RESPONSE OF CANCER RELEVANT CELLS TO EMF

癌症相关细胞对 EMF 的反应

• 批准号: 2156179
• 负责人: JERRY R WILLIAMS
• 金额: $ 29.92万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 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/2156179
• 关键词: cell cycle; chemical synthesis; electromagnetic radiation; free radical oxygen; gene expression; gene mutation; genotype; ionizing radiation; neoplasm /cancer genetics; neoplastic process; oncogenes; ornithine decarboxylase; polyamines; radiation carcinogen; radiation carcinogenesis; radiation dosage; radiation genetics; radiobiology; tissue /cell culture; tumor suppressor genes

DESCRIPTION: Human populations live in an environment permeated with electric and magnetic fields. Whether this exposure presents a health hazard is controversial, supported by some data but not others. The investigators propose to determine whether cells with documented relevance to the cancer process respond to EMF exposure, and whether such response is consistent with their current understanding of carcinogenic and/or co-carcinogenic processes. They also propose careful repetition of two seminal observations: that EMF induces enhanced expression of one member of the myc family of oncogenes, and that it also alters levels of the growth-related enzyme, ornithinine decarboxylase (ODC.) They have studied myc expression and its effect on tumor progression in a well-documented lung cancer system in which myc- induced progression can be documented by phenotypic changes. Thus, changes in myc expression can be documented not only at the transcriptional level and its downstream molecular sequelae, but also by phenotypic changes in cell morphology, growth requirements and resistance to challenges with carcinogens and inhibitors of polyamine synthesis. This last observation, resistance to inhibitors of polyamine synthesis, offers a modality to select a minority population of resistant cells, if such cells are induced by transient exposures to EMF. Recent studies by others describe a myc binding site on the ODC promoter, suggesting a mechanistic relationship between myc expression and control of ODC expression. They will investigate this possible relationship in EMF treated cells. Thus, their studies will not only attempt to reproduce previously reported data, but will extend these data to systems and endpoints relevant to the cancer process. EMF has been proposed as a co-carcinogen that could interact with carcinogens such as ionizing radiation, or with constitutive cellular processes such as oxygen radicals, or with proliferation itself. Such interaction, it is proposed, could produce the several mutations in oncogenes and tumor suppressor genes that constitute the cancer genotype. They have developed a cell system that is hypermutable to cellular proliferation, reflecting a defect in base mismatch repair. Thus, agents such as EMF, purported to interact with cellular proliferation can now be evaluated as to whether they have the ability to induce mutation in these hypersensitive cells. This system also offers a sensitive assay for interaction between EMF and low level ionizing radiation and for possible protective effects of melatonin. These proposed studies will determine whether EMF induces cancer-related changes in human cells and will seek to establish such changes, if they occur, in a framework that will permit initial testing of two important hypotheses relating EMF effects to cancer induction.

描述：人类人口生活在渗透的环境中 电场和磁场。 这种暴露是否呈现健康 危险是有争议的，在某些数据的支持下，但没有其他数据支持。 这 调查人员建议确定是否有记录的单元 与癌症过程有关的相关性应对电动势暴露，以及是否 这种反应与他们当前对 致癌和/或共同致癌过程。 他们还谨慎 重复两个开创性观察：EMF引起了增强 MYC癌基因家族的一位成员的表达 还改变了与生长相关的酶，鸟嘌呤的水平 脱羧酶（ODC。）他们研究了MYC的表达及其对 肿瘤的进展在有据可查的肺癌系统中 诱导的进展可以通过表型变化记录。 因此， MYC表达的变化不仅可以记录在 转录水平及其下游分子后遗症，但也 通过表型的细胞形态变化，生长需求和 对多胺的致癌物和抑制剂的挑战的抗性 合成。 最后观察到对多胺抑制剂的抗性 合成，提供了选择的方式来选择少数人口 抗性细胞，如果通过瞬态暴露诱导此类细胞 EMF。 其他人的最新研究描述了ODC上的MYC结合位点 发起人，提出MYC表达之间的机械关系 和控制ODC表达。 他们会调查这一点 EMF处理的细胞中的关系。 因此，他们的研究不仅会 尝试重现先前报告的数据，但会扩展这些数据 与癌症过程相关的系统和端点的数据。 EMF已被提议为一种可以与 致癌物（例如电离辐射）或构成性细胞 氧自由基或增殖本身等过程。 这样的 提出的相互作用可能会产生几个突变 构成癌症的癌基因和肿瘤抑制基因 基因型。 他们已经开发了一个细胞系统，该系统可超过 细胞增殖，反映基础不匹配修复中的缺陷。 因此，诸如EMF之类的药物据称与细胞相互作用 现在可以评估扩散是否有能力 诱导这些超敏细胞中的突变。 此系统也是如此 为EMF和低水平之间的相互作用提供了敏感的测定 电离辐射和褪黑激素的可能保护作用。 这些拟议的研究将确定EMF是否诱导癌症相关 人类细胞的变化，并试图建立这种变化，如果它们 发生在一个框架中，该框架将允许对两个重要的初步测试 假设EMF效应与癌症诱导有关。