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 maximal E induced, 37°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 ). 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.

We have previously reported that environmental‐level magnetic fields (1.2 μT [12 milligauss], 60 Hz) block the growth inhibition of the hormone melatonin (10−9 M) on MCF‐7 human breast cancer cells in vitro. We now report that the same 1.2 μT, 60 Hz magnetic fields significantly block the growth inhibitory action of pharmacological levels of tamoxifen (10−7 M). In biophysical studies we have taken advantage of Faraday's Law of Current Induction and tested whether the 1.2 μT magnetic field or the associated induced electric field is responsible for this field effect on melatonin and tamoxifen. We observe that the magnetic field component is associated with the field blocking effect on melatonin and tamoxifen function. To our knowledge the tamoxifen studies represent the first experimental evidence for an environmental‐level magnetic field modification of drug interaction with human breast cancer cells. Together, these findings provide support to the theory that environmental‐level magnetic fields can act to modify the action of a drug or hormone on regulation of cell proliferation. Melatonin and tamoxifen may act through different biological pathways to down‐regulate cell growth, and further studies are required to identify a specific biological site of interaction for the 1.2 μT magnetic field. Bioelectromagnetics 18:555–562, 1997. Published 1997 Wiley‐Liss, Inc.

One critical biophysical feature of environmental-level magnetic field (MF) interactions with biological systems is the time-scale of interaction. A recently proposed fast/slow hypothesis states that a fast mechanism can only sense the instantaneous absolute value of the MF, and that a slow mechanism is potentially capable of sensing features such as frequency and relative orientation and magnitude of the field components. Here we applied the fast/slow hypothesis to a breast cancer model system: A 1.2 microT (rms), 60-Hz field inhibits tamoxifen's (TAM's) cytostatic action in MCF-7 cells via a MF interaction. We measured the growth of MCF-7 cells treated with TAM over 7 d, within different MFs: a sinusoidal, 60-Hz, 0.2-microT(rms) field; a sinusoidal, 60-Hz, 1.2-microT(rms) field; and a full-wave rectified version of the 1.2-microT(rms) sinusoidal field. A fast mechanism should not be able to distinguish between the latter two exposures. We observe that the rectified 1.2-microT field does not inhibit TAM's action, but that the 1.2-microT sinusoidal field does. Therefore, the 1.2-microT MF inhibition of TAM's cytostatic action operates via a relatively slow mechanism, and we predict that there exists a biologically dynamic complex capable of sensing a 1.2-microT, 60-Hz sinusoidal MF with an intrinsic time-scale of 17 ms or longer, the period of the 60-Hz applied field.