• Bone healing and other therapeutic applications. The clinical application of electric-and magnetic-field exposure at relatively high field strengths for bone healing is of limited but real benefit. Additional research could clarify the molecular mechanisms involved. Better understanding of these mechanisms might allow design of electric and magnetic-field treatments for other conditions, such as osteoporosis, and lend insight into understanding possible interactive mechanisms that might result in adverse health effects of such exposure.

  • Characterization of the dose-response relationship for in vitro effects. Reproducible effects have been documented in cultured cells for electric-and magnetic-field-induced changes in calcium flux and gene expression, but only at very high magnetic-field flux densities or high electric-field strengths. When a robust effect can be observed in such studies, special effort should be made to define the change in effect as a function of the strength of the applied fields. The shape of the relationship between the field strength and the biologic effect must be established precisely to permit extrapolation and use in predicting effects at lower strengths. Exposure-response studies could also be extended to characterize the effects of the frequency of the applied fields and the effects of transient currents on the biologic response.

  • Signal-transduction events. Further replication and validation studies could be carried out to investigate the apparent effects of magnetic fields on signal-transduction events, such as Ca2+ flux, protein-kinase cascades, and membrane-receptor activities. These pathways are important in both normal and neoplastic cell proliferation and differentiation, and possible effects of magnetic fields on these pathways might be related to the observed copromotion activity of exposure to magnetic fields in animal studies.

  • Gene expression. Previously reported effects of magnetic fields on gene expression (e.g., changes in differentiation markers of bone cells and changes in signal-transduction effects) could be investigated further. Studies of putative direct effects of magnetic fields on transcriptional events could have low priority.

  • Biophysical mechanisms. Research could be directed at plausible biophysical mechanisms to explain the observed in vitro and in vivo effects at relatively high magnetic-field strengths (e.g., 1-10 G). The possible role of transient currents on electric-and magnetic-field-induced effects also could be examined.

  • Cocarcinogenesis. There are unreplicated data in animal studies that reported increased tumor incidence when magnetic fields were applied in combination with chemical carcinogens. Those data require replication, and if replication reinforces the reported positive results, these observations should be pursued in detailed experiments. Such experiments should focus on the dose-response relationships of magnetic-field exposures, the interacting exposures, and the temporal relationships between the different exposure conditions. Positive results could be tested in different cell or animal systems to determine whether the response is peculiar to specific biologic systems.

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