MODELS FOR IDENTIFYING POTENTIAL ENVIRONMENTAL CARCINOGENS IN EM FIELDS

电磁场(EMF)可以改变细胞活动从而增强肿瘤形成过程的可能性是有争议的，但仍然存在，这一争议必须得到解决。流行病学和生物学研究将电磁场暴露与癌症发病率增加的可能性联系起来，但证据并不一致。这项研究将证实或否定电动势与健康影响或任何其他结果之间的拟议相关性。这些研究建立了一种系统的方法来确定电磁场暴露在整个细胞中的可测量后果--识别形态终点，剖析相关的转导途径--将形态终点与机制联系起来；分子终点与所提出的电动磁场效应是否存在逻辑关系？并设计替代测试来测试EMF与细胞转化相关的形态或分子端点的致瘤性。一个驱动力是找到一个明确的终点来衡量电磁场暴露的后果。佛波酯诱导造血祖细胞分化是一个理想的范例；电磁场也可以诱导分化。这一终点是无价的，因为许多信号通路在诱导分化中被精确定位，并与涉及生长控制的信号通路重叠。在这里，将比较电磁场诱导分化所导致的可识别的途径和那些用于促进肿瘤的途径。还将使用两种替代测试来分析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已知的佛波酯在体内的促进活性成正比。然而，一种更明确的体外实验来测量细胞转化，是解决关于电磁场是否能转化细胞的争议的关键。这项测试将使用过度表达非受体酪氨酸激酶c-Src的细胞。这些细胞表现出与v-Src一致的形态变化，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，这与所提出的电动势机制是一致的。

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.