EMF INDUCED SIGNAL TRANSDUCTION AND GENE EXPRESSION

EMF 诱导信号转导和基因表达

• 批准号: 2156262
• 负责人: STEVEN C MILLER
• 金额: $ 19.87万
• 依托单位: SRI INTERNATIONAL
• 依托单位国家: 美国
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-09-28 至 1998-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2156262
• 关键词: RNase protection assay; biological signal transduction; chloramphenicol acetyltransferase; electromagnetic radiation; epidermal growth factor; flow cytometry; free radical oxygen; gap junctions; gene expression; gene induction /repression; membrane channels; messenger RNA; phorbols; posttranscriptional RNA processing; radiation dosage; radiation genetics; radiation sensitivity; tissue /cell culture

DESCRIPTION: The biological effects of low-energy electromagnetic fields (EMFs) is controversial with no consensus of the fundamental principles potentially involved. Although several sites of interaction at the cellular level, such as ion channels, gap junctions, and molecular components of signal transduction pathways, have been suggested as likely targets for modulation by EMFs, there is little direct evidence. Recent results from in vivo and in vitro studies suggest that power frequency EMFs may exert co-promoting activity with the chemical tumor- promoter 12-O-tetra-decanoylphorbol-13- acetate (TPA.) A 60-Hz exposure system is being used to study the mechanism by which EMFs may potentially act to promote cancer. Preliminary studies were designed to evaluate the hypothesis that power frequency EMFs may amplify the signal transduction pathway induced by TPA. Their approach is to use in vitro cell culture models demonstrating reproducible biological effects of EMFs to study the cellular mechanisms involved. Because it is unlikely that any single in vitro model system will be convincing on its own and multiple mechanisms may be involved in mediating EMF effects, their approach is to use increasingly more specific endpoints.The tumor-promoter-responsive JB6 cell line will be used to determine the EMF conditions required for demonstrating co- promotion of colony formation by TPA and epidermal growth factor (EGF.) The effect of EMF and TPA on homologous and heterologous gap junctional communication will be evaluated by using a flow cytometric dye-transfer assay. Further, a model system to investigate the effect of EMFs on the activation of NF-kappaB and in mediating the activation of gene expression has been devised to further explore the relationship between calcium, reactive oxygen intermediates (ROIs), NF-kappaB DNA-binding, HIV1-LTR activity, and the response to EMFs. Thus, these studies will evaluate the hypothesis that EMFs may amplify signal transduction by having an effect on reactive oxygen intermediates produced as a consequence of signal transduction.

描述：低能电​​磁场的生物学效应 （EMF）是有争议的，没有基本原则的共识 潜在参与。 虽然在 细胞水平，例如离子通道，间隙连接和分子 信号转导途径的组成部分已被认为为 EMF的调制可能是直接证据。 体内和体外研究的最新结果表明权力 频率EMF可能发挥与化学肿瘤的共同促进活性 启动子12-O-TETRA-DECANOYLPHORBOL-13-乙酸盐（TPA。） 一个60 Hz的暴露系统被用于研究 EMF可能有可能采取行动来促进癌症。 初步研究是 旨在评估功率频率EMF可能的假设 扩增TPA诱导的信号转导途径。他们的方法 是使用体外细胞培养模型证明可重复的 EMF研究所涉及的细胞机制的生物学作用。 因为任何单个体外模型系统都不太可能 说服自己和多种机制可能涉及 调解EMF效果，他们的方法是越来越多地使用 特定的终点。肿瘤促促响应者JB6细胞系将是 用于确定展示共同条件的EMF条件 TPA和表皮生长因子促进菌落形成（EGF。） EMF和TPA对同源和异源间隙连接的影响 通信将通过使用流式细胞仪染料转移来评估 测定。 此外，一个模型系统来研究EMFS对 NF-kappab的激活和介导基因的激活 已经设计了表达来进一步探索 钙，活性氧中间体（ROI），NF-kappab DNA结合， HIV1-LTR活性以及对EMF的响应。 因此，这些研究将 评估EMF可以扩增信号转导的假设 对作为A产生的活性氧中间体产生影响 信号转导的结果。