EMF INDUCED SIGNAL TRANSDUCTION AND GENE EXPRESSION

EMF 诱导信号转导和基因表达

• 批准号: 2518674
• 负责人: STEVEN C MILLER
• 金额: $ 28.96万
• 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 1999-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2518674
• 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​​磁场的生物效应 （EMF）存在争议，基本原则尚未达成共识 可能涉及。 尽管有多个互动站点 细胞水平，如离子通道、间隙连接和分子 信号转导途径的组成部分，已被建议为 电磁场调制的可能目标，但几乎没有直接证据。 体内和体外研究的最新结果表明，功率 频率 EMF 可能与化学肿瘤发挥共同促进活性 启动子 12-O-四癸酰佛波醇-13-乙酸酯 (TPA.) 60赫兹曝光系统被用来研究其机制 电磁场可能会促进癌症。 初步研究是 旨在评估工频电动势可能会产生的假设 放大TPA诱导的信号转导途径。他们的做法 是使用体外细胞培养模型来证明可重复性 EMF 的生物效应，以研究所涉及的细胞机制。 因为任何单一的体外模型系统都不可能 其本身就具有说服力，并且可能涉及多种机制 调节 EMF 效应，他们的方法是使用越来越多的 具体终点。肿瘤启动子反应性 JB6 细胞系将​​是 用于确定演示合作所需的 EMF 条件 TPA 和表皮生长因子 (EGF) 促进集落形成。 EMF和TPA对同源和异源间隙连接的影响 将使用流式细胞术染料转移来评估通信 化验。 此外，还建立了一个模型系统来研究 EMF 对 NF-κB 的激活并介导基因的激活 表达式的设计是为了进一步探讨之间的关系 钙、活性氧中间体 (ROI)、NF-kappaB DNA 结合、 HIV1-LTR 活性以及对 EMF 的反应。 因此，这些研究将 评估 EMF 可以通过以下方式放大信号转导的假设： 对作为活性氧产生的中间体有影响 信号转导的结果。