RESUMO

This study aimed to evaluate all studies which used the micronucleus assay using oral cells in the attempt to understand whether such technique is efficient in evaluating genotoxicity in gas station attendants. Full manuscripts from 16 studies were carefully selected by the authors. Our results demonstrate that continuous exposure to derivatives of petroleum may lead to genotoxic effects since all studies demonstrated positive findings (16 out of 16) and 11 of them had a strong or moderate final rating. In summary, our results reveal that gas station attendants are occupationally exposed to genotoxic agents and that the micronucleus assay in oral mucosa is indeed an effective method to evaluate genotoxicity in this specific case. Such findings are very important for protecting these professionals who are continuously exposed to chemicals for long periods.

Assuntos

Testes para Micronúcleos , Mucosa Bucal , Exposição Ocupacional , Testes para Micronúcleos/métodos , Humanos , Exposição Ocupacional/efeitos adversos , Mucosa Bucal/efeitos dos fármacos , Mucosa Bucal/citologia , Carcinogênese/induzido quimicamente , Carcinogênese/efeitos dos fármacos , Biomarcadores/análise , Petróleo/toxicidade , Medição de Risco/métodos

RESUMO

BACKGROUND: This pilot study aimed to evaluate the mutagenic effects in cells of the oral mucosa after exposure to two different cone beam computed tomography (CBCT). METHODS: Eighteen adults were submitted to the different CBCT (Carestream CS8100 3D and I-CAT). The cells were collected immediately before the CBCT exposure and 10 days later, when the material was placed on a slide and stained using the Feulgen/Fast Green technique. Microscopic analysis counted micronuclei and other nuclear alterations, which are indicative of cytotoxicity such as pyknosis, karyolysis, karyorrhexis, and binucletion. 2000 cells were analyzed. The statistical analysis was performed with the Wilcoxon Signed-Rank test to compare the frequency of cellular alterations, and the Mann-Whitney U test to compare different CBCTs, both with a significance level of 5%. RESULTS: There was no statistically significant difference in the micronucleated cell count before and after the exposition to the ionizing radiation from I-CAT (p = .298) and CS8100 3D (p = .203) A significate increase of pyknosis (p < .001), karyolysis (p < .001), karyorrhexis (p < .001), and binucletion (p < .001) were noted on I-CAT CBCT. There was no statistically significant difference in cellular alterations in CS8100 3D CBCT. CONCLUSION: Despite the increase in micronuclei after exposure, this study indicates that there is no evidence of genotoxicity. On the other hand, the I-CAT CBCT produced cytotoxic effects.

Assuntos

Mucosa Bucal , Mutagênicos , Adulto , Humanos , Projetos Piloto , Núcleo Celular , Tomografia Computadorizada de Feixe Cônico/efeitos adversos

RESUMO

Abstract The aim of this systematic review was to evaluate published papers regarding the micronucleus assay in oral mucosal cells of patients undergoing orthodontic therapy (OT). A search of the scientific literature was made in the PubMed, Scopus, and Web of Science databases for all data published until November, 2021 using the combination of the following keywords: "fixed orthodontic therapy," "genetic damage", "DNA damage," "genotoxicity", "mutagenicity", "buccal cells", "oral mucosa cells," and "micronucleus assay". The systematic review was designed according to the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines. Nine studies were retrieved. Some authors demonstrated that OT induces cytogenetic damage in oral mucosal cells. Out of the nine studies included, two were classified as strong, five as moderate, and two as weak, according to the quality assessment components of the Effective Public Health Practice Project (EPHPP). Meta-analysis data revealed no relationship between mutagenicity in oral cells and OT in different months of treatment. At one month, the SMD = 0.65 and p = 0.08; after three months of OT, the SMD = 1.21 and p = 0.07; and after six months of OT, the SMD = 0.56 and p = 0.11. In the analyzed months of OT, I2 values were >75%, indicating high heterogeneity. In summary, this review was not able to demonstrate that OT induces genetic damage in oral cells. The study is important for the protection of patients undergoing fixed OT, given that mutagenesis participates in the multi-step process of carcinogenesis.

RESUMO

SUMMARY OBJECTIVE: The objective of this study was to evaluate cytogenetic changes in individuals submitted to oral human immunodeficiency virus pre-exposure prophylaxis use through the micronucleus test in oral mucosa. METHODS: This study consisted of 37 individuals, of whom 17 comprised the pre-exposure prophylaxis group and 20 comprised the control group. A total of 2,000 cells per slide were analyzed for the determination of micronuclei, binucleation, nuclear buds, and cytotoxicity parameters: pyknosis, karyolysis, and karyorrhexis (KR), in a double-blind manner. The repair index was also evaluated in this setting. RESULTS: In the mutagenicity parameters, the pre-exposure prophylaxis group showed increased frequencies of micronuclei (p=0.0001), binucleation (p=0.001), and nuclear buds (p=0.07). Regarding the cytotoxicity parameters, there was an increase with a statistical difference (p≤0.05) in the karyorrhexis frequency (p=0.001). Additionally, the repair system efficiency decreased in the pre-exposure prophylaxis group. CONCLUSION: These results indicate that individuals undergoing pre-exposure prophylaxis use have geno- and cytotoxicity in oral mucosal cells.

RESUMO

SUMMARY OBJECTIVE: The objective of this study was to evaluate possible cytogenetic changes in children and adolescents with human immunodeficiency virus on antiretroviral therapy, through the micronucleus test in oral mucosa. METHODS: This was a prospective study consisted of 40 individuals, of whom 21 comprised the human immunodeficiency virus group and 19 comprised the control group. Children and adolescents with human immunodeficiency virus were enrolled. The inclusion criteria were <18 years old and consent in participating in the study. The exclusion criteria were the presence of numerous systemic comorbidities, oral lesions, the habit of smoking, alcohol consumption, and X-rays or CT scans taken within 15 days prior to sample collection. A gentle scraping was performed on the inner portion of the jugal mucosa on both sides. A total of 2,000 cells per slide were analyzed for the determination of mutagenicity parameters as follows: micronuclei, binucleation, and nuclear buds. For measuring cytotoxicity, the following metanuclear changes were evaluated: pyknosis, karyolysis, and karyorrhexis, in a double-blind manner. The repair index was also evaluated in this setting. RESULTS: The human immunodeficiency virus group showed high frequencies of micronuclei (p=0.05), binucleated cells (p=0.001), and nuclear buds (p=0.03). In the cytotoxicity parameters, represented by the cell death phases, there was an increase with statistical difference (p≤0.05) in the karyorrhexis frequency (p=0.05). Additionally, repair index was decreased in the human immunodeficiency virus group. CONCLUSION: These results indicate that human immunodeficiency virus -infected individuals undergoing antiretroviral therapy have cytogenetic changes in oral mucosal cells.

RESUMO

Aim: This study aimed to investigate whether non-ionizing radiation emitted by smartphones is likely to cause genotoxic effects on oral epithelial cells. Methods: Thirty adults were distributed into two groups according to the mobile phone brand used, namely Samsung (Samsung, Seoul, South Korea) and Apple (Apple, California, USA). The material was collected with gentle swabbing of the right and left buccal mucosa using a cervical brush, then the micronucleus test was performed. Results: The Mann-Whitney test with a 5% significance level did not reveal statistically significant differences in micronuclei frequency between the exposed and non-exposed sides (p=0.251). The different brands do not seem to cause risks of inducing genetic damage because there were no statistically significant differences between them (p=0.47). Conclusion: Therefore, our results suggest no correlations of micronuclei frequency in the exposed buccal cells of mobile phone users at the exposure standard levels observed

Assuntos

Humanos , Masculino , Feminino , Adulto , Radiação não Ionizante/efeitos adversos , Ondas de Rádio , Testes para Micronúcleos , Células Epiteliais , Smartphone , Mucosa Bucal , Testes de Mutagenicidade

RESUMO

INTRODUCTION: The light-emitting diode (Led) in the violet spectrum associated or not with hydrogen peroxide (HP) has been suggested as a promising technique for dental bleaching. Violet led has a wavelength of 405-410 nm, which is very close to that of ultraviolet (UV) radiation, and this has raised biological safety concerns. AIM: To investigate the effectiveness of the violet led dental bleaching technique by evaluating color parameters, enamel surface microhardness, and biological safety analysis. METHODS: One hundred bovine dental blocks were divided into groups according to the bleaching technique (G1 - only HP; G2 - HP associated with blue led; G3 - only blue led; G4 - HP associated with a violet led; and G5 - only violet led). The color analysis (ΔE, ΔL, and WID) and enamel surface microhardness were assessed before and after bleaching (immediately, 5, 14, and 30 days). The biological safety of the violet led irradiation was assessed by measuring the number of micronuclei formed in human cells in culture in response to irradiation. Data analysis included Kruskal-Wallis test, Friedman test, and Mann-Whitney test. RESULTS: In groups G4 and G5 there was the formation of precipitates on the enamel surface. At the time of 14 days, it was observed that the G2 group had lower values of microhardness than G5. ΔL and ΔE showed differences between groups in experimental times. Mean percentages of micronuclei occurrence were similar in the control group and the violet led group. CONCLUSION: The violet led irradiation can be applied for dental bleaching because this approach produces significant color changes preserving tooth enamel integrity and causes no genotoxic effects on vital cells.

Assuntos

Fotoquimioterapia , Clareadores Dentários , Clareamento Dental , Animais , Bovinos , Humanos , Peróxido de Hidrogênio , Fotoquimioterapia/métodos , Clareamento Dental/métodos , Raios Ultravioleta

RESUMO

Abstract Introduction: Chronic rhinosinusitis with nasal polyps, a prevalent disease affecting around 2% of the world population, is characterized by symptomatic inflammation of the nasal mucosa and impairment of quality of life. Chronic rhinosinusitis with nasal polyps has a multifactorial etiology, involving a dysfunctional host response to environmental factors. Thus, inflammatory models may be useful to shed light on the pathophysiology of this disease. Micronucleus count has been used to screen DNA damage in various tissues. Objective: To investigate the association between frequency of micronucleus in exfoliated cells from the nasal cavity of patients with chronic rhinosinusitis with nasal polyps and disease severity. Methods: This cross-sectional study included 21 patients with chronic rhinosinusitis with nasal polyps and 19 controls without disease. None of the participants were smokers. Results: Mean micronucleus count was 3.690 per 1000 cells (±2.165) in individuals with vs. 1.237 per 1000 cells (±0.806) in controls; (Student's t test = 4.653, p< 0.001). Nasal surgery in the past 5 years and aspirin-exacerbated respiratory disease were not associated with nicronucleus count (p= 0.251). Conclusion: Micronucleus count seems to be linked to chronic rhinosinusitis with nasal polyps, providing a new perspective for the evaluation of this disorder.

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Resumo Introdução: A rinossinusite crônica com pólipos nasais, doença prevalente que afeta cerca de 2% da população mundial, é caracterizada por inflamação sintomática da mucosa nasal e comprometimento da qualidade de vida. A rinossinusite crônica com pólipos nasais tem etiologia multifatorial, envolvendo resposta disfuncional do hospedeiro a fatores ambientais. Assim, modelos inflamatórios podem ser úteis para esclarecer a fisiopatologia dessa doença. A contagem de micronúcleos tem sido usada para rastrear danos no DNA em vários tecidos. Objetivo: Investigar a associação entre a frequência de micronúcleos em células esfoliadas da cavidade nasal de pacientes com rinossinusite crônica com pólipos nasais e a gravidade da doença. Método: Estudo transversal que incluiu 21 pacientes com rinossinusite crônica com pólipos nasais e 19 controles sem doença. Nenhum dos participantes era fumante. Resultados: A contagem média de micronúcleos foi de 3,690 por 1.000 células (± 2,165) nos indivíduos doentes e 1,237 por 1.000 células (± 0,806) nos controles (teste t de Student = 4,653; p < 0,001). A cirurgia nasal nos últimos 5 anos e a doença respiratória exacerbada por aspirina não foram associadas à contagem de micronúcleos (p = 0,251). Conclusão: A contagem de micronúcleos parece estar ligada à rinossinusite crônica com pólipos nasais, proporcionando uma nova perspectiva para a avaliação dessa doença.

Assuntos

Humanos , Sinusite/complicações , Rinite/complicações , Pólipos Nasais/complicações , Qualidade de Vida , Doença Crônica , Estudos Transversais , Células Epiteliais

RESUMO

Abstract This research aimed to conduct a systematic review and metanalysis to compare the frequency of cell damage in crack users and nonusers, through Micronucleous (MN) test in buccal mucosa cells. A comprehensive search was carried out on MEDLINE via PubMeb, Web of Science, LILACS and the grey literature without restrictions. It was included case-control studies that report the frequency of micronuclei in the oral mucosa of adult crack users and nonusers. A review protocol was registered with PROSPERO (CRD42018115672), and conducted in accordance with the PRISMA guidelines for the report of this systematic review. Furthermore, study quality was evaluated using an adapted Newcastle-Ottawa Scale for cross-sectional studies.The original search yielded 27 references, after eligibility criteriaonly five articles were included. The number of micronuclei was higher in crack users compared to nonusers. Also, secondary outcomes: binucleated cells, nuclear buds, pyknosis, karyorrhexis and karyolysis had higher prevalence in crack users.Crack use is associated with genotoxic and mutagenic effects because there is a higher frequency of micronuclei in exfoliated cells of crack users. In addition, MN test proved to be a goodbiomarker to assess the mutagenic impact of crack use in oral epithelium.

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Resumen Esta investigación tuvo como objetivo realizar una revisión sistemática y un meta-análisis para comparar la frecuencia de daño celular en usuarios de crack y sin crack, a través de la prueba de micronúcleos (MN) en células de la mucosa bucal. Se realizó una búsqueda exhaustiva en MEDLINE a través de PubMeb, Web of Science, LILACS y la literatura gris sin restricciones. Se incluyeron estudios de casos y controles que informaron la frecuencia de micronúcleos en la mucosa oral de usuarios adultos de crack y sin crack. Se registró un protocolo de revisión con PROSPERO (CRD42018115672), y se realizó de acuerdo con las pautas de PRISMA para el informe de esta revisión sistemática. Además, la calidad del estudio se evaluó mediante una escala Newcastle-Ottawa adaptada para estudios transversales. La búsqueda original arrojó 27 referencias, después de los criterios de elegibilidad se incluyeron un total de cinco artículos. El número de micronúcleos fue mayor en los usuarios de crack en compa ración con los usuarios sin crack. Además, los resultados secundarios de células binucleadas, yemas nucleares, picnosis, cario- rrexis y cariólisis tuvieron una mayor prevalencia en los usuarios de crack. El uso de crack se asocia con efectos genotóxicos y mutagénicos porque hay una mayor frecuencia de micronúcleos en las células exfoliadas de los usuarios de crack. Además, la prueba de MN demostró ser un buen biomarcador para evaluar el impacto mutagénico del uso de crack en el epitelio oral.

Assuntos

Humanos , Adolescente , Adulto , Adulto Jovem , Cocaína Crack , Transtornos Relacionados ao Uso de Cocaína/patologia , Mucosa Bucal/patologia , Testes para Micronúcleos/métodos , Mutagênicos

RESUMO

INTRODUCTION: Chronic rhinosinusitis with nasal polyps, a prevalent disease affecting around 2% of the world population, is characterized by symptomatic inflammation of the nasal mucosa and impairment of quality of life. Chronic rhinosinusitis with nasal polyps has a multifactorial etiology, involving a dysfunctional host response to environmental factors. Thus, inflammatory models may be useful to shed light on the pathophysiology of this disease. Micronucleus count has been used to screen DNA damage in various tissues. OBJECTIVE: To investigate the association between frequency of micronucleus in exfoliated cells from the nasal cavity of patients with chronic rhinosinusitis with nasal polyps and disease severity. METHODS: This cross-sectional study included 21 patients with chronic rhinosinusitis with nasal polyps and 19 controls without disease. None of the participants were smokers. RESULTS: Mean micronucleus count was 3.690 per 1000 cells (±2.165) in individuals with vs. 1.237 per 1000 cells (±0.806) in controls; (Student's t test = 4.653, p < 0.001). Nasal surgery in the past 5 years and aspirin-exacerbated respiratory disease were not associated with nicronucleus count (p = 0.251). CONCLUSION: Micronucleus count seems to be linked to chronic rhinosinusitis with nasal polyps, providing a new perspective for the evaluation of this disorder.

Assuntos

Pólipos Nasais , Rinite , Sinusite , Doença Crônica , Estudos Transversais , Células Epiteliais , Humanos , Pólipos Nasais/complicações , Qualidade de Vida , Rinite/complicações , Sinusite/complicações

RESUMO

ABSTRACT BACKGROUND: Gastric cancer is known as the fourth most common cancer. Current treatments for cancer have damaged the sensitive tissues of the healthy body, and in many cases, cancer will be recurrent. Therefore, need for treatments that are more effective is well felt. Researchers have recently shifted their attention towards antipsychotic dopamine antagonists to treat cancer. The anticancer activities of aripiprazole remain unknown. OBJECTIVE: This study aimed to evaluate the efficacy and safety of aripiprazole on gastric cancer and normal cell lines. METHODS: In this regard, the cytotoxicity and genotoxicity of aripiprazole were investigated in MKN45 and NIH3T3 cell lines by methyl tetrazolium assay and on peripheral blood lymphocytes by micronucleus assay. For this purpose, cells were cultured in 96 wells plate. Stock solutions of aripiprazole and cisplatin were prepared. After cell incubation with different concentrations of aripiprazole (1, 10, 25, 50, 100 and 200 μL), methyl tetrazolium solution was added. For micronucleus assay fresh blood was added to RPMI culture medium 1640 supplemented, and different concentrations of aripiprazole (50, 100 and 200 μL) were added. RESULTS: The finding of present study showed that the IC50 of aripiprazole in the cancer cell line (21.36 μg/mL) was lower than that in the normal cell line (54.17 μg/mL). Moreover, the micronucleus assay showed that the frequency of micronuclei of aripiprazole at concentrations below 200 μM was much less than cisplatin. CONCLUSION: Aripiprazole can be a good cytotoxic compound and good candidate for further studies of cancer therapy.

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RESUMO CONTEXTO: O câncer gástrico é conhecido como o quarto câncer mais comum. Os tratamentos atuais para o câncer danificaram os tecidos sensíveis do corpo saudável e, em muitos casos, o cancro será recorrente. Portanto, a necessidade de tratamentos que são mais eficazes é desejada. Recentemente, os pesquisadores mudaram sua atenção para os antagonistas antipsicóticos da dopamina para tratar o câncer. As atividades anticâncer de aripiprazol permanecem desconhecidas. OBJETIVO: Este estudo objetivou avaliar a eficácia e a segurança do aripiprazol no câncer gástrico e nas linhagens celulares normais. MÉTODOS: A este respeito, a citotoxicidade e a genotoxicidade do aripiprazol foram investigadas em linhas celulares MKN45 e NIH3T3 por ensaio de metil tetrazólio e em linfócitos periféricos de sangue por ensaio de micronúcleos. Para este efeito, as células foram cultivadas em 96 placas. As soluções de estoque de aripiprazol e cisplatina foram preparadas. Após incubação celular com diferentes concentrações de aripiprazol (1, 10, 25, 50, 100 e 200 μL), a solução de metil tetrazólio foi adicionada. Para o ensaio do micronúcleo o sangue fresco foi adicionado ao meio de cultura RPMI 1640 suplementado, e as concentrações diferentes de aripiprazole (50, 100 e 200 μL) foram adicionadas. RESULTADOS: O presente estudo mostrou que o IC50 de aripiprazol na linhagem celular cancerosa (21,36 μg/mL) foi menor do que na linha celular normal (54,17 μg/ mL). Além disso, o ensaio de micronúcleos demonstrou que a frequência de micronúcleos de aripiprazol em concentrações inferiores a 200 μM foi muito inferior à cisplatina. CONCLUSÃO: O aripiprazol pode ser um bom composto citotóxico e bom candidato para estudos adicionais da terapia do câncer.

Assuntos

Humanos , Animais , Camundongos , Linfócitos/efeitos dos fármacos , Aripiprazol/toxicidade , Testes para Micronúcleos/métodos , Células NIH 3T3/efeitos dos fármacos , Testes de Mutagenicidade

RESUMO

Ribavirin is an important component of the treatment for hepatitis C virus (HCV) infection and, in combination with the new direct-acting antiviral (DAA) agents, comprises the major current therapeutic regimens. This study evaluated the cytotoxicity and chromosomal instability induced by ribavirin using the in vitro cytokinesis-block micronucleus cytome (CBMN-Cyt) assay in two cell lines with different expression levels of drug-metabolizing enzymes: human hepatocellular carcinoma cells (HepG2) and Chinese hamster ovary (CHO-K1) cells. HepG2 cells were treated with nine concentrations (from 15.3 µg/ml to 3.9 mg/ml) and CHO-K1 cells were exposed to eight concentrations (from 15.3 µg/ml to 1.9 mg/ml) of ribavirin for 24 h. Ribavirin inhibited cell proliferation in both cell lines, but at different concentrations: 3.9 mg/ml in HepG2 and 244.2 µg/ml in CHO-K1 cells. No significant differences were observed regarding aspects of cell death in HepG2 and CHO-K1 cells, reflecting the absence of cytotoxic effects associated to ribavirin. Ribavirin did not increase the frequency of nucleoplasmic bridges (NPBs) and nuclear bud (NBUD). However, when compared to the negative control, a significant increase in micronuclei (MNi) frequency was observed in both cell lines. However, chromosomal instability was induced by higher concentrations of ribavirin in HepG2 cells (from 61.1 to 976.8 µg/ml), compared with CHO-K1 cells (15.3 and 30.5 µg/ml). These results demonstrate the potential of ribavirin to promote chromosomal instability, and suggest that cells with different expressions of drug-metabolizing enzymes show different susceptibility to ribavirin effects.

Assuntos

Antivirais/toxicidade , Proliferação de Células/efeitos dos fármacos , Instabilidade Cromossômica/efeitos dos fármacos , Citocinese/efeitos dos fármacos , Micronúcleos com Defeito Cromossômico/induzido quimicamente , Ribavirina/toxicidade , Animais , Antivirais/metabolismo , Apoptose/efeitos dos fármacos , Células CHO , Cricetulus , Relação Dose-Resposta a Droga , Células Hep G2 , Humanos , Inativação Metabólica , Testes para Micronúcleos , Ribavirina/metabolismo

RESUMO

ABSTRACT Objective To evaluate the induction of DNA damage in peripheral blood mononuclear cells of patients with sickle cell disease, SS and SC genotypes, treated with hydroxyurea. Methods The study subjects were divided into two groups: one group of 22 patients with sickle cell disease, SS and SC genotypes, treated with hydroxyurea, and a Control Group composed of 24 patients with sickle cell disease who were not treated with hydroxyurea. Peripheral blood samples were submitted to peripheral blood mononuclear cell isolation to assess genotoxicity by the cytokinesis-block micronucleus cytome assay, in which DNA damage biomarkers - micronuclei, nucleoplasmic bridges and nuclear buds - were counted. Results Patients with sickle cell disease treated with hydroxyurea had a mean age of 25.4 years, whereas patients with sickle cell disease not treated with hydroxyurea had a mean age of 17.6 years. The mean dose of hydroxyurea used by the patients was 12.8mg/kg/day, for a mean period of 44 months. The mean micronucleus frequency per 1,000 cells of 8.591±1.568 was observed in the Hydroxyurea Group and 10.040±1.003 in the Control Group. The mean frequency of nucleoplasmic bridges per 1,000 cells and nuclear buds per 1,000 cells for the hydroxyurea and Control Groups were 0.4545±0.1707 versus 0.5833±0.2078, and 0.8182±0.2430 versus 0.9583±0.1853, respectively. There was no statistically significant difference between groups. Conclusion In the study population, patients with sickle cell disease treated with the standard dose of hydroxyurea treatment did not show evidence of DNA damage induction.

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RESUMO Objetivo Avaliar o efeito da indução de danos ao DNA em células monocelulares do sangue periférico de pacientes com doença falciforme, genótipos SS e SC, tratados com hidroxiureia. Métodos Os sujeitos da pesquisa foram divididos em dois grupos: um de 22 pacientes com doença falciforme genótipos SS e SC tratados com hidroxiureia, e o outro controle, composto por 24 pacientes com doença falciforme que não eram tratados com o fármaco. As amostras de sangue periférico foram submetidas ao isolamento de células mononucleares do sangue periférico para avaliação da genotoxicidade pelo ensaio de micronúcleo citoma com bloqueio da citocinese, tendo sido quantificados os biomarcadores de danos ao DNA - micronúcleos, pontes nucleoplasmáticas e brotamento nuclear. Resultados Os pacientes com doença falciforme tratados com hidroxiureia apresentaram média de idade de 25,4 anos, enquanto aqueles com doença falciforme não tratados com hidroxiureia tiveram média de idade de 17,6 anos. A dose média de hidroxiureia utilizada pelos pacientes foi de 12,8mg/kg/dia, por período médio de 44 meses. A frequência média de micronúcleos por 1.000 células de 8,591±1,568 foi observada no Grupo Hidroxiureia e de 10,040±1,003 no Grupo Controle. Adicionalmente, a frequência média de pontes nucleoplasmáticas por 1.000 células e brotamento nuclear por 1.000 células para o Grupo Hidroxiureia e Controle foi de 0,4545±0,1707 versus 0,5833±0,2078, e de 0,8182±0,2430 versus 0,9583±0,1853, respectivamente. Não houve diferença estatisticamente significativa entre os grupos. Conclusão Na população estudada de pacientes com doença falciforme com tratamento em dose padrão de hidroxiureia, não houve evidência de indução de danos ao DNA.

Assuntos

Humanos , Masculino , Feminino , Pré-Escolar , Criança , Adolescente , Adulto , Adulto Jovem , Dano ao DNA/efeitos dos fármacos , Inibidores da Síntese de Ácido Nucleico/farmacologia , Hidroxiureia/farmacologia , Anemia Falciforme/genética , Dano ao DNA/genética , Testes para Micronúcleos , Inibidores da Síntese de Ácido Nucleico/efeitos adversos , Inibidores da Síntese de Ácido Nucleico/uso terapêutico , Citocinese , Hidroxiureia/efeitos adversos , Hidroxiureia/uso terapêutico , Anemia Falciforme/tratamento farmacológico , Pessoa de Meia-Idade , Testes de Mutagenicidade , Mutação/efeitos dos fármacos

RESUMO

Introduction: The quantification of chromosomal instability is an important parameter to assess genotoxicity and radiosensitivity. Most conventional techniques require cell cultures or laborious microscopic analyses of chromosomes or nuclei. However, a flow cytometry that selects the reticulocytes has been developed as an alternative for in vivo studies, which expedites the analytical procedures and increases up to 20 times the number of target cells to be analyzed. Objectives: To standardize the flow cytometry parameters for selecting and quantifying the micronucleated reticulocytesCD71+ (MN-RET) from freshly drawn peripheral blood and to quantify the frequency of this abnormal cell subpopulation as a measure of cytogenetic instability in populations of healthy volunteers (n =25), and patients (n=25), recently diagnosed with high-grade gliomas before the onset of treatment. Materials and methods: Blood cells were methanol-fixed and labeled with anti-CD-71-PE for reticulocytes, antiCD-61-FITC for platelet exclusion, and propidium iodide for DNA detection in reticulocytes. The MN-RETCD71+ cell fraction was selected and quantified with an automatic flow cytometer. Results: The standardization of cytometry parameters was described in detail, emphasizing the selection and quantification of the MN-RETCD71+ cellular fraction. The micronuclei basal level was established in healthy controls. In patients, a 5.2-fold increase before the onset of treatment was observed (p <0.05). Conclusion: The data showed the usefulness of flow cytometry coupled with anti-CD-71-PE and anti-CD-61-FITC labeling in circulating reticulocytes as an efficient and high resolution method to quantify chromosome instability in vivo. Finally, possible reasons for the higher average of micronuclei in RETCD71+ cells from untreated high-grade glioma patients were discussed.

Assuntos

Instabilidade Cromossômica , Citometria de Fluxo/métodos , Glioblastoma/genética , Micronúcleos com Defeito Cromossômico , Reticulócitos/patologia , Separação Celular/métodos , Feminino , Glioblastoma/sangue , Glioblastoma/patologia , Humanos , Masculino , Gradação de Tumores , Fatores de Risco , Manejo de Espécimes/métodos

RESUMO

Objetivo. Evaluar la asociación entre el recuento de micronúcleos en células de epitelio bucal y tabaquismo en estudiantes de pregrado de una universidad privada en Ica. Materiales y métodos. Estudio transversal realizado en estudiantes de quienes se obtuvieron células de epitelio bucal y las cuales fueron teñidas con Giemsa para realizar el conteo de micronúcleos en 2000 células por cada muestra, utilizando microscopia de luz visible a un aumento de 100 X. El tabaquismo se valoró por auto reporte y en escala nominal dicotómica (si o no), recolectándose datos sobre la frecuencia y tiempo de consumo de cigarrillos. Resultados. Se evaluaron 129 estudiantes, en los que el 58.1% fueron mujeres y un promedio de edad de 24.9 ± 5.4 años. El 25.6% eran fumadores activos, cuyo recuento promedio de micronúcleos fue de 3.9 ± 2.4, mientras que en los no fumadores de 0.5 ± 1.2. Se encontró una relación directamente proporcional entre presentar tabaquismo y el recuento de micronúcleos (p<0.001). La edad, sexo, número de cigarrillos consumidos y tiempo como fumador no generaron diferencias significativas en el recuento de micronúcleos. Se observó que los estudiantes con tabaquismo presentaron 9.7 veces el riesgo (IC 95%: 4.4 - 21.6) de tener más de 2 micronúcleos/2000 células, ajustado por edad y sexo. Conclusión. El tabaquismo está asociado al recuento de micronúcleos en células de epitelio bucal de estudiantes de una universidad privada en Ica, Perú.

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Objective. To assess the relationship between micronuclei count in buccal epithelium cells and tobacco use in students from a private college in Ica. Materials and Methods. This is a cross-sectional study that was performed in college students. Samples from their buccal epithelium were obtained, and they were stained with Giemsa aiming to perform micronuclei count in 2000 cells per sample, using light microscopy at 100 X. Tobacco use was obtained by self-reporting and using a nominal dichotomic scale (yes/no), and data were collected with respect to frequency and time consuming cigarettes. Results: One hundred and twenty nine students participated, 58.1% were female and their average age was 24.9 ± 5.4 years. One quarter of all participants (25.6%) were active smokers, and their average micronuclei count was 3.9 ± 2.4, while the count in non-smokers was 0.5 ± 1.2. A directly proportional relationship was found between tobacco use and micronuclei count (p<0.001). Age, sex, number of cigarettes per day and time being a smoker did not generate significant differences in micronuclei counts. It was found that students with marked tobacco use had a 9.7 times (95% CI: 4.4-21.6) higher risk for having more than 2 micronuclei/2000 cells, being this adjusted for age and sex. Conclusion. Tobacco use is associated to micronuclei count in buccal epithelial cells from students in a private college in Ica.

RESUMO

Resumen Introducción. La cuantificación de la inestabilidad cromosómica es un parámetro importante para evaluar la genotoxicidad y la radiosensibilidad. Las técnicas convencionales requieren cultivos celulares o laboriosos análisis microscópicos de cromosomas o núcleos. La citometría de flujo en reticulocitos ha surgido como una alternativa para los estudios in vivo, ya que reduce los tiempos de análisis e incrementa hasta en 20 veces el número de células analizables. Objetivos. Estandarizar los parámetros de citometría de flujo requeridos para seleccionar y cuantificar reticulocitos micronucleados (RET-MN) a partir de muestras de sangre periférica, y cuantificar la frecuencia de esta subpoblación anormal como medida de inestabilidad citogenética en sendas poblaciones de voluntarios sanos (n=25) y pacientes (n=25) recién diagnosticados con gliomas de alto grado antes de iniciar el tratamiento. Materiales y métodos. Las células sanguíneas se marcaron con anti-CD71-PE para reticulocitos, anti- CD61-FITC para la exclusión de plaquetas y yoduro de propidio para detectar el ADN en reticulocitos. La fracción celular MN-RETCD71+ se seleccionó y se cuantificó con un citómetro de flujo automático. Resultados. Se describió detalladamente la estandarización de los parámetros citométricos, con énfasis en la selección y la cuantificación de la subpoblación celular MN-RETCD71+. Se establecieron los niveles basales de MN-RETCD71+ en la población de control y en los pacientes se encontró un incremento de 5,2 veces antes de iniciar el tratamiento (p<0,05). Conclusión. Los resultados evidenciaron la utilidad de la citometría de flujo acoplada a la marcación de las células RETCD71+ como método eficiente para cuantificar la inestabilidad cromosómica in vivo. Se sugieren posibles razones del incremento de micronúcleos en células RETCD71+ de pacientes con gliomas.

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Abstract Introduction: The quantification of chromosomal instability is an important parameter to assess genotoxicity and radiosensitivity. Most conventional techniques require cell cultures or laborious microscopic analyses of chromosomes or nuclei. However, a flow cytometry that selects the reticulocytes has been developed as an alternative for in vivo studies, which expedites the analytical procedures and increases up to 20 times the number of target cells to be analyzed. Objectives: To standardize the flow cytometry parameters for selecting and quantifying the micronucleated reticulocytesCD71+ (MN-RET) from freshly drawn peripheral blood and to quantify the frequency of this abnormal cell subpopulation as a measure of cytogenetic instability in populations of healthy volunteers (n =25), and patients (n=25), recently diagnosed with high-grade gliomas before the onset of treatment. Materials and methods: Blood cells were methanol-fixed and labeled with anti-CD-71-PE for reticulocytes, antiCD-61-FITC for platelet exclusion, and propidium iodide for DNA detection in reticulocytes. The MN-RETCD71+ cell fraction was selected and quantified with an automatic flow cytometer. Results: The standardization of cytometry parameters was described in detail, emphasizing the selection and quantification of the MN-RETCD71+ cellular fraction. The micronuclei basal level was established in healthy controls. In patients, a 5.2-fold increase before the onset of treatment was observed (p <0.05). Conclusion: The data showed the usefulness of flow cytometry coupled with anti-CD-71-PE and anti- CD-61-FITC labeling in circulating reticulocytes as an efficient and high resolution method to quantify chromosome instability in vivo. Finally, possible reasons for the higher average of micronuclei in RETCD71+ cells from untreated high-grade glioma patients were discussed.

Assuntos

Feminino , Humanos , Masculino , Reticulócitos/patologia , Glioblastoma/genética , Instabilidade Cromossômica , Micronúcleos com Defeito Cromossômico , Citometria de Fluxo/métodos , Manejo de Espécimes/métodos , Separação Celular/métodos , Fatores de Risco , Glioblastoma/sangue , Glioblastoma/patologia , Gradação de Tumores

RESUMO

OBJECTIVES: A systematic review of clinical studies to evaluate the frequency of micronuclei in the oral mucosa of smokers and non-smokers in adult patients was performed. MATERIALS AND METHODS: A comprehensive search was carried out on MEDLINE via PubMeb, Scopus, Web of Science, LILACS, BBO, and Cochrane Library and SIGLE without restrictions. Dissertations and thesis were searched using the ProQuest Dissertations and Periodicos Capes Thesis Databases. We included only cross-sectional clinical trials that compared the frequency of micronuclei in the oral mucosa of smokers and non-smokers in adult patients. DATA: After the removal of duplicates, 1338 articles were identified. After title and abstract screening, 35 studies remained. Eighteen studies were further excluded, whereas 17 studies remained for qualitative analysis and 16 for the meta-analysis of the primary and secondary outcomes. A significant difference in the frequency of micronuclei in smokers when compared to non-smokers was observed in the present study. CONCLUSIONS: Despite the high variation in the methodology of the assessed studies, this study showed a higher frequency of micronuclei in exfoliated cells of smokers compared to non-smokers. CLINICAL SIGNIFICANCE: The use of tobacco is associated with cytotoxic and genotoxic effects because a higher frequency of micronuclei in exfoliated cells of smokers was observed.

Assuntos

Testes para Micronúcleos , Mucosa Bucal/patologia , Fumar/patologia , Humanos , Mucosa Bucal/citologia

RESUMO

Resumo Objetivo Obter o óleo do Astrocaryum aculeatum (A.a) e avaliar a genotoxidade/antigenotoxidade pelo teste do micronúcleo em células do sangue periférico. Métodos O óleo da A.a foi obtido por prensagem hidráulica. Os animais foram camundongos Swiss, machos e saudáveis com 6-7 semanas de idade, 6 por grupo. Teste genotóxico e antigenotóxico as concentrações foram de 500, 1.000 e 2.000 mg/kg por 0,5 mL (via oral), seguidas ou não de injeção intraperitoneal de doxorrubicina (0,3mL - 15 mg/kg por peso corporal), além do grupo negativo (água) e dimetilsufóxido (600 µL). As amostras de sangue periférico foram coletadas 24h e 48h após o tratamento. Resultados Houve redução estatisticamente significativa na frequência de micronúcleos em células policromáticas que variou de 34,72% à 38,19% para os tratamentos de 24h, e de 63,70 à 66,12% para os de 48h. Conclusão O óleo fixo do tucumã apresentou potencial antigenotóxico para as concentrações em tratamentos agudos.

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Abstract Objective To obtain the oil of Astrocaryum aculeatum (A.a), and evaluate its genotoxicity/antigenotoxicity activities using the micronucleus test in peripheral blood cells. Methods The oil of Astrocaryum aculeatum was obtained by hydraulic pressing. The animals used were healthy Swiss male mice, at 6-7 weeks of age; there were six per group. The genotoxic and antigenotoxic activity of concentrations were 500, 1,000 and 2,000 mg/kg per 0.5 mL (oral), followed or not followed by intraperitoneal injection of doxorubicin (0.3 mL-15 mg/kg by body weight), in addition to a negative group (water) and dimethyl sulfoxide (600 μL). Peripheral blood samples were collected 24h and 48h after treatment. Results A statistically significant reduction was identified in the frequency of micronuclei in polychromatic cells ranging from 34.72% to 38.19% for 24-hour treatments, and from 63.70% to 66.12% for 48 hour. Conclusion The fixed oil of tucumã presented antigenotoxic potential for the concentrations used in acute treatments.

Assuntos

Animais , Masculino , Camundongos , Óleos de Plantas/toxicidade , Leucócitos Mononucleares/efeitos dos fármacos , Extratos Vegetais/análise , Testes para Micronúcleos , Doxorrubicina/toxicidade , Arecaceae/efeitos adversos , Antibióticos Antineoplásicos/toxicidade , Solventes/administração & dosagem , Água Destilada , Dimetil Sulfóxido/administração & dosagem

RESUMO

BACKGROUND AND OBJECTIVE: Previous studies regarding the effects of some local anaesthetics have suggested that these agents can cause genetic damage. However, they have not been tested for genotoxicity related to repetitive administration. The aim of this study was to evaluate the genotoxic potential of local anaesthetics upon repetitive administration. METHODS: 80 male Wistar rats were divided into: group A - 16 rats intraperitoneally injected with lidocaine hydrochloride 2%; group B - 16 rats IP injected with mepivacaine 2%; group C - 16 rats intraperitoneally injected with articaine 4%; group D - 16 rats IP injected with prilocaine 3% (6.0 mg/kg); group E - 8 rats subcutaneously injected with a single dose of cyclophosphamide; and group F - 8 rats intraperitoneally injected with saline. Eight rats from groups A to D received a single dose of anaesthetic on Day 1 of the experiment; the remaining rats were dosed once a day for 5 days. RESULTS: The median number of micronuclei in the local anaesthetics groups exposed for 1 or 5 days ranged from 0.00 to 1.00, in the cyclophosphamide-exposed group was 10.00, and the negative control group for 1 and 5 days was 1.00 and 0.00, respectively (p < 0.0001). A significant difference in the number of micronuclei was observed between the cyclophosphamide group and all local anaesthetic groups (p = 0.0001), but not between the negative control group and the local anaesthetic groups (p > 0.05). CONCLUSION: No genotoxicity effect was observed upon repetitive exposure to any of the local anaesthetics evaluated. .

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JUSTIFICATIVA E OBJETIVOS: Estudos anteriores sobre os efeitos de alguns anestésicos locais sugeriram que esses agentes podem causar alterações genéticas. No entanto, esses agentes não são testados para genotoxicidade relacionada à administração repetida. O objetivo deste estudo foi avaliar o potencial genotóxico de anestésicos locais após repetidas administrações. MÉTODOS: 80 ratos Wistar machos foram alocados em: grupo A - 16 ratos receberam injeção por via intraperitoneal (IP) de cloridrato de lidocaína a 2%; grupo B - 16 ratos receberam injeção IP com mepivacaína a 2%; grupo C - 16 ratos receberam injeção IP de articaína a 4%; grupo D - 16 ratos receberam injeção IP de prilocaína a 3% (6 mg kg-1); grupo E - oito ratos receberam injeção subcutânea em dose única de ciclofosfamida; grupo F - oito ratos receberam injeção IP com solução salina. Oito ratos dos grupos de A a D receberam uma dose única de anestésico no Dia 1 da experiência; os ratos restantes foram dosados uma vez por dia durante cinco dias. RESULTADOS: A mediana do número de micronúcleos nos grupos com anestésicos locais expostos por um ou cinco dias variou de 0 a 1; no grupo exposto à ciclofosfamida foi de 10 e no grupo controle negativo no primeiro e quinto dias foi de 1 e 0, respectivamente (p < 0,0001). Uma diferença significativa foi observada no número de micronúcleos entre o grupo ciclofosfamida e todos os grupos com anestésicos locais (p = 0,0001), mas não entre o grupo controle negativo e os grupos com anestésicos locais (p > 0,05). CONCLUSÃO: Nenhum efeito de genotoxicidade foi observado após a exposição repetida a qualquer um dos anestésicos locais avaliados. .

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JUSTIFICACIÓN Y OBJETIVOS: Estudios previos sobre los efectos de algunos anestésicos locales han mostrado que esos agentes pueden causar alteraciones genéticas. Sin embargo, esos agentes no son testados para la genotoxicidad relacionada con la administración repetida. El objetivo de este estudio fue evaluar el potencial genotóxico de anestésicos locales después de repetidas administraciones. MÉTODOS: 80 ratones Wistar machos se dividieron en: grupo A: 16 ratones que recibieron inyección por vía intraperitoneal (IP) de clorhidrato de lidocaína al 2%; grupo B: 16 ratones a los que se les administró inyección IP con mepivacaína al 2%; grupo C: 16 ratones que recibieron inyección IP de articaína al 4%; grupo D: 16 ratones a los que se les administró inyección IP de prilocaína al 3% (6 mg/kg); grupo E: 8 ratones que recibieron inyección subcutánea en dosis única de ciclofosfamida; grupo F: 8 ratones que recibieron inyección IP con solución salina. Ocho ratones de los grupos A a D recibieron una dosis única de anestésico el primer día de la experiencia; los ratones restantes se dosificaron una vez por día durante 5 días. RESULTADOS: La mediana del número de micronúcleos en los grupos con anestésicos locales expuestos durante uno o 5 días varió de 0 a 1; en el grupo expuesto a la ciclofosfamida fue de 10 y en el grupo control negativo en el primero y quinto día fue de 1 y 0 respectivamente (p < 0,0001). Se observó una diferencia significativa en el número de micronúcleos entre el grupo ciclofosfamida y todos los grupos con anestésicos locales (p = 0,0001), pero no entre el grupo control negativo y los grupos con anestésicos locales (p > 0,05). CONCLUSIÓN: Ningún efecto de genotoxicidad fue observado después de la exposición repetida a cualquiera de los anestésicos locales evaluados. .

Assuntos

Animais , Ratos , Genotoxicidade , Anestésicos Locais/toxicidade , Prilocaína/administração & dosagem , Testes para Micronúcleos/instrumentação , Ratos Wistar , Testes de Mutagenicidade/instrumentação

RESUMO

BACKGROUND AND OBJECTIVE: Previous studies regarding the effects of some local anaesthetics have suggested that these agents can cause genetic damage. However, they have not been tested for genotoxicity related to repetitive administration. The aim of this study was to evaluate the genotoxic potential of local anaesthetics upon repetitive administration. METHODS: 80 male Wistar rats were divided into: group A - 16 rats intraperitoneally injected with lidocaine hydrochloride 2%; group B - 16 rats IP injected with mepivacaine 2%; group C - 16 rats intraperitoneally injected with articaine 4%; group D - 16 rats IP injected with prilocaine 3% (6.0mg/kg); group E - 8 rats subcutaneously injected with a single dose of cyclophosphamide; and group F - 8 rats intraperitoneally injected with saline. Eight rats from groups A to D received a single dose of anaesthetic on Day 1 of the experiment; the remaining rats were dosed once a day for 5 days. RESULTS: The median number of micronuclei in the local anaesthetics groups exposed for 1 or 5 days ranged from 0.00 to 1.00, in the cyclophosphamide-exposed group was 10.00, and the negative control group for 1 and 5 days was 1.00 and 0.00, respectively (p<0.0001). A significant difference in the number of micronuclei was observed between the cyclophosphamide group and all local anaesthetic groups (p=0.0001), but not between the negative control group and the local anaesthetic groups (p>0.05). CONCLUSION: No genotoxicity effect was observed upon repetitive exposure to any of the local anaesthetics evaluated.