuploidy with carcinogenicity and hereditary disease was also reviewed and is presented in two companion papers. In addition, the group came to the consensus that the current regulatory test batteries, while not ideal, are sufficient for the identification of aneugens and human risk assessment. While it is obvious that there are many different MIEs that could lead to the induction of aneuploidy, the most commonly observed mechanisms involving chemical aneugens are related to tubulin binding and, to a lesser extent, inhibition of mitotic kinases. The comprehensive review presented here should help with the identification and risk management of aneugenic agents.


Assuntos
Rotas de Resultados Adversos , Aneuploidia , Doenças Genéticas Inatas/induzido quimicamente , Mitose/efeitos dos fármacos , Testes de Mutagenicidade/métodos , Mutagênicos/toxicidade , Neoplasias/induzido quimicamente , Animais , Aurora Quinase B/antagonistas & inibidores , Aurora Quinase B/fisiologia , Carcinógenos/toxicidade , Aberrações Cromossômicas/induzido quimicamente , Segregação de Cromossomos/efeitos dos fármacos , Cromossomos/efeitos dos fármacos , Genes Reporter , Doenças Genéticas Inatas/genética , Células Germinativas/efeitos dos fármacos , Células Germinativas/ultraestrutura , Humanos , Camundongos , Testes para Micronúcleos , Microtúbulos/efeitos dos fármacos , Mitose/fisiologia , Testes de Mutagenicidade/normas , Mutagênicos/análise , Neoplasias/genética , Não Disjunção Genética/efeitos dos fármacos , Gestão de Riscos/legislação & jurisprudência , Moduladores de Tubulina/toxicidade
6.
Environ Toxicol Pharmacol ; 72: 103267, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31586869

RESUMO

This work aimed to study the risk assessment procedures of a combination of single and repeated dose of the widely used pesticide, ethoprophos (Etho) and heavy metal cadmium (Cd), on the hematological, biochemical, reproduction and cytogenetic parameters in male mice. The results revealed that the sub-lethal dose (1/50 LD50) of the tested toxic substances (Etho and/or Cd) reduced the body and organ weights, the most hematological profile and the activity of acetylcholine esterase (AChE). The tested pollutants significantly increased the parameters of liver function, including aspartate aminotransferase (AST) and alanine aminotransferase (ALT), as well as renal function tests, including creatinine and urea. In addition, they have deleterious effects on reproductive function tests by stimulating the number of sperm abnormalities (SA) and cytogenetic assays by increasing the frequency of chromosomal abnormalities (CA) and the mitotic index (MI). The overall results of this exploratory study suggest that the co-existence of the two tested compounds (Etho and Cd) had the propensity to cause a more pronounced effect than that of each compound alone on all the battery measured biomarkers, especially in the repeated treatment (14 doses) than that in the single one. Also, the combination of a range of simple and sensitive assays as endpoints gives a comprehensive picture and provides better insights to evaluate the potential effects of other commonly encountered environmental pollutants.


Assuntos
Cádmio/toxicidade , Poluentes Ambientais/toxicidade , Compostos Organotiofosforados/toxicidade , Praguicidas/toxicidade , Acetilcolinesterase/metabolismo , Animais , Biomarcadores/metabolismo , Peso Corporal/efeitos dos fármacos , Células da Medula Óssea/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Encéfalo/enzimologia , Aberrações Cromossômicas/induzido quimicamente , Sinergismo Farmacológico , Rim/efeitos dos fármacos , Fígado/efeitos dos fármacos , Masculino , Camundongos , Tamanho do Órgão/efeitos dos fármacos , Espermatozoides/anormalidades , Espermatozoides/efeitos dos fármacos
7.
Methods Mol Biol ; 2031: 79-104, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31473955

RESUMO

Chromosome damage is a very important indicator of genetic damage relevant to environmental and clinical studies. Detailed descriptions of the protocols used for detection of chromosomal aberrations induced by genotoxic agents in vitro both in the presence or absence of rat liver-derived metabolizing systems are given in this chapter. Structural chromosomal aberrations that can be observed and quantified at metaphases are described here. For the detection of chromosomal damage (fragments or whole chromosome) in interphase, the micronucleus test can be used, and a description of this test is also presented. Criteria for determining a positive result using appropriate statistical methods are described.


Assuntos
Aberrações Cromossômicas/induzido quimicamente , Testes para Micronúcleos/métodos , Animais , Células CHO , Linhagem Celular , Cricetulus , Análise Citogenética/métodos , Metáfase , Mutagênicos/toxicidade , Coloração e Rotulagem/métodos
8.
Methods Mol Biol ; 2031: 135-146, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31473958

RESUMO

The presence of genotoxic agents in the environment may cause chromosomal mutations through different mechanisms, which are associated with serious health effects. Genotoxicity is commonly evaluated for the chemical safety assessment, in which the in vivo micronucleus test is paid more attention in the field of genotoxicity as compared to other toxicological endpoints. This assay is an in vivo cytogenetic test which uses erythrocytes in the bone marrow of rodents to detect chemical damage to the chromosomes or mitotic apparatus of mammalian cells. At the time of erythroblast development into a polychromatic erythrocyte (PCEs) in bone marrow, the main nucleus is extruded, so any micronucleus (MN) that has been formed may remain behind in the otherwise anucleated cytoplasm. The damage in the chromosome appears as a small additional nucleus and is readily identifiable by light microscope. An increase in the frequency of micronucleated polychromatic erythrocytes (MN PCEs) in treated animals is an indication of genotoxicity.


Assuntos
Medula Óssea/efeitos dos fármacos , Aberrações Cromossômicas/induzido quimicamente , Testes para Micronúcleos/métodos , Animais , Corantes Azur/análise , Medula Óssea/metabolismo , Células da Medula Óssea/efeitos dos fármacos , Células da Medula Óssea/metabolismo , Eritrócitos/efeitos dos fármacos , Eritrócitos/metabolismo , Camundongos , Micronúcleos com Defeito Cromossômico/induzido quimicamente , Coloração e Rotulagem/métodos
9.
Methods Mol Biol ; 2031: 147-163, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31473959

RESUMO

The micronucleus (MN) assay, applied in different surrogate tissues, is one of the best validated cytogenetic techniques for evaluating chromosomal damage in humans. The cytokinesis-block micronucleus cytome assay in peripheral blood lymphocytes (L-CBMNcyt) is the most frequently used method in biomonitoring human populations to evaluate DNA damage caused by exposure to genotoxic agents, micronutrient deficiency or excess and genetic instability. Furthermore, recent scientific evidence suggests an association between an increased MN frequency in lymphocytes and risk of cancer and other age-related degenerative diseases. The micronucleus cytome assay applied in buccal exfoliated cells (BMNCyt), provides a complementary method for measuring DNA damage and cytotoxic effects in an easily accessible tissue not requiring ex vivo/in vitro culture. The protocol for L-CBMNcyt described here, refers to the use of ex vivo whole blood method, involving 72 h of culture with the block of cytokinesis starting at 44 h. BMNCyt protocol reports the established method for sample collection, processing, slide preparation and scoring.


Assuntos
Linfócitos/efeitos dos fármacos , Testes para Micronúcleos/métodos , Mucosa Bucal/efeitos dos fármacos , Mutagênicos/toxicidade , Técnicas de Cultura de Células/métodos , Células Cultivadas , Aberrações Cromossômicas/induzido quimicamente , Citocinese/efeitos dos fármacos , Dano ao DNA/efeitos dos fármacos , Humanos , Linfócitos/citologia , Linfócitos/metabolismo , Mucosa Bucal/citologia , Mucosa Bucal/metabolismo , Coloração e Rotulagem/métodos
10.
Methods Mol Biol ; 2031: 209-234, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31473962

RESUMO

In the past two decades, comparative genomic hybridization (CGH) and array CGH have become indispensable tools in clinical diagnostics and toxicological risk assessment. Initially developed for the genome-wide screening of chromosomal imbalances, that is, copy-number variations in tumor cells, both CGH and array CGH have been employed in genotoxicology and most recently in toxicogenomics. The latter allows a multi-end point analysis of how particular genes react to toxic agents, revealing changes in signaling pathways and other underlying molecular mechanisms. This chapter provides background on the use of CGH and array CGH in the context of genotoxicology, and also a protocol for conventional CGH, so that the basic principles of this methodology can be better understood. Conventional and array CGH investigate DNA expression patterns, copy-number variations across the whole genome, and loss of heterozygosity after genotoxic damage. Array CGH is still cost-intensive but produces exponentially more data, requiring suitable analytical algorithms and sophisticated bioinformatic analysis. As toxicogenomics is an emerging sub-discipline of toxicology research, effectively evaluating toxicogenomic microarray data can be hugely advantageous for human risk assessment, even though international regulatory guidelines on toxicogenomics have yet to be fully agreed and implemented.


Assuntos
Hibridização Genômica Comparativa/métodos , Testes de Mutagenicidade/métodos , Animais , Aberrações Cromossômicas/induzido quimicamente , Variações do Número de Cópias de DNA/efeitos dos fármacos , Genômica/métodos , Humanos
11.
Ecotoxicol Environ Saf ; 183: 109528, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31404724

RESUMO

The aim of this study was to evaluate the cytotoxic effect of different concentrations of chlorpyrifos (CPF), using L. culinaris apical cells as a biological indicator. L. culinaris seeds were exposed to different concentrations of chlorpyrifos (0, 1, 3, 5, 7, 8, 10 and 15 mg L-1) and a control solution based on distilled water. Subsequently, root growth was measured during 24, 48 and 72 h. Therefore, the mitotic index (MI) and the number of cellular abnormalities were determined at 72 h. According to the obtained results, a decrease in root size was observed in the concentrations of T5 (8 mg L-1) and T6 (10 mg L-1). On the other hand, it was evidenced that, through all the evaluated concentrations, the inhibition of mitosis in the concentrations of T5 (8 mg L-1), T6 (10 mg L-1) and T7 (15 mg L-1) was greater than 50%. Additionally, a variety of chromosomal abnormalities were reported, such as Micronuclei, sticky chromosomes in anaphase, chromosome disruption, irregular anaphase, nucleus absence, nuclear lesions, chromosomes grouped in metaphase, anaphase bridges, metaphase sticky chromosomes, present in all concentrations evaluated. Consequently, the presence of micronuclei in the concentrations of 8 mg L-1, 10 mg L-1 and 15 mg L-1 indicates that the CPF is a highly cytotoxic substance to L. culinaris. Therefore, L. culinaris is a plant species that offers a feasible experimental model to be implemented in laboratory studies with the purpose to evaluate the cytotoxic effect of pesticides.


Assuntos
Clorpirifos/toxicidade , Biomarcadores Ambientais/efeitos dos fármacos , Lens (Planta)/efeitos dos fármacos , Mitose/efeitos dos fármacos , Praguicidas/toxicidade , Núcleo Celular/efeitos dos fármacos , Núcleo Celular/genética , Aberrações Cromossômicas/induzido quimicamente , Relação Dose-Resposta a Droga , Biomarcadores Ambientais/genética , Lens (Planta)/citologia , Lens (Planta)/genética , Índice Mitótico
12.
Toxicol Ind Health ; 35(8): 548-557, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31370753

RESUMO

Metal oxide nanoparticles (NPs) have widespread uses ranging from nanoelectronics to nanotherapeutics. Because of their expanding industrial applications, a better understanding of their toxicity is needed. So far, limited reports are available on chromium oxide NPs (Cr2O3 NPs) toxicity. In this work, Cr2O3 NPs were synthesized and characterized in a sequential manner using X-ray diffraction (XRD), Fourier transform infrared (FTIR) spectroscopy, and transmission electron microscopy. Dose- and time-dependent toxicity assessment of Cr2O3 NPs was carried out in Wistar rats by examining liver function biomarkers, tissue histopathology, micronuclei (MN) formation, and chromosomal aberrations (CAs) in bone marrow along with sperm abnormalities. The results of this study demonstrated typical XRD and FTIR patterns of Cr2O3 NPs with a size of approximately 23.47 nm. Animals exposed to Cr2O3 NPs, exhibited a significant increase in aspartate transaminase, alanine transaminase, alkaline phosphatase, gamma glutamyltransferase, and total bilirubin, signifying liver injury. Histopathology data also supported the marked alterations in the liver biochemistry of NPs-exposed animals. Further, an increase in the frequency of MN, CA, and sperm abnormalities suggested Cr2O3 NPs-mediated genotoxicity. It is, therefore, suggested that possible safety issues of Cr2O3 NPs should be addressed promptly with limited future use in occupational settings.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas/etiologia , Compostos de Cromo/toxicidade , Aberrações Cromossômicas/induzido quimicamente , Nanopartículas Metálicas/toxicidade , Administração Oral , Animais , Medula Óssea/efeitos dos fármacos , Doença Hepática Induzida por Substâncias e Drogas/patologia , Compostos de Cromo/administração & dosagem , Relação Dose-Resposta a Droga , Fígado/efeitos dos fármacos , Fígado/patologia , Masculino , Nanopartículas Metálicas/administração & dosagem , Testes para Micronúcleos , Ratos , Ratos Wistar , Espermatozoides/efeitos dos fármacos
13.
Mutat Res ; 842: 132-145, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31255221

RESUMO

Nanoparticles (NPs) are an emerging environmental threat. However, studies of NPs in different environmental components are limited. In this review, we discuss studies that have evaluated the genotoxicity of NPs in higher plants. Among the 29 studies reviewed, silver NPs were most studied (n = 7 articles), with fewer studies reporting the genotoxicity of carbon nanotubes (n = 3), titanium dioxide NPs (n = 4), and zinc oxide NPs (n = 3). Most of the genotoxicity studies were performed in the model plant systems Allium sp (n = 22), Nicotiana sp (n = 4) and Vicia sp (n = 4) using chromosome aberration (n = 22), micronucleus (n = 15) and comet assays (n = 14). Genotoxicity was observed in most of the studies; however, many studies did consider key determinants of NP toxicity such as particle characterization, dissolution, and uptake. From this review, we propose a set of guidelines that should be considered when reporting results of NP toxicity in plants.


Assuntos
Nanopartículas Metálicas/toxicidade , Mutagênicos/toxicidade , Plantas/efeitos dos fármacos , Aberrações Cromossômicas/induzido quimicamente , Ensaio Cometa/métodos , Dano ao DNA/efeitos dos fármacos , Testes para Micronúcleos/métodos , Nanotubos de Carbono/toxicidade , Titânio/toxicidade , Óxido de Zinco/toxicidade
14.
Int J Radiat Oncol Biol Phys ; 105(3): 548-558, 2019 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-31271827

RESUMO

PURPOSE: Human papillomavirus negative (HPV-ve) head and neck squamous cell carcinoma (HNSCC) has a poor prognosis compared with HPV+ve HNSCCs. Expression of p16 in HPV+ve HNSCC is thought to mediate radiosensitivity via inhibition of cyclin-dependent kinase (CDK) 4/6. We used a clinically approved CDK4/CDK6 inhibitor, palbociclib, and assessed its effect on radiosensitivity in HNSCC. METHODS AND MATERIALS: The effect of palbociclib on radiosensitivity was determined in HPV-ve and HPV+ve HNSCC cell lines using colony survival assays, immunofluorescent staining of repair proteins, homologous recombination assays, cell cycle, and metaphase spread analyses. RESULTS: Only HPV-ve HNSCC cells were radiosensitized by palbociclib, which also occurred at hypoxic levels associated with radioresistance. Palbociclib led to decreased induction of BRCA1 and RAD51 after irradiation. Homologous recombination was diminished and repair of radiation-induced DNA damage was delayed in the presence of palbociclib, leading to increased chromosomal damage. Failure to repair radiation-induced damage led to cell death as a result of mitotic catastrophe. CONCLUSIONS: Here, we highlight a therapeutic strategy to improve the radiosensitivity of HPV-ve HNSCC, a patient group that has an unmet and urgent need for improved radiation therapy efficacy.


Assuntos
Quinase 4 Dependente de Ciclina/antagonistas & inibidores , Quinase 6 Dependente de Ciclina/antagonistas & inibidores , Neoplasias de Cabeça e Pescoço/radioterapia , Piperazinas/uso terapêutico , Inibidores de Proteínas Quinases/uso terapêutico , Piridinas/uso terapêutico , Tolerância a Radiação , Radiossensibilizantes/uso terapêutico , Carcinoma de Células Escamosas de Cabeça e Pescoço/radioterapia , Proteína BRCA1/metabolismo , Ciclo Celular , Morte Celular , Linhagem Celular Tumoral , Aberrações Cromossômicas/induzido quimicamente , Inibidor p16 de Quinase Dependente de Ciclina/metabolismo , Reparo do DNA/efeitos dos fármacos , Proteínas de Ligação a DNA/metabolismo , Neoplasias de Cabeça e Pescoço/virologia , Recombinação Homóloga , Humanos , Proteínas de Neoplasias/metabolismo , Papillomaviridae , Fosforilação , Rad51 Recombinase/metabolismo , Proteína do Retinoblastoma/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/virologia , Hipóxia Tumoral , Ensaio Tumoral de Célula-Tronco
15.
Environ Sci Pollut Res Int ; 26(18): 18403-18410, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31049867

RESUMO

Nanoparticles are very effective compounds to transform and detoxicate common environmental contaminants. For this reason, crude urban liquid wastewater sludges were treated by silver nanoparticles (Ag-NPs, 100 nm) for 24 h. Both Ag-NPs' treated and untreated sludges were examined for the evaluation if there are possible mutagenic/anti-mutagenic, cytotoxic, and genotoxic/anti-genotoxic effects by Ames and Allium cepa tests. The results were then subjected to statistical analyses by using SPSS software and p < 0.05 was accepted as a significant value. The data obtained from the Ames test showed that while untreated crude liquid sludge had a significant mutagenic effect, Ag-NP-treated one decreased its mutagenicity. Similar effects were also observed in the chromosome aberration-Allium cepa tests. Significant chromosome aberrations observed were C-metaphase, sticky metaphase, sticky anaphase, anaphase bridge, vagrant chromosome, and multipolar anaphases. Both tests demonstrated that silver nanoparticle treatment decreased the major mutagenicity and genotoxicity detected in the liquid wastewater sludges.


Assuntos
Nanopartículas Metálicas/química , Mutagênicos/toxicidade , Esgotos/química , Prata/química , Eliminação de Resíduos Líquidos/métodos , Águas Residuárias/toxicidade , Aberrações Cromossômicas/induzido quimicamente , Dano ao DNA , Testes de Mutagenicidade , Cebolas/efeitos dos fármacos , Cebolas/genética , Águas Residuárias/química
16.
Environ Sci Pollut Res Int ; 26(20): 20981-20988, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31115805

RESUMO

The impact evaluation of pesticide exposure is conducted using combined data from biomonitoring and environmental monitoring. Damage to the human genome is, probably, the leading cause of chronic-degenerative disorders, reproductive toxicology, and developmental problems. Although the general population is exposed to pesticides, workers in the agrochemical industry and farmers represent a high-risk group due to the occupational and environmental exposure. The aim of this study is to determine whether occupational exposure to agrochemicals in Córdoba (Argentina) constitute a factor of genotoxic damage. The study was conducted in 30 pesticide applicators from the province of Córdoba. Chromosomal aberrations (CAs), micronuclei (MN), and comet assays (CO) were performed. The current study shows that occupational exposure to pesticides increases values of CAs, MN, and DNA fragmentation biomarkers, all indicators of damage to the genetic material. Evidence suggests that chronic exposure to pesticides is a potential risk to workers health.


Assuntos
Doenças dos Trabalhadores Agrícolas/epidemiologia , Dano ao DNA/efeitos dos fármacos , Exposição Ocupacional/efeitos adversos , Praguicidas/toxicidade , Adulto , Argentina/epidemiologia , Biomarcadores/sangue , Colinesterases/sangue , Colinesterases/toxicidade , Aberrações Cromossômicas/induzido quimicamente , Aberrações Cromossômicas/estatística & dados numéricos , Monitoramento Ambiental/estatística & dados numéricos , Humanos , Masculino , Exposição Ocupacional/estatística & dados numéricos , Praguicidas/sangue
17.
Environ Sci Pollut Res Int ; 26(18): 18208-18229, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31041706

RESUMO

Severity of clinical expression and high mortality could not facilitate establishing exposure index/association following MIC disaster in Bhopal. Mortality-based exposure stratification was critiqued by the International Medical Commission on Bhopal (IMCB). IMCB stratified exposure considering distance as surrogate at 2 km intervals after 10 years. The first follow-up cytogenetic screening of the pre-screened survivors after 30 years has demonstrated chromosome abnormalities (CA). Exposure stratification was attempted considering cytogenetic screening conducted during 1986-1988. Elevation of CA appeared proportional to exposure status and authenticated the initial mortality-based stratification. The one-on-one comparison of the previous and present cytogenetics has described the individual response to MIC exposure over 30 years. Chi-square test has been carried out for checking the cytogenetic changes at the individual level statistically, which revealed that differences of chromosomal aberrations collected immediately post-disaster and 30 years later are nonsignificant. The prominence of interindividual variation was noticed in general. The impact of overall exposure was higher in males. Constitutional abnormalities in 8.5% of the study population, including translocation, inversion, deletion, fragile sites, etc., necessitate screening of blood-linked members. The incidence of acrocentric association was prominent in the study population. Normal karyotype in children born to severely exposed parents with congenital anomalies indicates necessity of molecular karyotyping and/or screening of mutations. The study highlights follow-up of the health of the index cases at shorter (3-6 months) intervals. This comprehensive spectrum of cytogenetic report highlights immediate post-disaster chromosomal aberrations, the changes that occurred over 30 years in conjunction with other environmental factors at the individual level, constitutive genomic aberrations, polymorphic variations, and chromosomal patterns in congenitally malformed children of the survivors, which collectively indicate the possibility of acquisition/persistence of stable aberrations in MIC-exposed lymphocytes through interaction with environmental/biological confounders.


Assuntos
Aberrações Cromossômicas/induzido quimicamente , Análise Citogenética , Desastres , Exposição Ambiental , Isocianatos/toxicidade , Mutagênicos/toxicidade , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Exposição Ambiental/normas , Feminino , Seguimentos , Humanos , Índia , Linfócitos/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Fatores Sexuais
18.
Zhonghua Yu Fang Yi Xue Za Zhi ; 53(4): 371-375, 2019 Apr 06.
Artigo em Chinês | MEDLINE | ID: mdl-30982270

RESUMO

Objective: To study on the genomic stability of male workers engaged in e-waste dismantling area in Tianjin. Methods: In 2016, an e-waste dismantling area in Tianjin and an area 50 km away from the e-waste dismantling area (no e-waste or other chemical, industrial and agricultural pollution nearby) were selected as the study area and the reference area. Male residents of the study area and male farmers who planted vegetables, fruits, and crops in the reference area were selected as the exposed and reference group by using the convenient sampling method. The exposed group included 146 workers who engaged in e-waste recycling work more than 1 year. The reference group included 121 farmers who never engaged in e-waste recycling work. Questionnaires were used to collect information of all subjects. The semen and peripheral blood were also collected. Trace elements and polychlorinated biphenyl concentration in blood were detected. DNA damage in peripheral blood and sperm was detected, and gene expression was analyzed. DNA damage was assessed using tail DNA% (TDNA%), tail moment (TM) and olive tail moment (OTM) of comet assay. Results: The ages of the exposed group and the reference group were (33.6±12.1) and (33.9±11.9) years old, respectively. The proportions of subjects with exposure time of ≤3, 4-6, ≥7 years were 43% (63 cases), 26% (53 cases) and 21% (30 cases), respectively. The Pb and polychlorinated biphenyl(PCB) concentrations in the exposed group [(90.4±15.3) µg/ml and (101±30) ng/ml, respectively] were higher than those in the reference group [Pb and PCB concentrations were (60.2±8.9) µg/ml, and (2.5±1.4) ng/ml, respectively (both P values <0.05)]. The TDNA%, TM and OTM of peripheral blood and sperm in the exposed group were 5.9%±0.3% and 2.6%±0.90%, 0.93±0.16 and 0.51±0.20, 0.82±0.09 and 0.56±0.07, respectively, which were all higher than those in the reference group [TDNA%, TM and OTM of peripheral blood and sperm were 1.8%±0.2% and 1.9%±0.2%, 0.21±0.04 and 0.32±0.10, 0.19±0.03 and 0.20±0.08, respectively (all P values <0.001)]. The results of gene expression showed that 20 differentially expressed genes, including 13 up-regulated genes and 7 down-regulated genes, were detected in the exposed group compared with the reference group. Conclusion: There are obvious DNA damage and DNA repair gene disorder in male workers of an e-waste dismantling area in Tianjin. The current operation mode brings potential health risks to workers.


Assuntos
Aberrações Cromossômicas/induzido quimicamente , Dano ao DNA/efeitos dos fármacos , Resíduo Eletrônico , Exposição Ambiental/efeitos adversos , Exposição Ocupacional , Bifenilos Policlorados/sangue , Reciclagem , Sêmen/efeitos dos fármacos , Adulto , Instabilidade Genômica , Humanos , Masculino , Pessoa de Meia-Idade , Vigilância da População , Adulto Jovem
19.
Int J Mol Med ; 43(6): 2491-2498, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31017265

RESUMO

Nucleos(t)ide analogues (NAs) are currently the most important anti­viral treatment option for patients with chronic hepatitis B (CHB). Adefovir dipivoxil (ADV), a diester pro­drug of adefovir, has been widely used for the clinical therapy of hepatitis B virus infection. It has been previously reported that adefovir induced chromosomal aberrations (CAs) in the in vitro human peripheral blood lymphocyte assay, while the genotoxic mechanism remains elusive. To evaluate the possible mechanisms, the genotoxic effects of ADV on the TK6 and DT40 cell lines, as well as DNA repair­deficient variants of DT40 cells, were assessed in the present study. A karyotype assay revealed ADV­induced CAs, particularly chromosomal breaks, in wild­type DT40 and TK6 cells. A γ­H2AX foci formation assay confirmed the presence of DNA damage following treatment with ADV. Furthermore, Brca1­/­ DT40 cells exhibited an increased sensitivity to ADV, while the knockdown of various other DNA damage­associated genes did not markedly affect the sensitivity. These comprehensive genetic studies identified the genotoxic capacity of ADV and suggested that Brca1 may be involved in the tolerance of ADV­induced DNA damage. These results may contribute to the development of novel drugs against CHB with higher therapeutic efficacy and less genotoxicity.


Assuntos
Adenina/análogos & derivados , Antivirais/efeitos adversos , Proteína BRCA1/metabolismo , Aberrações Cromossômicas/induzido quimicamente , Dano ao DNA/efeitos dos fármacos , Organofosfonatos/efeitos adversos , Adenina/efeitos adversos , Proteína BRCA1/genética , Linhagem Celular , Deleção de Genes , Hepatite B Crônica/tratamento farmacológico , Humanos
20.
J Ethnopharmacol ; 237: 171-181, 2019 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-30890359

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Cynarin is an artichoke phytochemical that possesses a variety of pharmacological features including free-radical scavenging and antioxidant activity. The origin of artichoke species appears to be Mediterranean region. Two of these species, globe artichoke (Cynara cardunculus var. scolymus L.) and cardoon (Cynara cardunculus var. altilis DC), are widely cultivated and consumed. This vegetable, as the basis of the mediterranean diet, has been used as herbal medicine for its therapeutic effects since ancient times. Therefore, this study was performed to determine genotoxic and antigenotoxic effects of cynarin against MMC (mitomycin C) and H2O2 (hydrogen peroxide) induced genomic instability using chromosome aberrations (CAs), sister chromatid exchanges (SCEs), micronucleus (MN), and comet assays in human lymphocytes. MATERIALS AND METHODS: Lymphocytes obtained from two healthy volunteers (1 male and 1 female) were exposed to different concentrations of cynarin (12-194 µM) alone and the combination of cynarin and MMC (0.60 µM) or cynarin and H2O2 (100 µM, only for comet assay). RESULTS: Cynarin alone did not induce significant genotoxic effect in the CA, SCE (except 194 µM), MN, and comet assays. The combination of some concentrations of cynarin and MMC decreased the frequency of CAs, SCEs and MN induced by MMC. Furthermore, the combination of cynarin and H2O2 reduced all comet parameters at all the concentrations compared to H2O2 alone. While the highest concentrations of cynarin significantly decreased mitotic index (MI), the combination of cynarin and MMC increased the reduction of MI induced by MMC alone. CONCLUSION: All the results obtained in this study demonstrated that cynarin exhibited antigenotoxic effects rather than genotoxic effects. It is believed that cynarin can act as a potential chemo-preventive against genotoxic agents.


Assuntos
Anticarcinógenos/farmacologia , Cinamatos/farmacologia , Adulto , Células Cultivadas , Aberrações Cromossômicas/induzido quimicamente , Ensaio Cometa , Dano ao DNA , Feminino , Instabilidade Genômica/efeitos dos fármacos , Humanos , Peróxido de Hidrogênio , Linfócitos/efeitos dos fármacos , Masculino , Testes para Micronúcleos , Mitomicina , Mutagênicos , Adulto Jovem
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