Item – Theses Canada

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OCLC number
806535869
Author
Buckner, Carly,1980-
Title
Effects of electromagnetic fields on biological processes are spatial and temporal-dependent.
Degree
Ph. D. -- Laurentian University, 2011
Publisher
Ottawa : Library and Archives Canada = Bibliothèque et Archives Canada, [2012]
Description
3 microfiches
Notes
Includes bibliographical references.
Abstract
<?Pub Inc> Although most studies describe the negative aspects of electromagnetic fields (EMFs) on health, EMFs can also be used to positively target specific biological processes. The current hypothesis is that the ability of EMFs to influence biological processes is dependent upon the temporal (timing) patterns of the fields, similar to the way pharmaceuticals are dependent upon their chemical structures. Thus, unique EMF patterns have been generated with the goal of targeting specific biological processes. "Thomas-EMF" is a time-varying frequency-modulated (25 Hz to 6 Hz) EMF pattern originally designed to target pain receptors. Unexpectedly, Thomas-EMF can also significantly inhibit malignant cell proliferation. The goal of this study was to use 'in vitro' and 'in vivo' models to determine the mechanism by which Thomas-EMF selectively inhibits malignant cell proliferation. The optimal parameters of the Thomas-EMF pattern that were crucial to the inhibition of malignant cell proliferation were examined. Exposure of malignant B16-BL6 mouse melanoma cells to the Thomas-EMF for 1 h/day inhibited cell proliferation in such that the number of cells decreased to 50% of sham-treated cells by 5 days of exposure. However, exposure to Thomas-EMF presented in reverse order (6 Hz to 25 Hz), in addition to fragments of the Thomas-EMF pattern (constant 6 Hz or constant 25 Hz), did not inhibit proliferation. These effects were also dependent upon timing within the pattern. For example, the point duration in Thomas-EMF that had the strongest effect was at 3 msec while 4 and 5 msec exhibited no effects. The involvement of signaling pathways in the Thomas-EMF-dependent growth inhibition was tested using an inhibitor-based approach. Our results showed that modulating cAMP levels by treatment with SQ22536 (an inhibitor) or Forskolin (an activator) abolished the Thomas-EMF effect on B16-BL6 proliferation. Further, enzyme-linked immunosorbant assay (ELISA) showed that exposure to Thomas-EMF caused a significant decrease in cAMP levels. Inhibitors blocking PKC, PI3 kinase, and calcineurin did not alter Thomas-EMF-dependent effects, however, inhibitors of ERK partially blocked the Thomas-EMF-dependent inhibition of cell proliferation. These experiments were expanded to show that exposure to Thomas-EMF inhibited proliferation of three malignant (MDA-MB-231 (breast), MCF-7 (breast), and Hela (cervical)) cell lines but not of three non-malignant (HBL-100 (breast), HEK293T (human embryonic kidney), and HSG (human salivary gland)) cell lines. Our results also showed that exposure to Thomas-EMF changed the levels of cAMP in the malignant cell lines (MDA-MB-231 and MCF-7), although there were no significant changes in cAMP levels in the non-malignant cell line (HBL-100). Our results show that exposure to Thomas-EMF caused a significant Ca 2+ influx in B16-BL6 cells when compared to sham-treated controls. Pre-treatment with the L-type Ca2+ inhibitors Fendiline, Nifedipine, or Verapamil did not have significant effects on the ability of Thomas-EMF to induce Ca2+ influx. However, pre-treatment with the T-type Ca2+ inhibitors Bepridil or Mibefradil significantly impaired the ability of Thomas-EMF to induce Ca2+ influx in BI6-BL6 cells. Numerous studies have shown differential expression of calcium channels (Ca2+) in malignant versus non-malignant cell lines. Finally, experiments were performed to assess the ability of exposure to Thomas-EMF to inhibit BI6-BL6 cell growth 'in vivo'. Syngeneic C57b mice were implanted with 106 BI6-BL6 melanoma cells and exposed to Thomas-EMF for 3 hours/day, for 17 to 21 days, and tumour growth measured. Results show that exposure to Thomas-EMF caused a significant reduction in tumour size (p <0.05) when compared to the sham-treated controls. Interestingly, there were no significant differences in tumour weight between Thomas-EMF and sham-treated controls. Gross tumour morphology differed between the sham- and Thomas-EMF-treated groups and this observation suggests that exposure to Thomas-EMF promoted an influx of immune cells and tumour necrosis. These results strengthen the idea that EMF effects are dependent upon their specific temporal patterns. Exposure of BI6-BL6 (and some other) malignant cells to Thomas-EMF was able to promote Ca2+ influx, activate cAMP and ERK signal transduction pathways, to inhibit cell growth ' in vitro', and tumour growth 'in vivo', but did not alter growth of non-malignant cells. This suggests that the specific Thomas-EMF pattern can selectively inhibit the growth of malignant cells and may provide a valuable tool for the treatment of cancer.
ISBN
9780494718919
0494718919