Recent epidemiological studies have yielded a large body of evidence that is suggestive of a causal link between extremely low frequency (ELF) electromagnetic (EM) field exposure and cancer induction. Since little is known regarding the EMF """"""""dose"""""""" that individuals received, or the duration of their exposure, the link from these epidemiological investigations is somewhat tenuous. Experimental data, thus far, tends to confirm the connection between ELF EM field exposure and possible adverse effects on animal and cellular systems in that a number of positive results were obtained. Interpretation of data from these investigations is difficult due to differing exposure conditions between laboratories and difficulties encountered in replicating some studies. Endpoints in which positive correlations have been found include perturbations to the cell cycle, alterations to cellular membranes, disturbances of calcium flux and enzyme levels, altered gene expression, abolition of pineal circadian rhythm for melatonin synthesis and secretion, and reduced immunocompetence.A number of these findings point towards ELF EM exposure acting as an initiator of carcinogenesis while others suggest promotional mechanisms. The question of whether ELF EM exposure alters the carcinogenic response remains unresolved. Their laboratory has considerable experience quantifying and characterizing the molecular alterations associated with ionizing-radiation induced oncogenic transformation. Unlike ELF electromagnetic radiation, ionizing radiation possesses sufficient energy to disrupt DNA bonds and thus lead towards cancer initiation directly. Recent studies indicate the presence of a cell cycle """"""""window"""""""" of sensitivity for oncogenic transformation by ionizing radiation which is dependent on the radiation quality. In light of these findings, and data which point towards EMF exposure altering cell cycle times and influencing transcription of genes which are fundamentally important to cell cycle regulation, it is conceivable that ELF/EMF exposure may induce, or enhance, oncogenic transformation by modifying the normal cell proliferative pathway. EMF may, however, exert effects which ultimately influence oncogenic transformation via promotional events which are unrelated to cell cycle regulation. The present proposal seeks to address these points by monitoring transcription levels of c-fos, c-jun, and c-myc and cell cycle regulatory genes (Rb, p53, cdc2, cyclin A, and cyclin B) following ELF EMF exposure (60 Hz.) Perturbations of the cell cycle will be monitored by cytofluorimetric determinations. These investigations will be carried out in three different cell lines, human (HeLa) fibroblasts, mouse (C3H 10T1/2) fibroblasts (a cell line which will also be used to quantify oncogenic transformation) and human mammary epithelial cells (MCF-10.) The induction, or promotion, of in vitro oncogenic transformation in C3H 10T1/2 cells, by exposure to ELF EM fields, will be studied by using EM fields alone or in conjunction with TPA or X-rays. The influence of field strength and duration of exposure will also be investigated during the course of these studies.
