Is micronucleus assay in oral cells suitable biomarker for evaluating the risk of carcinogenesis in gas station attendants? A systematic review.

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.

The effect of granulocyte colony stimulating factor on genotoxicity in allogeneic peripheral blood stem cell transplantation donors: a prospective case-control study.

BACKGROUND: Every year, thousands of donors are exposed to granulocyte-colony stimulating factor (G-CSF) for stem cell mobilization in hematopoietic stem cell transplantations (HSCT). Previous studies about the genotoxicity of G-CSF were inconclusive. In this study, the genotoxic effects of G-CSF in peripheral blood stem cell (PBSC) donors were evaluated prospectively by using three different validated and reliable methods for the first time in the literature to the best of our knowledge. METHODS: Donors of PBSC transplantation (n=36), who received G-CSF were evaluated for genotoxicity by micronucleus test (MNT), nuclear division index (NDI), and comet assay (CA). Genotoxic effects are expected to cause an increase in MNT and CA values and decrease in NDI. Blood samples were collected at three timepoints (TP): before starting G-CSF (TP1), after G-CSF for five days (TP2), and one month after the last dose (TP3). Sixteen controls were included for baseline comparison of genotoxicity tests. CD34 cell counts and hemograms were also analyzed. RESULTS: MNT and CA parameters; comet and tail length, tail DNA%, and tail moment, showed no change in time whereas another CA parameter, Olive`s tail moment (OTM) was increased significantly at TP3 compared to both baseline and TP2 (p=0.002 and p=0.017, respectively). Nuclear division index decreased significantly at TP2 (p < 0.001), then increased above baseline at TP3 (p=0.004). Baseline comparison with controls showed higher MN frequency in donors without statistical significance (p=0.059). Whereas, CA results were significantly higher in controls. CD34 cell count showed moderate positive correlation with white blood cell count at TP2 (Pearson R=0.495, p=0.004). CONCLUSIONS: Our results showed the genotoxic effect of G-CSF in healthy donors, in two of the three tests performed, short-term effect in NDI, and long-lasting effect in OTM. So, this study provides novel information for the debate about the genotoxicity of G-CSF and supports the need for further studies with a larger sample size and longer follow-up.

Assessment of Cytotoxic and Genotoxic Effect of Modern Dental Materials in vivo.

Objectives: The aim of the study was to assess the biocompatibility of modern composite and amalgam dental fillings. Material and Methods: The research was conducted on 150 healthy patients between the ages of 10 and 20 who had amalgam and composite fillings between 6 and 12 months. Under in vivo conditions, a swab of buccal cells near the fillings was taken, and the cytotoxic and genotoxic impact of composite and amalgam fillings on these cells was analyzed using the extended micronucleus test (cytomeassay). Results: The results showed statistically significant differences between the groups of subjects with amalgam and composite fillings and subjects without fillings for the following parameters: number of micronuclei (p=0.006), number of buds (p<0.001), number of binuclear cells (p<0.001), number of nucleoplasmic bridges (p<0.001).The number of micronuclei was statistically significantly higher in the group of subjects with amalgam and composite fillings compared to the group without fillings. The results for nuclear buds, for the number of binuclear cells and the number of nucleoplasmic bridges showed that the group with amalgam fillings had a statistically significantly higher number of these changes compared to other groups.The results of the analysis of the relationship between the parameters of the micronucleus test and the number of amalgam and composite surfaces did not show statistically significant values. Parameters indicating cell cytotoxicity were not statistically significantly elevated in subjects with fillings. The results of the analysis of the influence of the patients' lifestyle on the results of the micronucleus test showed statistically significant results for certain predictors (diagnostic X-ray radiation, coffee consumption, consumption of cooked, dried meat and baked food). Conclusion: Based on the results, it can be concluded that the buccal cells of subjects with amalgam fillings showed the highest degree of genotoxic changes, followed by those with composite fillings and the least buccal cells of patients without fillings.

Comparative evaluation of mutagenic effects of two cone-beam computed tomography in oral mucosa cells.

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.

Assessment of the Genotoxic and Cytotoxic Effects of Turpentine in Painters.

Turpentine is a fluid used mainly as a solvent for thinning oil-based paints, obtained by distilling the resin of coniferous trees. Fine art painters use turpentine on a daily basis. The aim of this study was to investigate the genotoxic effect of turpentine and to determine the lymphocyte proliferation index in the peripheral blood of individuals occupationally exposed to turpentine. For this purpose, the cytokinesis-block micronucleus assay (CBMN) was used to determine the total number of micronuclei (MNi), nucleoplasmic bridges (NPB), and nuclear buds (NBUD), as well as the cell proliferation index (CBPI) in the peripheral blood lymphocytes of the subjects. Twenty-two subjects exposed to turpentine daily through their work participated in the study and were compared to twenty subjects in the control group. The results showed a significant increase in the number of micronuclei and other genotoxicity parameters, as well as significant cytotoxicity based on CBPI values. In addition, the genotoxic and cytotoxic effects of turpentine were found to be time-dependent, i.e., the deleterious effects of turpentine on genetic material increase with prolonged exposure. These results strongly suggest that exposure to turpentine vapors may affect genome stability and that occupational safety measures should be taken when using turpentine.

Genotoxic and genoprotective effects of phytoestrogens: a systematic review.

Phytoestrogens are xenoestrogens found in plants with a myriad of health benefits. However, various studies reported the genotoxic effects of these substances. Thus, we reviewed in vitro and in vivo studies published in PubMed, Scopus, and Web of Science to evaluate the genotoxic and the genoprotective potential of phytoestrogens. Only studies written in English and intended to study commercially available phytoestrogens were included. The screening was performed manually. Moreover, the underlying mechanism of action of phytoestrogens was described. Around half of those studies (43%) reported genoprotective results. However, several studies revealed positive results for genotoxicity with specific model organisms and with dose/concentration dependence. The assessment of the selected articles showed substantial differences in the used concentrations and a biphasic response was recorded in some phytoestrogens. As far as we know, this is the first study to assess the genotoxic and genoprotective effects of phytoestrogens systematically.

Cytogenetic changes in oral mucosal cells of human immunodeficiency virus-infected children and adolescents undergoing antiretroviral treatment

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.

The use of micronucleus assay in exfoliated oral cells in patients undergoing fixed orthodontic therapy: a systematic review with meta-analysis

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.

Cytogenetic changes in oral mucosa cells from individuals submitted to oral human immunodeficiency virus pre-exposure prophylaxis use

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.

Mutagenicity in oral cells of individuals exposed to radiofrequency generated by different smartphones

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

Clinical Prospective Assessment of Genotoxic Effects of Dental Implants in Gingival Epithelial Cells.

Objectives: Although titanium-based implants are considered bioinert, it has been found that they are subject to corrosion and wear. This study aimed to evaluate the cytotoxic and genotoxic potential of two implant systems in gingival epithelial cells. Material and methods: Gingival swabs were taken three times from 91 subjects. The first swab was taken before dental implant placement, the second swab 90 days after dental implant placement and the third swab 21 days following the healing abutment placement. DNA damage was analyzed using the micronucleus test. Tested dental implants with corresponding healing abutments were Ankylos and Dentium SuperLine. Results: Of all scored forms of cytogenetic damage in gingival cells of individuals after implementation of tested dental implant systems, only an increase in the number of binucleated cells (P ≤ 0.001) was significant in contrast to control values for both tested implant systems, 90 days after dental implant placement and 21 days following the healing abutment placement. Conclusion: It may be concluded that there are no titanium-based implant dependent cytogenetic damage in gingival epithelial cells. A slight increase in cytogenetic damage has been observed but it is of no biological relevance and might be associated with healing abutment induced effect.

Changes in Radiosensitivity to Gamma-Rays of Lymphocytes from Hyperthyroid Patients Treated with I-131.

This study investigated the peripheral blood lymphocytes (PBL) response to a dose of γ-rays in patients treated with radioiodine (I-131) for hyperthyroidism vs. healthy controls, to gain information about the individual lymphocytes' radio-sensitivity. Blood samples were taken from 18 patients and 10 healthy donors. Phosphorylated histone variant H2AX (γ-H2AX) and micronuclei (MN) induction were used to determine the change in PBL radio-sensitivity and the correlations between the two types of damage. The two assays showed large inter-individual variability in PBL background damage and in radio-sensitivity (patients vs. healthy donors). In particular, they showed an increased radio-sensitivity in 36% and 33% of patients, decrease in 36% and 44%, respectively. There was a scarce correlation between the two assays and no dependence on age or gender. A significant association was found between high radio-sensitivity conditions and induced hypothyroidism. PBL radio-sensitivity in the patient group was not significantly affected by treatment with I-131, whereas there were significant changes inter-individually. The association found between clinical response and PBL radio-sensitivity suggests that the latter could be used in view of the development of personalized treatments.

Violet led dental whitening: Effectiveness and biological safety: An in vitro study.

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.

Micronucleus count in nasal epithelial cells from patients with chronic rhinosinusitis and polyps / Contagem de micronúcleos em células epiteliais nasais de pacientes com rinossinusite crônica e pólipos

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.

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.

Micronucleus in exfoliated buccal cells of crack users: systematic review and meta-analysis / Micronúcleos en células bucales exfoliadas en consumidores de crack: una revisión sistemática y meta-análisis

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.

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.

Genomic Instability in Exfoliated Buccal Cells among Cement Warehouse Workers.

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.

Micronucleus count in nasal epithelial cells from patients with chronic rhinosinusitis and polyps.

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.

Efeitos citotóxicos do aripiprazol nas linhagens celulares MKN45 e NIH3T3 e efeitos genotóxicos nos linfócitos sanguíneos periféricos humanos / Cytotoxic effects of aripiprazole on mkn45 and nih3t3 cell lines and genotoxic effects on human peripheral blood lymphocytes

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.

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.

Short-term "in vivo" study on cellular DNA damage induced by acrylic Andresen activator in oral mucosa cells.

OBJECTIVES: To analyse through comet assay and micronucleus test the viability and DNA damage occurred in buccal mucosa epithelial cells after a short-term exposure to Andresen activator resin monomers. SETTING AND SAMPLE POPULATION: Test group consisting of 26 subjects was treated with Andresen activator; 16 subjects who had never undergone orthodontic treatment were enrolled in the control group. MATERIAL & METHODS: Buccal mucosa samples were collected before treatment and after 7, 15, 30, 60 and 90 days. The analyses performed on the cells included the following: cellular viability, comet assay and micronucleus test. Mean ± SD were calculated for cellular viability, tail moment, tail intensity, tail length, micronuclei, binuclear and bud cells. Significance (P < 0.05) was evaluated with Dunnett's test. RESULTS: Cellular viability did not change during observational time, and its trend was similar to the controls. Tail moment and tail intensity significantly increased after 30 and 60 days, respectively, whereas tail length remained unchanged over time in the test group; the same parameters did not change in the control group. In the test group, micronuclei, binuclear and bud cells significantly increased after 30, 60 and 90 days, respectively. CONCLUSION: The resin monomers of the Andresen activator cause genotoxic effects detectable through comet assay and micronucleus test, but they do not produce clear cytotoxic effects after a 90 days exposure.

Chromosomal instability and cytotoxicity induced by ribavirin: comparative analysis in cell lines with different drug-metabolizing profiles.

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.