Regulation of c-fos is affected by electromagnetic fields

The goal of the present study was to determine if regulatory regions of the c-fos gene were responsive to electromagnetic field exposure. The research design used transfected cells to increase the sensitivity of assays designed to identify changes following exposure. HeLa cells were transiently transfected with plasmids containing upstream regulating regions of c-fos up to -700 base pairs, coupled with the prokaryotic reporter gene CAT. Cells were exposed to an environmentally relevant EMF of 60 Hz at 60 mG_rms. CAT expression above control levels in transfected cells (region +42 to -700 bp) was observed following 5 min exposure to the electromagnetic field, with a peak at 20 min. The expression was at basal levels following 40 min exposure. Deletion analysis of upstream DNA narrowed the responsive region to 138 base pairs from -363 to -225, which contains the SRE/AP-1 sites. © 1996 Wiley-Liss, Inc.     

Magnetic field exposure enhances mRNA expression of σ32 in E. coli

The mechanism of interaction between weak electromagnetic fields and cells is not understood. As a result, the health effect(s) induced by exposure to these fields remains unclear. In addition to questions relating to the site of initial magnetic field (MF) interactions, the nature of the cell's response to these perturbations is also unclear. We examined the hypothesis that the cells respond to MFs in a manner similar to other environmental stressors such as heat. Using the bacterium Escherichia coli, we examined the mRNA levels of σ³², a protein that interacts with RNA polymerase to help it recognize a variety of stress promoters in the cell. Our data show that the intracellular level of σ³² mRNA is enhanced following a 15-min exposure to a 60 Hz, 1.1 mT magnetic field. J. Cell. Biochem. 68:1–7, 1998. © 1998 Wiley-Liss, Inc.     

Analysis of the effect of a 60 Hz AC field on histamine release by rat peritoneal mast cells

Reports have indicated effects of electromagnetic fields on inflammatory processes in vivo. To begin a systematic approach toward separating and examining the many components of such responses, we created and tested a temperature-controlled device to develop 5 mT 60 Hz magnetic fields for studies of the effects of fields on mast cells, a key component in acute inflammatory responses. Such fields have been reported to modulate cell activity, including changes in membrane function, in various systems. The magnetic field was generated using a solenoid and calibrated with an induction probe. Tests of mast cell function were determined by histamine release response to stimulation by compound 48/80, using both an “expose then test” and a “test during exposure” protocol. Aliquots not treated with 48/80 were used to evaluate field treatment effects on spontaneous histamine release. Freshly harvested rat peritoneal mast cells were exposed to the magnetic field for periods of 30 min to 2 h at 37 °C. They showed no significant degranulation during treatment, nor did they show reduced sensitivity to the degranulating agent 48/80. These observations are consistent with a model in which such processes are exclusively reflexive by the cells using field-independent membrane systems. This observation is very useful and was needed before examining longer term exposures in which gene expression in the cells might be influenced; this is the first such report of in vitro exposure of purified mast cells under these conditions and will further the study of the effects of electromagnetic fields on cell types active in acute inflammation. Bioelectromagnetics 19:192–198, 1998. © 1998 Wiley-Liss, Inc.     

Electric fields induced in chicken eggs by 60-Hz magnetic fields and the dosimetric importance of biological membranes.

Chicken eggs are convenient models for observing the effects of inhomogeneities and variations, such as those found in biological membranes and in cellular conductivities, on the distribution of internal electric fields as induced by exposure to magnetic fields. The vitelline membrane separates the yolk, which has a conductivity of 0.26 S/m, from the white, which has a conductivity of 0.85 S/m. A miniaturized probe with 2.4-mm resolution was used to measure induced fields in eggs placed in a uniform, 1-mT magnetic field at 60 Hz. The E fields induced in eggs with homogenized contents agreed with expectations based on simple theory. Results were similar to intact eggs unless the probe moved the yolk off-center, which greatly perturbed the induced fields. A more reproducible arrangement, which consisted of saline-agar filled dishes with a hole cut for test samples, was developed to enhance definition of electrical parameters. With this test system, the vitelline membrane was found to be responsible for most of the perturbation of the induced field, because it electrically isolates the yolk from the surrounding white. From a theoretical viewpoint, this dosimetry for the macroscopic egg yolk is analogous to the interaction of fields with microscopic cells. These findings may have important implications for research on biological effects of ELF electromagnetic fields, especially for studies of avian embryonic development.     

Epilepsy and electromagnetic fields: effects of simulated atmospherics and 100-Hz magnetic fields on audiogenic seizure in rats

In order to study the possible association between epileptic seizures and natural electromagnetic fields, 32 female audiogenic seizure (AGS)-susceptible rats were exposed to simulated 10 kHz and 28 kHz atmospherics and to a sinusoidally oscillating magnetic field with a frequency of 100 Hz and field strength of 1 A/m. After the electromagnetic exposure, seizures were induced in the rats with a sound stimulus. The severity of the seizure was determined on an ordinal scale, the audiogenic response score (ARS). The time from the beginning of the sound stimulus to the onset of the seizure (seizure latency) and the duration of the convulsion was measured. No differences from the control experiments were found in the experiments with simulated atmospherics, but the 100 Hz magnetic field increased the seizure latency by about 13% (P<0.02). The results do not support the hypothesis that natural atmospheric electromagnetic signals could affect the onset of epileptic seizures, but they suggest that AGS-susceptible rats may be a useful model for studying the biological effects of electromagnetic fields.     

Static and extremely low frequency electromagnetic field exposure: Reported effects on the circadian production of melatonin

The circadian rhythm of melatonin production (high melatonin levels at night and low during the day) in the mammalian pineal gland is modified by visible portions of the electromagnetic spectrum, i.e., light, and reportedly by extremely low frequency (ELF) electromagnetic fields as well as by static magnetic field exposure. Both light and non-visible electromagnetic field exposure at night depress the conversion of serotonin (5HT) to melatonin within the pineal gland. Several reports over the last decade showed that the chronic exposure of rats to a 60 Hz electric field, over a range of field strengths, severely attenuated the nighttime rise in pineal melatonin production; however, more recent studies have not confirmed this initial observation. Sinusoidal magnetic field exposure also has been shown to interfere with the nocturnal melatonin forming ability of the pineal gland although the number of studies using these field exposures is small. On the other hand, static magnetic fields have been repeatedly shown to perturb the circadian melatonin rhythm. The field strengths in these studies were almost always in the geomagnetic range (0.2 to 0.7 Gauss or 20 to 70 μtesla) and most often the experimental animals were subjected either to a partial rotation or to a total inversion of the horizontal component of the geomagnetic field. These experiments showed that several parameters in the indole cascade in the pineal gland are modified by these field exposures; thus, pineal cyclic AMP levels, N-acetyltransferase (NAT) activity (the rate limiting enzyme in pineal melatonin production), hydroxyindole-O-methyltransferase (HIOMT) activity (the melatonin forming enzyme), and pineal and blood melatonin concentrations were depressed in various studies. Likewise, increases in pineal levels of 5HT and 5-hydroxyindole acetic acid (5HIAA) were also seen in these glands; these increases are consistent with a depressed melatonin synthesis. The mechanisms whereby non-visible electromagnetic fields influence the melatonin forming ability of the pineal gland remain unknown; however, the retinas in particular have been theorized to serve as magnetoreceptors with the altered melatonin cycle being a consequence of a disturbance in the neural biological clock, i.e., the suprachiasmatic nuclei (SCN) of the hypothalamus, which generates the circadian melatonin rhythm. The disturbances in pineal melatonin production induced by either light exposure or non-visible electromagnetic field exposure at night appear to be the same but whether the underlying mechanisms are similar remains unknown.     

Magnetic fields generated by an induction heating (IH) cook top do not cause genotoxicity in vitro

The use of induction heater (IH) cook tops in homes has become widespread, especially in Japan, but there are concerns about the safety of intermediate frequency (IF) electromagnetic fields associated with these cooking appliances. Since the cellular genotoxicity of IF magnetic fields has not been examined in cultured cells, we examined the effects of these fields at a magnetic flux density of 532 +/- 20 microT at 23 kHz, using an exposure unit with a built-in CO2 incubator. Exposure to the IF magnetic field at 532 microT for 2 h did not affect the growth of CHO-K1 cells and caused no mutagenic effects in bacterial mutation assays. Exposure to the IF magnetic field for 2 h induced neither single nor double DNA strand breaks in comet assays, and caused no significant change in the mutation frequency at the HPRT locus compared to sham exposure. The magnetic field used in this study is more than 80 times higher than the level recommended as safe in the International Commission on Non-ionizing Radiation Protection (ICNIRP) guidelines. From these results, we suggest that exposure to an IF magnetic field for 2 h does not cause cellular genotoxicity in bacteria and in Chinese hamster cells. However, the possibility of effects on other cellular functions remains, and further studies on the cellular effects of IF magnetic fields are required.     

Subcellular mechanisms of the action of weak extra-low frequency electromagnetic fields on the cerebral cortex

Electron microscopic examinations of the cerebral cortex in rabbits and rats after exposure to weak extra-low electromagnetic fields has detected ultrastructural changes whose degree in different nerve tissue elements was dependent on the duration of irradiation. Single exposure to weak extra-low electromagnetic field resulted only in the glial response of the neocortex, while multiple exposure resulted alternately in the response of glial cells or neuronal bodies. Three days after a single exposure and within 15 days after multiple exposure to electromagnetic field a complete repair of the nervous tissue was observed. No destructive or pathological alterations have been found which suggests the functional character of the reactions induced. Neuro-morphological alterations are of a similar character when induced by weak extra-low electromagnetic fields or other biophysical effects which points to common subcellular mechanisms of nonspecific adaptive reactions.     

Reduced induction of c-fos but not of c-myc expressions in a nontumorigenic revertant R1 of EJ-ras-transformed NIH/3T3 cells treated with 12-O-tetradecanoylphorbol-13-acetate (TPA)

It has been reported that both c-fos and c-myc mRNAs are induced in NIH/3T3 cells after 12-O-tetradecanoylphorbol-13-acetate (TPA) treatment. We have studied the effect of TPA on the expression of c-fos and c-myc in EJ-ras-transformed NIH/3T3 and its nontumorigenic flat revertant R1 cells. Although TPA treatment induces c-myc mRNA, as in the case of NIH/3T3 cells, the induced level of c-fos mRNA is greatly reduced not only in slow-growing EJ-ras-transformed NIH/3T3 but also in quiescent R1 cells. In addition, serum-induced c-fos expression is also reduced in EJ-ras-transformed NIH/3T3 and R1 cells. These observations suggest that the pathway from TPA to c-fos gene is different from that to c-myc gene and that the former pathway is down-regulated in association not with the transformed phenotype, but with EJ-ras expression, and it is possible that this reduced induction of c-fos is not specific to TPA.