MODELS FOR IDENTIFYING POTENTIAL ENVIRONMENTAL CARCINOGENS IN EM FIELDS

识别电磁场中潜在环境致癌物的模型

• 批准号: 6450694
• 负责人: Ann S Henderson
• 金额: $ 5.95万
• 依托单位: HUNTER COLLEGE
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-04-01 至 2002-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6450694
• 关键词: biological signal transduction; cell line; cell transformation; cellular oncology; cellular pathology; densitometry; electromagnetic radiation; environmental radiation; enzyme activity; enzyme linked immunosorbent assay; flow cytometry; ion exchange chromatography; lipid metabolism; magnetic field; neoplastic transformation; protein kinase; protein kinase C; radiation carcinogen; radiation dosage; radiation hazard; thin layer chromatography; tissue /cell culture; tumor promoters; western blottings

The possibility that electromagnetic fields (EMF) can alter cell activity which augments tumorigenic processes is controversial, yet persistent, and the dispute must be resolved. Epidemiological and biological studies associate EMF exposure with a potential for increased cancer incidence, but the evidence is inconsistent. This research will confirm or negative the proposed correlation between EMF and health effects-or any other outcomes. The studies build in a systematic approach to determine measurable consequences of EMF exposure in the whole cell- identification of morphological endpoints dissect pertinent transduction pathways-correlating morphological endpoints with mechanisms; do the molecular endpoints have a logical relationship to proposed effects of EMF? and devise surrogate tests for testing tumorigenicity of EMF- relating morphological or molecular endpoints to cell transformation. A driving force was finding a clear endpoint for measurement of the consequences of EMF exposure. Induced cellular differentiation in hemopoietic progenitor cells by phorbol esters is a perfect paradigm; EMF also induces differentiation. This endpoint is invaluable since many signaling pathways are pinpointed in induced differentiation and overlap those involved in growth control. Here, identifiable pathways resulting from EMF induced differentiation and those used in pathways leading to tumor promotion will be compared. Two surrogate tests for analyzing the tumorigenic potential of EMF will also be used. Differentiation provides one test since relative induction of differentiation is proportional to known in vivo promoting activity of phorbol esters. A more definitive in vitro assay to measure cell transformation, however, is pivotal to solving the controversy of whether EMF can transform cells. The test will use cells that over express the non-receptor tyrosine kinase c-Src. These cells show morphological transformation consistent with v-Src and form colonies in soft agar with TPA treatment. Thus, tests for transforming ability will be made in cells that have a preexisting "mutation", consistent with proposed mechanisms for EMF.

电磁场（EMF）可以改变细胞活性从而增强肿瘤发生过程的可能性是有争议的，但持续存在，争议必须得到解决。流行病学和生物学研究将EMF暴露与癌症发病率增加的可能性联系起来，但证据不一致。这项研究将证实或否定电磁场和健康效应或任何其他结果之间的相关性。这些研究建立在一个系统的方法，以确定可测量的后果，电磁场暴露在整个细胞-识别的形态学终点解剖相关的转导途径-相关的形态学终点与机制;分子终点有一个逻辑关系，提出的影响电磁场？ 并设计用于测试EMF致瘤性的替代测试--将形态学或分子学终点与细胞转化相关联。一个驱动力是找到一个明确的终点测量电磁场暴露的后果。通过佛波醇酯诱导造血祖细胞的细胞分化是一个完美的范例; EMF也诱导分化。这个终点是非常宝贵的，因为许多信号通路在诱导分化中被精确定位，并且与参与生长控制的那些信号通路重叠。在这里，可识别的途径导致电磁场诱导分化和那些用于导致肿瘤促进的途径将进行比较。还将使用两种替代试验分析EMF的致瘤潜力。 分化提供了一种测试，因为分化的相对诱导与佛波醇酯的已知体内促进活性成比例。 然而，一个更明确的体外测定细胞转化的方法是解决EMF是否能转化细胞的争议的关键。该试验将使用过表达非受体酪氨酸激酶c-Src的细胞。这些细胞显示出与v-Src一致的形态转化，并在TPA处理的软琼脂中形成集落。因此，转化能力的测试将在具有预先存在的“突变”的细胞中进行，这与EMF的拟议机制一致。