Experimental evidence for 60 Hz magnetic fields operating through the signal transduction cascade. Effects on calcium influx and c-MYC mRNA induction.

We tested the hypothesis that early alterations in calcium influx induced by an imposed 60 Hz magnetic field are propagated down the signal transduction (ST) cascade to alter c-MYC mRNa induction. To test this we measured both ST parameters in the same cells following 60 Hz magnetic field exposures in a specialized annular ring device (220 G (22 mT), 1.7 mV/cm maximal E(induced), 37 degrees C, 60 min). Ca2+ influx is a very early ST marker that precedes the specific induction of mRNA transcripts for the proto-oncogene c-MYC, an immediate early response gene. In three experiments influx of 45Ca2+ in the absence of mitogen was similar to that in cells treated with suboptimal levels of Con-A (1 micrograms/ml). However, calcium influx was elevated 1.5-fold when lymphocytes were exposed to Con-A plus magnetic fields; this co-stimulatory effect is consistent with previous reports from our laboratory [FEBS Lett. 301 (1992) 53-59; FEBS Lett. 271 (1990) 157-160; Ann. N.Y. Acad. Sci. 649 (1992) 74-95]. The level of c-MYC mRNA transcript copies in non-activated cells and in suboptimally-activated cells was also similar, which is consistent with the above calcium influx findings. Significantly, lymphocytes exposed to the combination of magnetic fields plus suboptimal Con-A responded with an approximate 3.0-fold increase in band intensity of c-MYC mRNA transcripts. Importantly, transcripts for the housekeeping gene GAPDH were not influenced by mitogen or magnetic fields. We also observed that lymphocytes that failed to exhibit increased calcium influx in response to magnetic fields plus Con-A, also failed to exhibit an increase in total copies of c-MYC mRNA. Thus, calcium influx and c-MYC mRNA expression, which are sequentially linked via the signal transduction cascade in contrast to GAPDH, were both increased by magnetic fields. These findings support the above ST hypothesis and provide experimental evidence for a general biological framework for understanding magnetic field interactions with the cell through signal transduction. In addition, these findings indicate that magnetic fields can act as a co-stimulus at suboptimal levels of mitogen; pronounced physiological changes in lymphocytes such as calcium influx and c-MYC mRNA induction were not triggered by a weak mitogenic signal unless accompanied by a magnetic field. Magnetic fields, thus, have the ability to potentiate or amplify cell signaling.

ELF magnetic fields, breast cancer, and melatonin: 60 Hz fields block melatonin's oncostatic action on ER+ breast cancer cell proliferation.

In this study we investigated whether a 60 Hz magnetic field can act at the cellular level to influence the growth of human estrogen-dependent breast cancer cells. Our experimental design assessed cell proliferation of a human breast cancer cell line, MCF-7, in the absence or the presence of melatonin which inhibits growth at a physiological concentration of 10(-9) M. In three experiments, continuous exposure to average sinusoidal 60 Hz magnetic fields of 1.90 +/- 0.01, 2.40 +/- 0.70, and 2.53 +/- 0.50 mG, or simultaneous exposure in matched incubators to average 60 Hz magnetic fields of 10.4 +/- 2.12, 11.95 +/- 2.73, and 11.95 +/- 3.28 mG, respectively, had no effect on cell proliferation in the absence of melatonin. When MCF-7 cells were cultured in the presence of 10(-9) M melatonin, an 18% inhibition of growth was observed for cells in a 2.40 +/- 0.70 mG field. This effect was blocked by a 60 Hz magnetic field of 11.95 +/- 2.75 mG. In a second experiment, a 27% inhibition of MCF-7 cell growth was observed for cells in a 2.53 +/- 0.50 mG magnetic field, and this was blocked by a 60 Hz magnetic field of 11.95 +/- 3.28 mG. These results provide the first evidence that ELF frequency magnetic fields can act at the cellular levels to enhance breast cancer cell proliferation by blocking melatonin's natural oncostatic action. In addition, there appears to be a dose threshold between 2 and 12 mG. The mechanism(s) of action is unknown and may involve modulation of signal transduction events associated with melatonin's regulation of cell growth.