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1.
Nutrients ; 12(5)2020 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-32384595

RESUMO

Nigella sativa (N. sativa) is a medicinal plant used for its therapeutic pharmacological effects such as anti-inflammatory, antioxidant, anticancer, antidiabetic, and immunomodulation. This study explored the anti-cytotoxic and anti-genotoxic effect of N. sativa through a micronucleus test (MNT) of BALB/c mice peripheral blood. Using 6-to-8-week-old healthy male BALB/c mice, four groups were formed: (1) Control (sterile water), single-dose 2 mg/kg/intraperitoneal (i.p); (2) N. sativa oil, 500 mg/kg/24 h/7 days/i.p; (3) Cisplatin (CP), single-dose 2 mg/kg/subcutaneous (s.c); (4) N. sativa + CP with their respective dosage. When evaluating polychromatic erythrocytes (PCE), a biomarker of cytotoxicity, the group treated with N. sativa + CP experienced an increase in the frequency of PCE, which demonstrated the recovery of bone marrow and modulation of cell proliferation. The analysis of micronucleated polychromatic erythrocytes (MNPCE), an acute genotoxicity biomarker, showed similar frequency of MNPCE within the groups except in CP, but, in the N. sativa + CP group, the frequency of MNPCE decreased and then regulated. Finally, the frequency of micronucleated erythrocytes (MNE), a biomarker of genotoxicity, the supplementation of N. sativa oil did not induce genotoxic damage in this model. Thus, we conclude that N. sativa has both cytoprotective, genoprotective effects and modulates cell proliferation in BALB/c mice.

2.
Oxid Med Cell Longev ; 2019: 4528241, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31428226

RESUMO

During the last 3 decades, there has been a slow advance to obtain new treatments for malignant melanoma that improve patient survival. In this work, we present a systematic study focused on the antiproliferative and antitumour effect of AgNPs. These nanoparticles are fully characterized, are coated with polyvinylpyrrolidone (PVP), and have an average size of 35 ± 15 nm and a metallic silver content of 1.2% wt. Main changes on cell viability, induction of apoptosis and necrosis, and ROS generation were found on B16-F10 cells after six hours of exposure to AgNPs (IC50 = 4.2 µg/mL) or Cisplatin (IC50 = 2.0 µg/mL). Despite the similar response for both AgNPs and Cisplatin on antiproliferative potency (cellular viability of 53.95 ± 1.88 and 53.62 ± 1.04) and ROS production (20.27 ± 1.09% and 19.50 ± 0.35%), significantly different cell death pathways were triggered. While AgNPs induce only apoptosis (45.98 ± 1.88%), Cisplatin induces apoptosis and necrosis at the same rate (22.31 ± 1.72% and 24.07 ± 1.10%, respectively). In addition to their antiproliferative activity, in vivo experiments showed that treatments of 3, 6, and 12 mg/kg of AgNPs elicit a survival rate almost 4 times higher (P < 0.05) compared with the survival rate obtained with Cisplatin (2 mg/kg). Furthermore, the survivor mice treated with AgNPs do not show genotoxic damage determined by micronuclei frequency quantification on peripheral blood cells. These results exhibit the remarkable antitumour activity of a nongenotoxic AgNP formulation and constitute the first advance toward the application of these AgNPs for melanoma treatment, which could considerably reduce adverse effects provoked by currently applied chemotherapeutics.


Assuntos
Melanoma Experimental/tratamento farmacológico , Nanopartículas Metálicas/uso terapêutico , Prata/química , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Cisplatino/uso terapêutico , Dano ao DNA/efeitos dos fármacos , Eritrócitos/citologia , Eritrócitos/efeitos dos fármacos , Eritrócitos/metabolismo , Estimativa de Kaplan-Meier , Masculino , Melanoma Experimental/mortalidade , Melanoma Experimental/patologia , Nanopartículas Metálicas/química , Nanopartículas Metálicas/toxicidade , Camundongos , Camundongos Endogâmicos C57BL , Espécies Reativas de Oxigênio/metabolismo
4.
Clin Rev Allergy Immunol ; 52(1): 125-132, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28004375

RESUMO

Gorham-Stout disease (GSD) is a rare condition of osteolysis with excessive lymphangiogenesis within bone tissue. The etiology of this condition remains unknown but seems to affect mainly children and young adults of both genders all over the world. Unfortunately, there is no standardized method for diagnosis; however, histopathology remains as the gold standard. This condition is often misdiagnosed due to its varying clinical presentations from case-to-case. Here, we report the case of an 8-year-old girl who presented with chronic mandibular pain during mastication and received multiple antibiotic treatment due to infectious origin suspicion. After integrating information from clinical manifestations, radiographic, laboratory, and histopathology information, she was diagnosed with GSD. Additionally, due to the lack of literature with respect to insights into biological mechanisms and standardized treatment for this condition, we underwent a literature revision to provide information related to activation of cells from the immune system, such as macrophages, T-cells, and dendritic cells, and their contribution to the lymphangiogenesis, angiogenesis, and osteoclastogenic process in GSD. It is important to consider these mechanisms in patients with GSD, especially since new studies performed in earlier stages are required to confirm their use as novel diagnostic tools and find new possibilities for treatment.


Assuntos
Osteólise Essencial/patologia , Criança , Feminino , Humanos , Mandíbula/anormalidades , Osteólise Essencial/diagnóstico
5.
J Toxicol ; 2016: 7934257, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26981119

RESUMO

Feminization of the agricultural labor is common in Mexico; these women and their families are vulnerable to several health risks including genotoxicity. Previous papers have presented contradictory information with respect to indirect exposure to pesticides and DNA damage. We aimed to evaluate the genotoxic effect in buccal mucosa from female farmers and children, working in the agricultural valley of Maneadero, Baja California. Frequencies of micronucleated cells (MNc) and nuclear abnormalities (NA) in 2000 cells were obtained from the buccal mucosa of the study population (n = 144), divided in four groups: (1) farmers (n = 37), (2) unexposed (n = 35), (3) farmers' children (n = 34), and (4) unexposed children (n = 38). We compared frequencies of MNc and NA and fitted generalized linear models to investigate the interaction between these variables and exposition to pesticides. Differences were found between farmers and unexposed women in MNc (p < 0.0001), CC (p = 0.3376), and PN (p < 0.0001). With respect to exposed children, we found higher significant frequencies in MNc (p < 0.0001), LN (p < 0.0001), CC (p < 0.0001), and PN (p < 0.004) when compared to unexposed children. Therefore working as a farmer is a risk for genotoxic damage; more importantly indirectly exposed children were found to have genotoxic damage, which is of concern, since it could aid in future disturbances of their health.

6.
Oral Maxillofac Surg ; 20(1): 1-7, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26556782

RESUMO

The purpose of the present article was to present a clinical case of an 11-year-old girl with peripheral ossifying fibroma (POF). Additionally, after performing a literature review, we identified clinical information that occurs more frequently in association with POF, such evidence would help professionals in yielding a specific diagnosis and tailor a more specific therapeutic approach with the objective to decrease morbidities' associated with POF. This lesion represents the third most common lesion of all localized reactive hyperplastic lesions. Clinical aspects related to this pathology include the fact that it occurs most frequently in women between the first and second decades of life. It affects anterior maxillary region and interferes with normal functioning of this anatomical structure. After conducting the literature search, we found that it can also be presented in a considerable number of males with pain and hyperemia being the most common clinical manifestations. We found that often clinical cases are presented with incomplete information. It is important that in order to get to a consensus with respect to updates about information related to this lesion, new case series that include complete clinical information, radiographic analysis, and histopathology tests could be presented.


Assuntos
Neoplasias Ósseas/diagnóstico , Fibroma Ossificante/diagnóstico , Neoplasias Maxilares/diagnóstico , Biópsia , Neoplasias Ósseas/patologia , Neoplasias Ósseas/cirurgia , Criança , Diagnóstico Diferencial , Feminino , Fibroma Ossificante/patologia , Fibroma Ossificante/cirurgia , Humanos , Masculino , Maxila/patologia , Maxila/cirurgia , Neoplasias Maxilares/patologia , Neoplasias Maxilares/cirurgia , Radiografia Panorâmica , Tomografia Computadorizada por Raios X
7.
Biomed Res Int ; 2015: 194031, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26339592

RESUMO

Autoimmune diseases (AD) are classified into organ-specific, systemic, and mixed; all forms of AD share a high risk for cancer development. In AD a destructive immune response induced by autoreactive lymphocytes is started and continues with the production of autoantibodies against different targets; furthermore apoptosis failure and loss of balance in oxidative stress as a consequence of local or systemic inflammation are common features seen in AD as well. Micronucleus (MN) assay can be performed in order to evaluate loss of genetic material in a clear, accurate, fast, simple, and minimally invasive test. The MN formation in the cytoplasm of cells that have undergone proliferation is a consequence of DNA fragmentation during mitosis and the appearance of small additional nuclei during interphase. The MN test, widely accepted for in vitro and in vivo genotoxicity research, provides a sensitive marker of genomic damage associated to diverse conditions. In here, we present a review of our work and other published papers concerning genotoxic effect in AD, identified by means of the MN assay, with the aim of proposing this tool as a possible early biomarker for genotoxic damage, which is a consequence of disease progression. Additionally this biomarker could be used for follow-up, to asses genome damage associated to therapies.


Assuntos
Doenças Autoimunes/genética , Dano ao DNA/efeitos dos fármacos , Linfócitos/efeitos dos fármacos , Testes para Micronúcleos , Neoplasias/genética , Apoptose/efeitos dos fármacos , Doenças Autoimunes/imunologia , Doenças Autoimunes/patologia , Carcinógenos/toxicidade , Núcleo Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Fragmentação do DNA/efeitos dos fármacos , Mitose/efeitos dos fármacos , Mutagênicos/toxicidade , Neoplasias/induzido quimicamente , Neoplasias/patologia , Estresse Oxidativo/efeitos dos fármacos
8.
PLoS One ; 10(8): e0131548, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26244938

RESUMO

BACKGROUND: An estimated 800,000 people worldwide are occupationally exposed to welding-fumes. Previous studies show that the exposure to such fumes is associated with damage to genetic material and increased cancer risk. In this study, we evaluate the genotoxic effect of welding-fumes using the Micronucleus Test on oral mucosa cells of Mexican welders. MATERIAL AND METHODS: We conducted a cross-sectional, matched case-control study of n = 66 (33 exposed welders, and 33 healthy controls). Buccal mucosa smears were collected and stained with acridine orange, observed under 100x optical amplification with a fluorescence lamp, and a single-blinded observer counted the number of micronuclei and other nuclear abnormalities per 2,000 observed cells. We compared the frequencies of micronuclei and other nuclear abnormalities, and fitted generalised linear models to investigate the interactions between nuclear abnormalities and the exposure to welding-fumes, while controlling for smoking and age. RESULTS: Binucleated cells and condensed-chromatin cells showed statistically significant differences between cases and controls. The frequency of micronuclei and the rest of nuclear abnormalities (lobed-nuclei, pyknosis, karyolysis, and karyorrhexis) did not differ significantly between the groups. After adjusting for smoking, the regression results showed that the occurrence of binucleated cells could be predicted by the exposure to welding-fumes plus the presence of tobacco consumption; for the condensed-chromatin cells, our model showed that the exposure to welding-fumes is the only reliable predictor. CONCLUSIONS: Our findings suggest that Mexican welders who are occupationally exposed to welding-fumes have increased counts of binucleated and condensed-chromatin cells. Nevertheless, the frequencies of micronuclei and the rest of nuclear abnormalities did not differ between cases and controls. Further studies should shed more light on this subject.


Assuntos
Dano ao DNA , Micronúcleos com Defeito Cromossômico/induzido quimicamente , Mucosa Bucal/patologia , Exposição Ocupacional/efeitos adversos , Soldagem , Estudos de Casos e Controles , Núcleo Celular , Estudos Transversais , Humanos , Masculino , México , Testes para Micronúcleos
9.
J Chemother ; 27(2): 87-93, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24548095

RESUMO

Sporotrichosis is a cutaneous fungal infection caused by Sporothrix schenckii. It is known to be mainly contained by Th1 responses. As IL-12 is crucial for Th1 response, we investigated if treatment with recombinant murine IL-12 (rmIL-12) promoted Th1 immunity and/or clinical improvement in an experimental sporotrichosis gerbil model. Gerbils were inoculated with S. schenckii in the footpad and treated with rmIL-12. Seven days post infection there was a significant increase in macrophage phagocytosis and oxidative burst, and in delayed-type hypersensitivity (DTH) reaction in rmIL-12 treated gerbils, as well as a ∼10-fold increase of serum IFN-gamma and a decrease of IL-4 and IL-10. Moreover, rmIL-12 substantially decreased (∼70%) S. schenckii burden in liver and spleen and improved the clinical outcome preventing footpad ulcer and tail nodules observed in untreated gerbils. Our study demonstrates that rmIL-12 promotes Th1 immune response against S. schenckii favouring its clearance and preventing clinical symptoms.


Assuntos
Imunidade Inata/efeitos dos fármacos , Fatores Imunológicos/uso terapêutico , Interleucina-12/uso terapêutico , Macrófagos Peritoneais/efeitos dos fármacos , Sporothrix/imunologia , Esporotricose/tratamento farmacológico , Células Th1/efeitos dos fármacos , Animais , Antifúngicos/metabolismo , Antifúngicos/uso terapêutico , Células Cultivadas , Técnicas de Cocultura , Hipersensibilidade a Drogas/imunologia , Hipersensibilidade a Drogas/microbiologia , Hipersensibilidade a Drogas/patologia , Hipersensibilidade a Drogas/prevenção & controle , Gerbillinae , Imunidade Celular/efeitos dos fármacos , Fatores Imunológicos/genética , Fatores Imunológicos/metabolismo , Interleucina-12/genética , Interleucina-12/metabolismo , Fígado/efeitos dos fármacos , Fígado/imunologia , Fígado/microbiologia , Macrófagos Peritoneais/imunologia , Macrófagos Peritoneais/microbiologia , Macrófagos Peritoneais/patologia , Masculino , Camundongos , Fagocitose/efeitos dos fármacos , Proteínas Recombinantes/metabolismo , Proteínas Recombinantes/uso terapêutico , Explosão Respiratória/efeitos dos fármacos , Organismos Livres de Patógenos Específicos , Baço/efeitos dos fármacos , Baço/imunologia , Baço/microbiologia , Sporothrix/efeitos dos fármacos , Sporothrix/isolamento & purificação , Esporotricose/imunologia , Esporotricose/microbiologia , Esporotricose/patologia , Células Th1/imunologia , Células Th1/microbiologia
10.
J BUON ; 19(4): 895-9, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25536592

RESUMO

PURPOSE: Breast cancer (BC) is the most frequently diagnosed form of cancer and the leading cause of cancer-related deaths among females in the world. RESULTS of several studies showed that the genome of primary cancer patients (naive for any treatment) is unstable. The purpose of the present study was to evaluate the genomic instability in BC patients by means of buccal cells micronucleus (MN) cytome assay Methods: The frequencies of nuclear anomalies including MN, binucleates (BN), broken eggs (BE), condensed chromatin (CC), karyorrhexis (KR) and karyolysis (KL) were evaluated in exfoliated buccal mucosa cells of Mexican women with primary BC and healthy women. Buccal cells were collected from 21 BC patients (9 with stage I and 12 with stage II) and from 20 healthy females used as control group. RESULTS: The results of the evaluation of cells showed that the frequencies of MN, BN, BE, KR and KL were significantly increased in the pooled group of BC patients compared with the control group. However, no one parameter of buccal MN-cytome assay in patients with stage I BC was significant compared with controls and BC patients with stage II. CONCLUSION: Application of the buccal MN-cytome assay for the study of genomic instability in primary BC patients showed that both genotoxic and cytotoxic effects can be evaluated in such patients.


Assuntos
Neoplasias da Mama/genética , Testes para Micronúcleos , Estudos de Casos e Controles , Núcleo Celular , Feminino , Humanos , Mucosa Bucal/citologia
11.
Mutagenesis ; 29(6): 427-31, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25232046

RESUMO

The aim of this study is to assess the frequency of micronucleated cell (MNC) and nuclear abnormalities (NA) in the buccal mucosa cells of females with anorexia nervosa (AN) or bulimia nervosa (BN), compared with healthy women. Individuals with AN and BN have inadequate feeding and compensatory behaviour to avoid weight gain. These behaviours can cause extreme body stress, thereby inducing DNA damage. In a cross-sectional study, we assessed the frequency of MNC and NA in the buccal mucosa cells of female participants with AN or BN. All of these patients had been admitted to a private clinic for the treatment of eating disorders after diagnosis with AN (n = 10) or BN (n = 7) according to the DSM-IV. Age-matched healthy female participants (n = 17) composed the control group. Oral mucosa samples were collected, fixed, stained by aceto-orcein/fast green and microscopically examined. Normal cells, MNC and NAs were counted within a 2000 cell sample. The results were analyzed with the Kruskal-Wallis and Mann-Whitney tests. Differences were observed in the frequency of MNC in healthy females (1.2±0.9) versus that of patients with AN (3.4±1.5) (P < 0.0001) and BN (4.1±2.2) (P < 0.001). No differences were found among these groups in terms of NA. AN and BN are related to the loss of genetic material through chromosomal fractures and/or damage to the mitotic spindle (i.e. possibly a result of a deficiency in DNA precursors). Self-imposed compensatory behaviours in AN and BN, such as severe food restriction, potential malnutrition, vomiting, use of diuretics and laxatives and acute exhaustive exercise, are possible inducers of MNC and genotoxic damage. Of these compensatory behaviours, only vomiting has not been linked to genotoxic damage. This is the first report in women with BN, which should be studied in the future.


Assuntos
Anorexia Nervosa/patologia , Bulimia Nervosa/patologia , Micronúcleos com Defeito Cromossômico , Mucosa Bucal/patologia , Adolescente , Adulto , Antropometria , Estudos de Casos e Controles , Feminino , Humanos , Adulto Jovem
12.
Clin Rev Allergy Immunol ; 47(1): 73-90, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24840362

RESUMO

Posttranslational modifications (PTMs) are defined as covalent modifications occurring in a specific protein amino acid in a time- and signal-dependent manner. Under physiological conditions, proteins are posttranslationally modified to carry out a large number of cellular events from cell signaling to DNA replication. However, an absence, deficiency, or excess in PTMs of a given protein can evolve into a target to trigger autoimmunity, since PTMs arise in the periphery and may not occur in the thymus; hence, proteins with PTMs never tolerize developing thymocytes. Consequently, when PTMs arise during cellular responses, such as inflammation, these modified self-antigens can be taken up and processed by the antigen-presenting cells (APCs). Autoreactive T cells, which recognize peptides presented by APCs, can then infiltrate into host tissue where the modified antigen serves to amplify the autoimmune response, eventually leading to autoimmune pathology. Furthermore, a PTM occurring in an amino acid residue can induce changes in the net charge of the protein, leading to conformational modifications in the tertiary and quaternary structure of the protein, especially interaction with human leukocyte antigen (HLA) molecules. Molecular mimicry (MM) was until now the prevailing hypothesis explaining generation of autoimmunity; nevertheless, experimental animal models need inflammation via infection or other immunogens to ensure autoimmunity; MM alone is not sufficient to develop autoimmunity. PTMs could arise as an additive factor to MM, which is required to start an autoimmune response. PTMs have been found to be present in different pathologic conditions such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), antiphospholipid syndrome, and primary biliary cirrhosis. The aim of the present review is to expose protein posttranslational modifications and the evidence suggesting their role in the generation of autoimmunity.


Assuntos
Autoantígenos/metabolismo , Doenças Autoimunes/imunologia , Autoimunidade , Processamento de Proteína Pós-Traducional , Animais , Apresentação do Antígeno , Autoantígenos/imunologia , Modelos Animais de Doenças , Antígenos HLA/metabolismo , Humanos , Conformação Molecular
13.
Dis Markers ; 2014: 956835, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24778463

RESUMO

The use of biomarkers as tools to evaluate genotoxicity is increasing recently. Methods that have been used previously to evaluate genomic instability are frequently expensive, complicated, and invasive. The micronuclei (MN) and nuclear abnormalities (NA) technique in buccal cells offers a great opportunity to evaluate in a clear and precise way the appearance of genetic damage whether it is present as a consequence of occupational or environmental risk. This technique is reliable, fast, relatively simple, cheap, and minimally invasive and causes no pain. So, it is well accepted by patients; it can also be used to assess the genotoxic effect derived from drug use or as a result of having a chronic disease. Furthermore the beneficial effects derived from changes in life style or taking additional supplements can also be evaluated. In the present paper, we aim to focus on the explanation of MN test and its usefulness as a biomarker; we further give details about procedures to perform and interpret the results of the test and review some factors that could have an influence on the results of the technique.


Assuntos
Dano ao DNA , Micronúcleos com Defeito Cromossômico , Mucosa Bucal/patologia , Animais , Biomarcadores , Núcleo Celular/efeitos dos fármacos , Núcleo Celular/patologia , Núcleo Celular/efeitos da radiação , Citodiagnóstico , Humanos , Testes para Micronúcleos
14.
Int. j. morphol ; 31(2): 650-657, jun. 2013. ilus
Artigo em Espanhol | LILACS | ID: lil-687119

RESUMO

Los micronúcleos son fragmentos o cromosomas completos que quedan fuera del núcleo durante la mitosis; mediante su estudio se pueden evaluar los efectos de genotóxicos ambientales y ocupacionales. Esta prueba es ampliamente utilizada y es una alternativa eficaz, sencilla y económica para detectar la perdida de material genético. Por otra parte, la cavidad oral puede reflejar el estado de salud de los individuos, debido a que la mucosa que la recubre, puede presentar evidencias a nivel microscópico como macroscópico de cambios indicativos de enfermedad local sistémica o por exposición a sustancias tóxicas así como efectos secundarios por tratamientos. Dichas ventajas, favorecen su utilización en pruebas para evaluar genotóxicos o citotóxicos. La mucosa es una barrera protectora del resto del organismo, es un punto de contacto de agentes potencialmente peligrosos; por tanto, se torna susceptible de sufrir daños. El epitelio de revestimiento oral (60 por ciento) es estratificado no queratinizado formado por células con abundante citoplasma, permite la penetración de colorantes y facilita la observación e identificación de características morfológicas del núcleo y membrana celular. Además la mucosa tiene elevada capacidad proliferativa y aunque esta particularidad mantiene la población celular constante, por otro lado, se vuelve más vulnerable a daño al ADN. Esto cobra relevancia ya que el 90 por ciento del cáncer tienen origen epitelial, así que la mucosa oral es usada para monitorear eventos genotóxicos tempranos causados por cancerígenos inhalados o ingeridos. Este epitelio es de fácil acceso, poco invasivo, por lo que al tomar la muestra a los individuos, se les genera mínimo estrés. Por todo lo anterior, el epitelio oral es un tejido ideal para aplicar la técnica de micronúcleos y detección de anormalidades nucleares sin necesidad de cultivos celulares, lo que representa una oportunidad para realizar estudios epidemiológicos en poblaciones de alto riesgo.


Micronucleus are fragments or whole chromosomes that are outside the nucleus during mitosis. Through this study we can evaluate the environmental and occupational the genotoxic effects. This test is widely used because it is a very effective alternative, it is a simple, fast and inexpensive way to detect the loss of genetic material. Meanwhile a healthy oral cavity is evidenced because in the overlying mucosa changes indicative of local or systemic disease, toxic exposure and side effects of treatments can be observed. This favors their use in tests to assess the presence of genotoxins or cytotoxins. Although protective barrier from the rest of the body is the point of contact of potentially dangerous agents thus becoming susceptible to damage. Coating and oral epithelium (60 percent) are formed by stratified non-keratinized cells with abundant cytoplasm, allowing the absorption of dyes and facilitating microscopic observation and identification of nucleus and membrane morphological characteristics. It has a particularly proliferative capacity, and even though this particularity maintains constant cell population, on the other hand, becomes more vulnerable to DNA damage. This information is relevant as 90 percent of all cancers are of epithelial origin. Therefore, the oral mucosa is used to monitor early events caused by inhaled or ingested genotoxic carcinogens. Epithelium is easily accessible and minimally invasive, thereby generating less stress when samples are obtained from study participants. In view of the above, oral epithelium tissue is ideal for implementing micronucleus assay and for the detection of nuclear abnormalities without the need for cell cultures, which presents a unique opportunity for epidemiological studies in high-risk populations.


Assuntos
Humanos , Mucosa Bucal/citologia , Testes para Micronúcleos/métodos , Testes de Mutagenicidade
16.
Mutat Res ; 728(3): 88-97, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21763453

RESUMO

The human buccal micronucleus cytome assay (BMCyt) is one of the most widely used techniques to measure genetic damage in human population studies. Reducing protocol variability, assessing the role of confounders, and estimating a range of reference values are research priorities that will be addressed by the HUMN(XL) collaborative study. The HUMN(XL) project evaluates the impact of host factors, occupation, life-style, disease status, and protocol features on the occurrence of MN in exfoliated buccal cells. In addition, the study will provide a range of reference values for all cytome endpoints. A database of 5424 subjects with buccal MN values obtained from 30 laboratories worldwide was compiled and analyzed to investigate the influence of several conditions affecting MN frequency. Random effects models were mostly used to investigate MN predictors. The estimated spontaneous MN frequency was 0.74‰ (95% CI 0.52-1.05). Only staining among technical features influenced MN frequency, with an abnormal increase for non-DNA-specific stains. No effect of gender was evident, while the trend for age was highly significant (p<0.001). Most occupational exposures and a diagnosis of cancer significantly increased MN and other endpoints frequencies. MN frequency increased in heavy smoking (≥40cig/day, FR=1.37; 95% CI 1.03-.82) and decreased with daily fruit consumption (FR=0.68; 95% CI 0.50-0.91). The results of the HUMN(XL) project identified priorities for validation studies, increased the basic knowledge of the assay, and contributed to the creation of a laboratory network which in perspective may allow the evaluation of disease risk associated with MN frequency.


Assuntos
Testes para Micronúcleos/métodos , Mucosa Bucal/citologia , Fatores Etários , Bochecha , Nível de Saúde , Humanos , Estilo de Vida , Exposição Ocupacional , Padrões de Referência , Fatores Sexuais
17.
Drug Chem Toxicol ; 34(3): 294-9, 2011 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-21649484

RESUMO

Methylphenidate (MPH; Ritalin®; Novartis Pharmaceuticals, Inc., Basel, Switzerland) has been prescribed to treat attention deficit/hyperactivity disorder (ADHD) since its approval by the U.S. Food and Drug Administration over 50 years ago. Due to concerns that MPH might induce cytogenetic alterations in children, treatment with this drug has been a controversial issue. In the present study, we assessed the frequency of micronucleated erythrocytes (MNEs), micronucleated polychromatic erythrocytes (MNPCEs), and polychromatic erythrocytes (PCEs) in peripheral blood samples from mice treated with three different doses of MPH (30, 60, or 125 mg/kg). We found no evidence of increased MNEs or MNPCEs, nor did PCEs decline. These results add to the accumulating evidence that MPH does not induce genotoxic or cytotoxic damage.


Assuntos
Eritrócitos/efeitos dos fármacos , Metilfenidato/toxicidade , Mutagênicos/toxicidade , Administração Oral , Animais , Relação Dose-Resposta a Droga , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Micronúcleos com Defeito Cromossômico/induzido quimicamente , Testes para Micronúcleos
18.
Artigo em Inglês | MEDLINE | ID: mdl-20390845

RESUMO

This study is a follow-up of previous research in which we described the frequency of spontaneous micronucleated erythrocytes (MNE) in the Goodeid Xenotocoa melanosoma collected from Lake La Alberca, located in the state of Michoacan, Mexico. In the present work, we measured micronuclei (MN) and nuclear abnormalities (NA) in erythrocytes of peripheral blood. Bioassays taken at 24 or 96 hours in either the cyclophosfamide (CP) or colchicine (COL) showed a significant increase in MN and BC (P values ranging from 0.0499 to 0.0036) compared with information from wild organisms collected over 3 years. Concentrationdependent and time-dependent responses support the proposal of using endemic Xenotoca melanosoma as a bioindicator of genotoxicity and cytotoxicity with a high transcendence for the health of the entire ecosystem and evaluation of the Lerma-Chapala watershed.


Assuntos
Aneugênicos/toxicidade , Colchicina/toxicidade , Ciclofosfamida/toxicidade , Ciprinodontiformes , Eritroblastos/efeitos dos fármacos , Micronúcleos com Defeito Cromossômico/induzido quimicamente , Mutagênicos/toxicidade , Animais , Núcleo Celular/efeitos dos fármacos , Núcleo Celular/patologia , Relação Dose-Resposta a Droga , Monitoramento Ambiental , Eritroblastos/fisiologia , Feminino , Água Doce , Masculino , México , Testes para Micronúcleos
19.
Artigo em Inglês | MEDLINE | ID: mdl-17680492

RESUMO

A series of bioindicator organisms for aquatic ecosystems are being maintained under laboratory conditions in order to analyze effects of pollution on aquatic wildlife and potential effects on human health. Growth kinetics of algae Pseudokirchneriella subcapitata was used to evaluate effects of the surfactant nonilphenol (NP). Brachionus calyciflorus was used to set up a model of endocrine disruption using the fungicide vinclozolin (Vc). We exposed salamanders from the genus Ambystoma sp., to different concentrations of both the aneugen colchicine (COL) and the clastogen cyclophosphamide (CP) and we determined the frequency of micronucleated cells (MNC) in their shed skin. The presence of spontaneous micronuclei in peripheral blood erythrocytes from 10 fish species in Lake "La Alberca," Michoacan (Mexico), was evaluated as a possible biological indicator of genotoxic agents. Results confirm the sensivity of Pseudokirchneriella subcapitata to growth kinetics: the range of concentration of NP (20, 200 and 2000 microg L(- 1)) shows an inverted U shape in its maximum growth rate; Dimethyl sulfoxide (DMSO) used as a positive control and to solvate NP induced an inverse stimulatory effect on growth rate in the range of concentrations analyzed (0.0023, 0.023 and 0.23% v v(- 1)). In the use of the rotifer Brachionus calyciflorus, the range of Vc from 0.185 mg L(- 1) to 3 mg L(- 1) clearly showed an inverted U shape characteristic of endocrine disruptions. We were able to use shed skin from Ambystoma sp., to measure MNC frequencies induced either by an aneugenic or a clastogenic compound. The MNC frequency was increased significantly by all doses of COL and CP, administered either as single or repeated exposures. The presence of MNC in the shed skin and the speed of sloughing lead us to propose that the sheds of Ambystoma sp., or other amphibians that slough their skin, as suitable alternative models for detecting genotoxic exposures relevant to aquatic environments. In the survey to determine potential biological fish indicators for genotoxic agents, the frequency of spontaneous micronucleated erythrocytes (MNE) found in the goodeid Xenotoca melanosoma (3.7 +/- 1.6 MNC) and the cichlid Oreochromis aureus (2.0 +/- 1.0 MNC) suggests that these species can be considered as potential biological indicators.


Assuntos
Poluentes Químicos da Água/toxicidade , Animais , Clorófitas/efeitos dos fármacos , Clorófitas/crescimento & desenvolvimento , Colchicina/toxicidade , Ciclofosfamida/toxicidade , Feminino , Peixes , Fungicidas Industriais/toxicidade , Dose Letal Mediana , Masculino , México , Testes para Micronúcleos , Mutagênicos/toxicidade , Oxazóis/toxicidade , Fenóis/toxicidade , Reprodução/efeitos dos fármacos , Rotíferos/efeitos dos fármacos , Rotíferos/fisiologia , Pele/citologia , Urodelos/genética
20.
Avian Pathol ; 35(3): 206-10, 2006 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-16753611

RESUMO

Nuclear abnormalities in erythrocytes, as micronuclei and nuclear buds (BE), are considered potential biomarkers of genotoxic exposure. We described previously the frequency of spontaneous micronucleated erythrocytes (MNE) in the species Aratinga canicularis. Here, we have used this species to evaluate the induction of MNE and BE by mitomycin-C. Animals were given a single intracoelomic injection of 0, 2, 3 or 4 mg/kg mitomycin-C on two consecutive days. A drop of blood was obtained after 0, 24, 48 and 72 h, and stained smears were used to count micronucleated polychromatic erythrocytes (MNPCE) and polychromatic erythrocytes with buds (BPCE)/1000 polychromatic erythrocytes. The number of MNE and BE in 10 000 total erythrocytes was also counted. MNPCE and BPCE frequencies were elevated at 24, 48, and 72 h after the administration of the lower dose (P<0.03). At a 3 mg/kg dose, the frequency of MNPCE increased at 48 and 72 h (P<0.04) whereas the number of BPCE increased, but not significantly. Administration of 4 mg/kg mitomycin-C increased the number of MNE observed at 72 h (P<0.03), the number of MNPCE at 48 h (P<0.01) and 72 h (P<0.006), the BE frequency at 72 h (P<0.05), and the frequency of BPCE at 48 and 72 h (P<0.001). While mitomycin-C appears to produce a parallel increase in MNPCE and BPCE frequencies, the MNE seemed to be a more sensitive indicator of genotoxicity than the BE. This suggests that evaluating BE and MNE in routine haematological analysis should be considered to evaluate environmental genotoxic exposure.


Assuntos
Núcleo Celular/efeitos dos fármacos , Núcleo Celular/genética , Dano ao DNA/efeitos dos fármacos , Eritrócitos/efeitos dos fármacos , Eritrócitos/patologia , Mitomicina/toxicidade , Papagaios , Animais , Núcleo Celular/patologia , Relação Dose-Resposta a Droga , Feminino , Masculino , Micronúcleos com Defeito Cromossômico/efeitos dos fármacos , Micronúcleos com Defeito Cromossômico/veterinária , Mutagênicos/toxicidade , Papagaios/sangue , Papagaios/genética
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