DNA mismatch repair gene methylation in gastric cancer in individuals from northern Brazil

Gastric cancer is one of the most common malignancies. DNA methylation is implicated in DNA mismatch repair genes deficiency. In the present study, we evaluated the methylation status of MLH1, MSH2, MSH6 and PMS2 in 20 diffuse- and 26 intestinal-type gastric cancer samples and 20 normal gastric mucosal of gastric cancer patients from Northern Brazil. We found that none of the nonneoplastic samples showed methylation of any gene promoter and 50% of gastric cancer samples showed at least one methylated gene promoter. Methylation frequencies of MLH1, MSH2, MSH6 and PMS2 promoter were 21.74%, 17.39%, 0% and 28.26% respectively in gastric cancer samples. MLH1 and PMS2 methylation were associated with neoplastic samples compared to nonneoplastic ones. PMS2 methylation was associated with diffuse- and intestinal-type cancer compared with normal controls. Intestinal-type cancer showed significant association with MLH1 methylation. Diffuse-type cancer was significantly associated with MSH2 methylation. Our findings show differential gene methylation in tumoral tissue, which allows us to conclude that methylation is associated with gastric carcinogenesis. Methylation of mismatch repair genes was associated with gastric carcinogenesis and may be a helpful tool for diagnosis, prognosis and therapies. However, MSH6 does not seem to be regulated by methylation in our samples.

Genotoxic effects of rotenone on cultured lymphocytes

Rotenone is a heterocyclic compound widely used as an insecticide, acaricide and piscicide. Its toxicity is mainly caused by the inhibition of mitochondrial respiratory processes and ATP production, resulting in the generation of reactive oxygen species. Reactive oxygen species can interact with DNA, RNA and proteins, leading to cell damage, followed by death. We used the Comet assay, and we analyzed chromosome aberrations, in order to evaluate the genotoxic and clastogenic effects of rotenone on the different phases of the cell cycle. Cultured human lymphocytes were treated with 1.0, 1.5 and 2.0 microg/mL rotenone during the G1, G1/S, S (pulses of 1 and 6 h), and G2 phases of the cell cycle. Rotenone induced DNA damage and was clastogenic, but the clastogenicity was detected only with treatments conducted during the G1/S and S phases of the cell cycle. Rotenone also induced endoreduplication and polyploidy in treatments made during G1, while it significantly reduced the mitotic index in all phases of the cell cycle.

Estudo da fragilidade cromossomica e cariotípico em pacientes com distúrbio bipolar do tipo I / Chromosomal fragility and karyotypic study in patients with type I bipolar disorder

Estudar a associaçäo de alteraçöes estruturais cromoss"micas particularmente de sítios fr geis, com distúrbio bipolar do tipo I. Planejamento: a) Investigaçäo de sítios fr geis: estudo caso-controle comparando pacientes bipolares com controles normais; b) investigaçäo cariotípica: estudo descritivo. Pacientes/participantes: Vinte e cinco casos com distúrbio bipolar do tipo I diagnosticados de acordo com os critérios do DSM-III-R através do Composite International Diagnostic Interview (CIDI), foram selecionados do programa ambulatorial de distúrbios afetivos da Escola Paulista de Medicina. Para o estudo de sítios fr geis, dez deles foram emparelhados por sexo e idade com dez controles sadios (CIDI negativos para distúrbios psiqui tricos) provenientes do ambulatório geral de otorrinolaringologia da mesma instituiçäo. Intervençäo: An lise citogenètica foi realizada em linfócitos sanguíneos cultivados em: a) meio pobre em folatos para a investigaçäo de sítios fr geis; b) meio padräo para o estudo cariotípico. Aferiçäo: a) Estudo de sítios fr geis: cem mitoses por indivíduo foram analisadas em teste cego ao diagnóstico psiqui trico. Os sítios fr geis foram identificados de acordo com uma frequência mínima de eventos esperada por banda de acordo com uma distribuiçäo de Poisson; b) Estudo cariotípico: 16 mitoses por indivíduo foram analisadas tentando-se identificar possíveis alteraçöes estruturais cromoss"micas cujos pontos de quebra possam sugerir locais de genes associados ao distúrbio bipolar. Resultados: a) Estudos de sítios fr geis: foi encontrada entre os casos maior frequência de lesöes nas seguintes bandas: 1q32, 5q31 e 11q23, sendo 1q32 o único sítio considerado fr gil; b) estudo cariotípico: näo foram evidenciadas alteraçöes estruturais cromoss"micas nem numéricas. Conclusöes: Apesar de que até o momento nenhum componente etiológico aparentemente envolvido em distúrbios neuro-psiqui tricos tenha sido mapeado na regiäo 1q32, estes achados podem levar a futuras investigaçöes de possível ligaçäo entre marcadores genéticos desta regiäo e o distúrbio bipolar