MODELS FOR IDENTIFYING POTENTIAL ENVIRONMENTAL CARCINOGENS IN EM FIELDS

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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.