Monitorização citogenética de dentistas brasileiros ocupacionalmente expostos a baixos níveis de radiação X

A exposição à radiação ionizante pode causar aberrações cromossômicas (AC) em células somáticas ou germinativas dos indivíduos expostos, podendo levar a manifestações de doenças como os cânceres. Este trabalho teve como objetivo avaliar a freqüência de AC em linfócitos obtidos através de cultura temporária do sangue periférico de dentistas de Londrina (Paraná - Brasil), com mais de dez anos de trabalho com raios X. Os resultados obtidos do grupo experimental foram comparados com um grupo controle negativo pareado, que nunca se expôs ocupacionalmente aos raios X. Todos os indivíduos, dentistas e controles, responderam a um questionário pessoal, a partir do qual foi obtido um perfil de cada grupo. Após as culturas, as lâminas foram confeccionadas, coradas com solução de Giemsa e foram analisadas de 100 a 200 células metafásicas por indivíduo, anotando-se as freqüências e tipos de AC encontrados. Não foi necessária a realização de testes estatísticos para avaliação desses parâmetros. A análise dos índices mitóticos (IM) não indicou diferenças significantes (p < 0,05) entre os indivíduos dos grupos expostos e controle. Os fatores de variação analisados não influenciaram os resultados obtidos para o IM e freqüência de AC.Exposure to X-rays (ionizing radiation) may cause chromosomal aberrations (CA) in somatic or germinative cells in exposed individuals, and may lead to manifestations of diseases such as cancer. This study was carried out to assess the CA frequency in lymphocytes obtained by means of temporary culture of peripheral blood from dentists in Londrina, Paraná, Brazil, who have worked for more than ten years with X-rays. The results obtained from the experimental group were compared with a matched negative control group, which had never been exposed to X-rays. All individuals, dentists and controls, answered a personal questionnaire, from which a profile of each group was obtained. Slides, prepared after the cultures, were stained with Giemsa, and 100 to 200 metaphase cells were analyzed per individual. CA frequencies and types were registered and statistical tests were not necessary to evaluate the obtained data. The analysis of mitotic index (MI) did not indicate significant differences (p < 0.05) between the group of individuals exposed to X-rays and the control group. The analyzed confounding factors did not influence the results of MI and CA frequencies

Genome-wide methylation and transcriptome analysis in penile carcinoma: uncovering new molecular markers

Background: Despite penile carcinoma (PeCa) being a relatively rare neoplasm, it remains an important public health issue for poor and developing countries. Contrary to most tumors, limited data are available for markers that are capable of assisting in diagnosis, prognosis, and treatment of PeCa. We aimed to identify molecular markers for PeCa by evaluating their epigenomic and transcriptome profiles and comparing them with surrounding non-malignant tissue (SNT) and normal glans (NG).Results: Genome-wide methylation analysis revealed 171 hypermethylated probes in PeCa. Transcriptome profiling presented 2,883 underexpressed and 1,378 overexpressed genes. Integrative analysis revealed a panel of 54 genes with an inverse correlation between methylation and gene expression levels. Distinct methylome and transcriptome patterns were found for human papillomavirus (HPV)-positive (38.6%) and negative tumors. Interestingly, grade 3 tumors showed a distinct methylation profile when compared to grade 1. In addition, univariate analysis revealed that low BDNF methylation was associated with lymph node metastasis and shorter disease-free survival. CpG hypermethylation and gene underexpression were confirmed for a panel of genes, including TWIST1, RSOP2, SOX3, SOX17, PROM1, OTX2, HOXA3, and MEIS1.Conclusions: A unique methylome signature was found for PeCa compared to SNT, with aberrant DNA methylation appearing to modulate the expression of specific genes. This study describes new pathways with the potential to regulate penile carcinogenesis, including stem cell regulatory pathways and markers associated to a worse prognosis. These findings may be instrumental in the discovery and application of new genetic and epigenetic biomarkers in PeCa.Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES

Protective effect of carboxymethyl-glucan (CM-G) against DNA damage in patients with advanced prostate cancer

Carboxymethyl-glucan (CM-G) is a soluble derivative from Saccharomyces cerevisiae (1 → 3)(1 → 6)-β-D-glucan. The protective efficiency of CM-G against DNA damage in cells from patients with advanced prostate cancer (PCa), and undergoing Androgen Deprivation Therapy (ADT), was evaluated. DNA damage scores were obtained by the comet assay, both before and after treatment with CM-G. The reduction in DNA damage, ranging from 18% to 87%, with an average of 59%, was not related to the increased number of leukocytes in peripheral blood. The results demonstrate for the first time the protective effect of CM-G against DNA damage in patients with advanced PCa. Among smokers, three presented the highest reduction in DNA damage after treatment with CM-G. There was no observable relationship between DNA damage scores before and after treatment, and age, alcoholism and radiotherapy

Mushroom Shiitake, is it mutagenic or antimutagenic agent? <br> Shiitake, um cogumelo mutagênico ou antimutagênico?

Mushrooms have been consumed by eastern populations due to their edible and medicinal properties, for a long time. Over the years, there has also been a gradual increase in the consumption of mushrooms in the western countries, including Brazil. However, the benefits or harms that these mushrooms may cause to the human health are still uncertain. Shiitake (Lentinula edodes (Berk.) Pegler) is one of the most appreciated fungi in the Brazilian cuisine and its functional and nutritional properties have been extensively studied. Other characteristics of this basidiomycet have also been reported, including its antitumoral, antiviral, bactericidal properties, as well as being a homeostasis and biorhythm regulator. However, studies regarding its mutagenic and antimutagenic potential in prokaryotic and eukaryotic organisms are scarce. Knowledge of these biological properties is essential before a product can be recommended as food and/or drug. Therefore, its indication as a beneficial product to human health is premature since it is necessary to broaden studies on the mutagenic and antimutagenic activities of the mushroom Shiitake or of its active compounds.   <p><p>Desde a antigüidade, os cogumelos vêm sendo consumidos pelos povos orientais devido às suas  propriedades medicinais e comestíveis e ao longo dos anos tem-se observado um aumento gradativo no consumo também nos países ocidentais, inclusive o Brasil. No entanto, ainda há dúvidas quanto aos benefícios ou prejuízos à saúde, decorrentes do uso destes cogumelos pelas populações humanas. Entre os cogumelos muito apreciados na culinária brasileira, destaca-se o Shiitake (Lentinula edodes (Berk.) Pegler), um dos fungos comestíveis mais estudados quanto às suas propriedades funcionais e nutricionais. Já se tem conhecimento sobre várias atividades deste basidiomiceto superior, como antitumoral, antiviral, bactericida, regulador da homeostase e do biorritmo. No entanto, poucos trabalhos abordam suas propriedades mutagênicas e antimutagênicas em organismos procariontes e eucariontes e o conhecimento dessas propriedades biológicas são importantes para que um produto seja recomendável como alimento e/ou medicamento. Dessa forma, é prematura sua recomendação para a saúde humana, pois é necessário, para isso, a ampliação de estudos sobre as atividades mutagênicas e antimutagênicas do cogumelo Shiitake ou de seus compostos ativos.

Epigenetic mechanisms in penile carcinoma

Penile carcinoma (PeCa) represents an important public health problem in poor and developing countries. Despite its unpredictable behavior and aggressive treatment, there have only been a few reports regarding its molecular data, especially epigenetic mechanisms. The functional diversity in different cell types is acquired by chromatin modifications, which are established by epigenetic regulatory mechanisms involving DNA methylation, histone acetylation, and miRNAs. Recent evidence indicates that the dysregulation in these processes can result in the development of several diseases, including cancer. Epigenetic alterations, such as the methylation of CpGs islands, may reveal candidates for the development of specific markers for cancer detection, diagnosis and prognosis. There are a few reports on the epigenetic alterations in PeCa, and most of these studies have only focused on alterations in specific genes in a limited number of cases. This review aims to provide an overview of the current knowledge of the epigenetic alterations in PeCa and the promising results in this field. The identification of epigenetically altered genes in PeCa is an important step in understanding the mechanisms involved in this unexplored disease. © 2013 by the authors; licensee MDPI, Basel, Switzerland

Evaluation of the genotoxicity and fetal toxicity of the herbicide Paraquat Avaliação da genotoxicidade e da toxicidade fetal do herbicida Paraquat

A genotoxicidade e a toxicidade fetal do Paraquat foram avaliadas em camundongos fêmeas após tratamento agudo e subcutâneo do herbicida em diferentes períodos gestacionais. Foram utilizados o teste do micronúcleo (MN) em eritrócitos de sangue periférico e a avaliação de perdas embrionárias. Os resultados deste trabalho mostraram que o tratamento agudo com a menor dose testada, 10mg/kg pc (peso corpóreo), no período de pós-implantação, não produziu diminuição significativa do tamanho da prole. Observou-se genotoxicidade 24 e 30 horas após o tratamento de animais que receberam esta dosagem no 9º e 3º dia de prenhez, respectivamente. Nossos dados sugerem, ainda, que o tratamento <em>in vivo</em>, com a menor dose, induz perdas embrionárias em fêmeas expostas ao agente no período de pré-implantação. A dose de 20mg/kg pc não mostrou efeito genotóxico após 24 horas do tratamento, provavelmente por ter induzido seleção celular devido à alta toxicidade do herbicida. Esta dose causou a morte dos animais, impedindo as análises de MN após 30 horas do tratamento e da toxicidade fetal.<br>The genotoxicity and fetal toxicity of the herbicide Paraquat was assessed in female mice treated with acute subcutaneous doses of the herbicide at different stages of pregnancy. The micronucleus test (MN) in peripheral blood erythrocytes and an evaluation of embryonic losses were applied. The results of the present work demonstrate that a single acute treatment in the period after-implantation did not produce a significant reduction in the size of the offspring at the lower dosage tested, 10 mg/kg bw (body weight). Genotoxicity was observed at 24 and 30 hours after treatment in animals receiving this dosage on the ninth and third day of pregnancy respectively. Our data suggest that the <em>in vivo</em> treatment with the lower herbicide dose induces embryonic losses in females exposed to the agent during the pre-implantation period. The dose of 20 mg/kg bw did not show genotoxic effects 24 hours after treatment, probably having induced cellular defenses due to high toxicity of the herbicide. This dose subsequently caused the death of the animals, hindering the analyses of MN at 30 hours post-treatment and of fetal toxicity determinations