EFFECTS AND MECHANISMS OF EMF SIGNAL TRANSDUCTION

电磁场信号传导的效应和机制

• 批准号: 2156199
• 负责人: SEK-WEN HUI
• 金额: $ 16.91万
• 依托单位: ROSWELL PARK CANCER INSTITUTE
• 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/2156199
• 关键词: biological signal transduction; calcium channel blockers; calcium flux; calcium transporting ATPase; calmodulin; cell cycle; electromagnetic radiation; enzyme activity; fibroblasts; gene expression; lymphoblast; methylcholanthrene; neoplastic transformation; phenotype; phorbols; protein kinase C; protooncogene; radiation carcinogenesis; radiation dosage; radiation genetics; radiobiology; retinoids; second messengers; tissue /cell culture; tumor promoters

DESCRIPTION: The goal of this proposal is to substantiate certain reported effects of weak, 60 Hz electromagnetic fields on cell functions, and to define a cellular mechanism for the effects. The proposed work begins with an attempt to reproduce c-myc proto-oncogenes in CEM-CM3 T-lymphoblastoid cells. A magnetic field exposure system with identical sham set-up will be built to duplicate the setting. After the further experiments employing 60 Hz electric fields of 2-200 Mv/m alone, (corresponding to about 3-300 mA/m(2) of current density in the culture medium), or in addition to magnetic field and its induced current, will be performed. To amplify the electromagnetic field effect on carcinogenesis, a two-stage carcinogenesis model system, i.e., the methylcholanthrene-initiated, retinoid suppressed C3H/10T(1/2) fibroblasts, will be used to test the hypothesis that electromagnetic field acts as a promoter rather than as an initiator. The timing and the extent of expression of the transformed phenotype, proto-oncogene expression, and proliferation of initiated cells will be determined.Electromagnetic field-induced calcium signals in these cells and in lymphoblastoid cells will be measured and related to protein kinase C activation and other downstream functions, to test the hypothesis that electromagnetic field-induced calcium influx is a primary or secondary messenger in transducing signals related to carcinogenic promotion. The origin and mechanism of inducing calcium signals by electromagnetic field will be investigated, by using channel blockers, calmodulin inhibitors, and calcium pump modulators, and by matching the response frequency windows with hypothetical resonance amplification by intra-, extra-, and trans-membrane circuits. The outcome is expected to explain, and to define the significance limits of biological effects of weak electromagnetic field corresponding to environmental exposures.

描述：该提议的目的是确定一定 报道的弱，60 Hz电磁场对细胞的影响 功能，并定义效果的细胞机制。 这 拟议的工作始于试图再现C-Myc原源性基因 在CEM-CM3 T淋巴细胞中。带有磁场暴露系统 相同的假设置将被构建以复制设置。 之后 仅使用60 Hz电场的进一步实验，仅2-200 mV/m， （对应于培养物中电流密度约3-300 mA/m（2） 中等），或除了磁场及其诱导电流外，还将 被执行。 扩增电磁场对 致癌作用，一种两阶段的癌变模型系统，即 胆醇素引发的类视黄素抑制了C3H/10T（1/2） 成纤维细胞将用于测试电磁的假设 现场充当促进者，而不是发起人。 时机和 转化表型的表达程度，原始癌基因 表达和引发细胞的增殖将是 确定这些细胞中电磁场诱导的钙信号 并将测量淋巴母细胞中的细胞并与蛋白质有关 激酶C激活和其他下游功能，以测试 假设电磁场诱导的钙涌入是主要的 或次级信使在与致癌有关的传输信号中 晋升。 通过 通过使用通道阻滞剂，将研究电磁场 钙调蛋白抑制剂和钙泵调节剂，并通过匹配 通过假设共振扩增的响应频率窗口 内部，外部和跨膜电路。 结果有望 解释并定义生物学效应的显着性限制 与环境暴露相对应的弱电磁场。