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.
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