RESUMO
Occupational and environmental asbestos exposure is the main determinant of malignant pleural mesothelioma (MPM), however, the mechanisms by which its fibres contribute to cell toxicity and transformation are not completely clear. Aberrant DNA methylation is a common event in cancer but epigenetic modifications involved specifically in MPM carcinogenesis need to be better clarified. To investigate asbestos-induced DNA methylation and gene expression changes, we treated Met5A mesothelial cells with different concentrations of crocidolite and chrysotile asbestos (0.5 ÷ 5.0 µg/cm2, 72 h incubation). Overall, we observed 243 and 302 differentially methylated CpGs (≥ 10%) between the asbestos dose at 5 µg/cm2 and untreated control, in chrysotile and crocidolite treatment, respectively. To examine the dose-response effect, Spearman's correlation test was performed and significant CpGs located in genes involved in migration/cell adhesion processes were identified in both treatments. Moreover, we found that both crocidolite and chrysotile exposure induced a significant up-regulation of CA9 and SRGN (log2 fold change > 1.5), previously reported as associated with a more aggressive MPM phenotype. However, we found no correlation between methylation and gene expression changes, except for a moderate significant inverse correlation at the promoter region of DKK1 (Spearman rho = - 1, P value = 0.02) after chrysotile exposure. These results describe for the first time the relationship between DNA methylation modifications and asbestos exposure. Our findings provide a basis to further explore and validate asbestos-induced DNA methylation changes, that could influence MPM carcinogenesis and possibly identifying new chemopreventive target.
Assuntos
Amianto/toxicidade , Metilação de DNA/efeitos dos fármacos , Transcriptoma/efeitos dos fármacos , Antígenos de Neoplasias/genética , Amianto/química , Asbesto Crocidolita/administração & dosagem , Asbesto Crocidolita/toxicidade , Asbestos Serpentinas/administração & dosagem , Asbestos Serpentinas/toxicidade , Anidrase Carbônica IX/genética , Linhagem Celular , Relação Dose-Resposta a Droga , Células Epiteliais/efeitos dos fármacos , Humanos , Neoplasias Pulmonares/induzido quimicamente , Neoplasias Pulmonares/genética , Mesotelioma/induzido quimicamente , Mesotelioma/genética , Mesotelioma Maligno , Reação em Cadeia da Polimerase em Tempo RealRESUMO
A total of 41 experiments were conducted in the context of the Euromir 95 mission, in the categories of life sciences, materials science, astrophysics and technology (Table 1). First results were presented recently at a post-flight Investigator Working Group Meeting at the European Astronauts Centre in Cologne, Germany. This article summarises all but those of the life-sciences experiments, which will be published separately at a later date.
Assuntos
Pesquisa , Voo Espacial/instrumentação , Ausência de Peso , Medicina Aeroespacial , Microbiologia Ambiental , Monitoramento Ambiental , Humanos , Teste de Materiais , Meteoroides , Tamanho da Partícula , Monitoramento de Radiação/instrumentação , RobóticaRESUMO
Microbiological sampling techniques, earth-radiation-environment monitoring, gas-contaminant bio-filtering tools, multimedia communications technology, passive magnetic-levitation techniques for fluid-dynamics study, robotics-technology development, gas-sensor systems and analysis tools for human kinematics in microgravity--all were a part of the truly multidisciplinary Technology Experiments package flown aboard the record-breaking EuroMir 95 mission. Final processing and evaluation of the vast amount of data gathered from the experiments will not be completed until the end of the year--work is currently in progress at nine different centres throughout Europe--and this article therefore provides but a first glimpse of the mission's many findings and their implications for long-term manned spaceflight in the context of the International Space Station.
