Do cocarcinogenic effects of ELF electromagnetic fields require repeated long‐term interaction with carcinogens? Characteristics of positive studies using the DMBA breast cancer model in rats

The carcinogenic or cocarcinogenic potential of extremely low frequency (ELF; 50 or 60 Hz) magnetic fields (MFs) has been evaluated worldwide in diverse animal model systems. Though most results have been negative, weakly positive or equivocal results have been reported in several cancer models, including the rat DMBA (7,12-dimethylbenz[a]anthracene) model of mammary cancer. Based on the experimental conditions used in studies in which cocarcinogenic effects of ELF MF were found, it was recently proposed that MF exposure may potentiate the effects of known carcinogens only when the animals are exposed to both MF and carcinogen during an extended period of tumor development, i.e., when the carcinogen is given repeatedly during MF exposure. This review summarizes a series of experiments from our group, showing cocarcinogenic MF effects in the DMBA breast cancer model in rats, to test whether the above proposal is confirmed by existing data. Flux densities of 50 or 100 microT significantly increased the growth of mammary tumors, independent of whether DMBA was given in a single administration or repeatedly over a prolonged period. Thus, these data do not substantiate the hypothesis requiring repeated doses of DMBA during MF exposure. Instead, several other aspects of study design and experimental factors are identified that seem to be critical for the detection of cocarcinogenic effects of MF exposure in the rat DMBA mammary cancer model. These include the rat subline used, the dose of DMBA, the duration of MF exposure, the flux density, the background (sham control) tumor incidence, and the location of mammary tumors in the mammary gland complex. These and other experimental aspects may explain why some laboratories did not detect cocarcinogenic MF effects in the DMBA model. We hope that direct comparison of MF bioeffects in different rat sublines and further evaluation of other experimental differences between studies on MF exposure in the DMBA model will eventually determine which genetic and environmental factors are critical for potential carcinogenic or cocarcinogenic effects of ELF MF exposure.     

Exposure of rats to a 50-Hz, 100 muTesla magnetic field does not affect the ex vivo production of interleukins by activated T or B lymphocytes.

Two separate, independent experiments were conducted to evaluate the effects of exposure of rats to a 50-Hz linearly polarized, 100 microT magnetic field (MF) on the ex vivo production of interleukins (ILs) by mitogen-stimulated splenic lymphocytes. IL-1 and IL-2 were determined by proliferation assays, using IL-dependent murine T cell lines. In the first experiment, female Sprague-Dawley rats were treated with 7,12-dimethylbenz[a]anthracene (DMBA] at a dose of 20 mg per rat (four weekly gavage doses of 5 mg), and were either MF-exposed or sham-exposed for 14 weeks. This experimental protocol has previously been shown to result in a significant increase in breast cancer growth in response to MF exposure. Furthermore, MF exposure at 50-100 microT for 3 months was recently found to induce a suppressed ex vivo proliferation of splenic T cells in response to mitogen stimulation, which could be a result of reduced IL production of spleen lymphocytes. However, the present experiments failed to demonstrate any significant difference between MF- and sham-exposed groups in production of IL-1 by mitogen-activated splenic B cells. In a second experiment, shorter MF exposure periods were studied with respect to IL production from mitogen-stimulated B and T cells. Groups of rats were MF- or sham-exposed for 1 day, 1 week, or 2 weeks, followed by preparation and activation of spleen lymphocytes. No significant difference in IL-1 or IL-2 production from stimulated B or T cells was seen. The data indicate that in vivo MF exposure of rats does not affect the ex vivo IL production of B or T lymphocytes, suggesting that the recently reported changes in T cell proliferation in response to MF exposure may not be mediated via alterations in B or T cell IL production.     

Lymphocyte subset analyses in blood, spleen and lymph nodes of female Sprague-Dawley rats after short or prolonged exposure to a 50 Hz 100-microT magnetic field.

Based primarily on the results of in vitro studies, it has been suggested that power-line (50 or 60 Hz) magnetic fields (MFs) may reduce immune function, which could lower resistance to infection or cancer. This study was conducted to evaluate the influence of acute and chronic in vivo exposure to a linearly polarized 50 Hz MF on immune function in female Sprague-Dawley rats. Groups of rats were exposed continuously to the MF at a flux density of 100 microT for periods of 3 days, 14 days or 13 weeks. For each exposure period, one control group of rats was sham-exposed together with each MF-exposed group. Experimental end points included analyses of T-lymphocyte subsets as well as other immune cells involved in cell-mediated immune responses, i.e. natural killer (NK) cells, B lymphocytes, macrophages, and granulocytes in blood, spleen and mesenteric lymph nodes. In addition, immunohistochemical methods were used to detect proliferating and apoptotic cells in the various compartments of spleen tissue. The results obtained failed to demonstrate a significant effect of short or prolonged MF exposure on different types of leukocytes, including lymphocyte subsets. Furthermore, the experiments on the in vivo proliferation activity of lymphocytes and the extent of apoptosis in spleen samples did not indicate a difference between the MF-exposed and sham-exposed groups, indicating that MF exposure does not affect the mechanisms involved in the control of lymphocyte homeostasis. The lack of MF effects in the immune tests used in the present in vivo study makes it highly unlikely that MF exposure induces immunotoxicity, at least under the experimental conditions used. However, the data do not exclude the possibility that functional alterations in T-cell responses to mitogens and in NK cell activity as recently described for MF-exposed rodents may be one mechanism involved in the carcinogenic effects of MF exposure observed in some models of co-carcinogenesis.     

The Relative Permittivity Changes of EGF by 50 Hz MF Exposure Neither Affect the Interaction of EGF With EGFR Nor Its Biological Effects

The biophysical mechanism of magnetic fields (MFs) acting on living systems is not clear. Previous research showed that, similar to epidermal growth factor (EGF), MF exposure induced EGF receptor (EGFR) clustering and activated EGFR signaling. In this study, we investigated whether MF exposure induced the changes in physical characteristics of EGF and downstream effects of EGF and EGFR interaction. The phase-interrogation surface plasmon resonance (SPR) sensing analyses showed that 50 Hz MF exposure at 4.0 mT for 1 h induced reversible relative permittivity changes of EGF solution. However, compared with sham-exposed EGF solution, the MF-exposed EGF solution did not affect the binding of EGF to EGFR, nor the cell viability and EGFR clustering in human amniotic epithelial cells (FL cells). Our data suggest that cellular EGFR clustering response to MF exposure might not be a result of changes in relative permittivity of EGF in cell culture solution. Bioelectromagnetics. © 2020 Bioelectromagnetics Society     

Effects of 60 Hz magnetic field exposure on the pineal and hypothalamic-pituitary-gonadal axis in the Siberian hamster (Phodopus sungorus)

Experiments using the dwarf Siberian hamster Phodopus sungorus were carried out to determine possible neuroendocrine consequences of one-time and repeated exposures to 60 Hz magnetic fields (MF). Animals were maintained in either a short-light (SL, 8 h light:16 h dark) or long-light (LL, 16 h light:8 h dark) photoperiod. Acute (one-time, 15 min) exposure of male SL animals to a linearly polarized, horizontally oriented, 60 Hz MF (0.1 mT) gave rise to a statistically significant (P < .005) reduction in pineal melatonin content as determined 3 and 5 h after onset of darkness. In LL animals, acute exposure to 0.10 mT resulted in a significant decrease in pineal melatonin as measured 4 h after onset of darkness, whereas acute exposure to 50 microT showed no effect compared with sham exposure. In SL animals, an increase in norepinephrine was observed in the medial basal hypothalamus (including the suprachiasmatic nucleus) after acute exposure (P < .01). Daily MF exposure of SL animals to a combination of steady-state and on/off 60 Hz magnetic fields (intermittent exposure) at 0.1 mT for 1 h per day for 16 days was associated with a reduction in melatonin concentrations at 4 h after onset of darkness and an increase in blood prolactin concentrations (P < .05). Exposure of SL animals to a steady state 60 Hz MF for 3 h/day for 42 days resulted in a statistically significant reduction in body weight (ANOVA: P > .05), compared with sham-exposed SL animals. At 42 days, however, no significant changes in overnight melatonin or prolactin levels were detected. In both repeated exposure experiments, gonadal weights were lowest in the MF-exposed groups. This difference was statistically significant (P < .05) after 42 days of exposure. These data indicate that both one-time and repeated exposure to a 0.1 mT, 60 Hz MF can give rise to neuroendocrine responses in Phodopus.     

Rats can discriminate illuminance,but not magnetic fields,as a stimulus for learning a two-choice discrimination

In each of the two experiments, nine rats were trained for 64 trials (eight trials per day) to determine if they could acquire a two-choice discrimination based on a specified discriminative stimulus (S(D)). In one experiment, the S(D) was a change in ambient illumination, while in the second experiment the S(D) was a change in the combination of sinusoidal 60 Hz and static magnetic field (MF) and any cues attendant to energizing the coils that produced the MF exposure. The rats that had a change in illuminance as the S(D) learned the two-choice task easily, P <.001, whereas the rats having a change in MFs as the S(D) did not.     

Effect of magnetic fields on rodent monooxygenase enzymes

The effects of 50 Hz, 1.2 mT magnetic fields (MFs) were tested on hepatic monooxygenase enzymes of basal and β-naphthoflavone-phenobarbital-preinduced rats and mice. An inductive effect on cytochrome P-450 level and on some enzymatic cytochrome P-450-dependent activities was observed in basal mice after MF exposure. Enzymatic activities in preinduced mice and rats were reduced by MFs, the degree of reduction depending on the enzyme. A specific inhibitory effect was determined in some of the assayed activities and in the relative peculiar P-450 isoforms detected by Western blot analysis. © 1995 Wiley-Liss, Inc.     

Alterations in ornithine decarboxylase activity in the rat mammary gland after different periods of 50 Hz magnetic field exposure.

In a series of experiments with the chemical carcinogen DMBA (7, 12-dimethyl[a]anthracene), we recently found that exposure of female Sprague-Dawley rats in 50 Hz magnetic fields (MF) in the microtesla range significantly facilitates the development and growth of mammary tumors. One possible explanation for this finding would be enhanced proliferation of breast epithelial stem cells by MF exposure, thereby increasing the sensitivity of these cells to chemical carcinogens. In line with this possibility, we previously determined that 50 Hz, 50 microT MF exposure induces increases in ornithine decarboxylase (ODC), i.e., a key enzyme in cell proliferation, in the mammary gland of female Sprague-Dawley rats. In the present study, we examined the time course of this effect, by using different periods of exposure to a 50 Hz, 100 microT MF. Furthermore, we determined ODC in different mammary complexes of the rat mammary gland to evaluate whether differences in response to MF exist over the anterior-posterior extension of this organ. Exposure of young female Sprague-Dawley rats induced marked increases in ODC in the mammary gland that were similar to ODC increases seen in "positive control" experiments with the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA). However, this effect of MF critically depended on the duration of MF exposure, with no effect, or at least no consistent effect, for short (<1 week) or long (8 weeks and above) exposure periods, but a robust and reproducible enhancing effect on ODC activity after 2 weeks of exposure. Furthermore, we found that the effect of MF exposure depends on the part of the mammary complexes examined, the cranial thoracic (or cervical) complexes being particularly sensitive to ODC alterations in response to MF. This is in line with recent DMBA experiments of our group in which MF-induced increases in tumor development and growth were predominantly seen in this large cranial/cervical part of the mammary gland. The most likely explanation for the observed ODC changes after MF exposure is the "melatonin hypothesis," although other cellular and molecular effects of MF might be involved as well.     

The effect of 100 Hz magnetic field combined with X-ray on hepatoma-implanted mice

Our previous cellular experiments demonstrated that 100 Hz magnetic field (MF) was effective at enhancing apoptosis of liver cancer cells BEL‐7402 induced by X‐ray irradiation. This study was performed to further explore the possible synergism between 100 Hz MF and X‐ray in treatment of hepatoma‐implanted Balb/c mice. 100 Hz MF exposure with a mean flux density of 0.7 mT was performed inside an energized solenoid coil. Six MV X‐ray irradiation was generated using a linear accelerator. Tumor growth and survival of mice implanted with H22 cells were evaluated by measuring the tumor diameters and overall days of survival. Six groups treated with 100 Hz MF or X‐ray alone or a combination of MF and X‐ray were examined. Furthermore, the effects of different numbers of MF exposure periods on tumor growth and mice survival were examined when combined with 4 Gy X‐ray. Data referring to overall survival days and tumor diameters of the above groups were compared using log‐rank test and Student's t‐test. Our results showed that five periods of combined 100 Hz MFs and 4 Gy X‐ray could significantly extend the overall days of survival and reduce the tumor size compared to MF or X‐ray alone. Also, a greater number of 100 Hz MF exposure periods could further improve the survival and inhibit tumor growth in hepatoma‐implanted mice when combined with 4 Gy X‐ray. In conclusion, these findings suggested that 100 Hz MF could possibly synergize with 4 Gy X‐ray in terms of survival improvement and tumor inhibition in hepatoma‐implanted mice. Bioelectromagnetics 32:322–324, 2011. © 2011 Wiley‐Liss, Inc.     

Intracellular calcium activity in isolated bovine adrenal chromaffin cells in the presence and absence of 60 Hz magnetic fields

This study examined whether 60 Hz magnetic field (MF) exposure alters intracellular calcium levels ([Ca(2+)](i)) in isolated bovine adrenal chromaffin cells, a classic model of neural responses. [Ca(2+)](i) was monitored by fluorescence video imaging of cells loaded with the calcium indicator fluo-4 during exposures to magnetic flux densities of 0.01, 0.1, 1.0, 1.4, or 2.0 mT. MFs generated by Helmholtz coils constructed from bifilar wire allowed both 60 Hz field and sham exposures. Following a 5 min monitoring period to establish baseline patterns, cells were subjected for 10 min to a 60 Hz MF, sham field or no field. Reference calcium responses and assessment of cell excitability were obtained by the sequential addition of the nicotinic cholinergic receptor agonist dimethylphenylpiperazinium (DMPP) and a depolarizing concentration of KCl. Throughout an 8 day culture period, cells exhibited spontaneous fluctuations in [Ca(2+)](i). Comparisons of the number of cells exhibiting transients, the number and types of calcium transients, as well as the time during monitoring when transients occurred showed no significant differences between MF exposed cells and either sham exposed or nonexposed cells. With respect to the percentage of cells responding to DMPP, differences between 1 and 2 mT exposed cells and both nonexposed and sham exposed cells reached statistical significance during the first day in culture. No statistically significant differences were observed for responses to KCl. In summary, our data indicate that [Ca(2+)](i) in chromaffin cells is unaffected by the specific 60 Hz MF intensities used in this study. On the other hand, plasma membrane nicotinic receptors may be affected in a manner that is important for ligand-receptor interactions.     

No influence of magnetic fields on cell cycle progression using conditions relevant for patients during MRI

The purpose of this study was to examine whether exposure to magnetic fields (MFs) relevant for magnetic resonance imaging (MRI) in clinical routine influences cell cycle progression in two tumor cell lines in vitro. HL60 and EA2 cells were exposed to four types of MFs: (i) static MF of 1.5 and 7.05 T, (ii) extremely low frequency magnetic gradient fields (ELFMGFs) with +/- 10 mT/m and 100 Hz, as well as +/- 100 mT/m and 100 Hz, (iii) pulsed high frequency MF in the radiofrequency (RF) range (63.6 MHz, 5.8 microT), and (iv) a combination of (i-iii). Exposure periods ranged from 1 to 24 h. Cell cycle distribution (G(0)/G(1), S, and G(2)/M phases) was analyzed by flow cytometry. Cell cycle analysis did not reveal differences between the exposed and the control cells. As expected, positive controls with irradiated (8 Gy) HL60 and EA2 cells showed a strong G(2)/M arrest. Using conditions that are relevant for patients during MRI, no influence of MFs on cell cycle progression was observed in these cell lines. Care was taken to control secondary parameters of influence, such as vibration by the MR scanner or temperature to avoid false positive results.     

Influence of weak static and 50 Hz magnetic fields on the redox activity of cytochrome-C oxidase

The effects of static and 50 Hz magnetic fields on cytochrome-C oxidase activity were investigated in vitro by strictly controlled, simultaneous polarographic measurements of the enzyme's high- and low-affinity redox reaction. Cytochrome-C oxidase was isolated from beef heart. Control experiments were carried out in the ambient geomagnetic and 50 Hz magnetic fields at respective flux densities of 45 and 1.8 μT. The experimentally applied fields, static and time-varying, were generated by Helmholtz coils at flux densities between 50 μT and 100 mT. Exposures were timed to act either on the combined enzyme-substrate interchange or directly on the enzyme's electron and proton translo-cations. Significant changes as high as 90% of the overall cytochrome-C oxidase activity resulted during exposure (1) to a static magnetic field at 300 μT or 10 mT in the high-affinity range, and (2) to a 50 Hz magnetic field at 10 or 50 mT in the low-affinity range. No changes were observed at other flux densities. After exposure to a change-inducing, static or time-varying field, normal activity returned. © 1993 Wiley-Liss. Inc.     

Static magnetic fields affect calcium fluxes and inhibit stress-induced apoptosis in human glioblastoma cells

BACKGROUND: Epidemiologic data revealed increased brain tumor incidence in workers exposed to magnetic fields (MFs), raising concerns about the possible link between MF exposure and cancer. However, MFs seem to be neither mutagenic nor tumorigenic. The mechanism of their tumorigenic effect has not been elucidated. METHODS: To evaluate the interference of MFs with physical (heat shock, HS) and chemical (etoposide, VP16) induced apoptoses, respectively, we exposed a human glioblastoma primary culture to 6 mT static MF. We investigated cytosolic Ca(2+) ([Ca(2+)](i)) fluxes and extent of apoptosis as key endpoints. The effect of MFs on HS- and VP16-induced apoptoses in primary glioblastoma cultures from four patients was also tested. RESULTS: Static MFs increased the [Ca(2+)](i) from a basal value of 124 +/- 4 nM to 233 +/- 43 nM (P < 0.05). MF exposure dramatically reduced the extent of HS- and VP16-induced apoptoses in all four glioblastoma primary cultures analyzed by 56% (range, 28-87%) and 44% (range, 38-48%), respectively. However, MF alone did not exert any apoptogenic activity. Differences were observed across the four cultures with regard to apoptotic induction by HS and VP16 and to MF apoptotic reduction, with an individual variability with regard to apoptotic sensitivity. CONCLUSION: The ability of static MFs to reduce the extent of damage-induced apoptosis in glioblastoma cells might allow the survival of damaged and possibly mutated cells.     

Complex effects of long-term 50 Hz magnetic field exposure in vivo on immune functions in female Sprague-Dawley rats depend on duration of exposure

In previous studies we have demonstrated that 50 Hz, 100 μT magnetic field (MF) exposure of female Sprague-Dawley rats for 13 weeks significantly enhances the development and growth of mammary tumors in a breast cancer model. The present study was designed to test the hypothesis that, at least in part, the tumor (co)promoting effect of MF exposure is due to MF effects on the immune surveillance system, which is of critical importance in protecting an organism against the development and growth of tumors. For this purpose, female Sprague-Dawley rats of the same age as in the mammary tumor experiments were continuously exposed for different periods (2, 4, 8, and 13 weeks) to a 50 Hz, 100 μT MF. Control groups were sham-exposed simultaneously. Following the different exposure periods, splenic lymphocytes were cultured and the proliferative responses to the T-cell-selective mitogen concanavalin A (Con A) and the B-cell-selective pokeweed mitogen (PWM) were determined. Furthermore, the production of interleukin-1 (IL-1) was determined in the splenocyte cultures. The mitogenic responsiveness of T cells was markedly enhanced after 2 weeks of MF exposure, suggesting a co-mitogenic action of MF. A significant, but less marked increase in T-cell mitogenesis was seen after 4 weeks of MF exposure, whereas no difference from sham controls was determined after 8 weeks, indicating adaptation or tolerance to this effect of MF exposure. Following 13 weeks of MF exposure, a significant decrease in the mitogenic responsiveness of lymphocytes to Con A was obtained. This triphasic alteration in T-cell function (i.e., activation, tolerance, and suppression) during prolonged MF exposure resembles alterations observed during chronic administration of mild stressors, substantiating the hypothesis that cells respond to MF in the same way as they do to other environmental stresses. In contrast to T cells, the mitogenic responsiveness of B cells and IL-1 production of PWM-stimulated cells were not altered during MF exposure. The data demonstrate that MF in vivo exposure of female rats induces complex effects on the mitogenic responsiveness of T cells, which may lead to impaired immune surveillance after long-term exposure. Bioelectromagnetics 19:259–270, 1998. © 1998 Wiley-Liss, Inc.     

Protein kinase C activity following exposure to magnetic field and phorbol ester

We examined the separate and combined effects of 60 Hz sinusoidal magnetic fields (MFs) and a phorbol ester on protein kinase C (PKC) activity in HL60 cells. No enhancement in PKC activity was observed when a cell culture was exposed to a 1.1 mT (rms) MF alone or to a combination of MF and 2 μM phorbol 12-myristate 13-acetate (PMA) for 1 h. In a second set of experiments, cells were preexposed to a less than optimal concentration of PMA (50 nM) for 45 min, followed by a 15 min exposure to both PMA and MF. The data showed a greater decrease in cytosolic PKC activity and a larger increase in membrane activity than was induced by either 1 h PMA treatment alone or PMA and sham MF exposure. One logical conclusion from these data is that MFs may be acting in a synergistic manner on a pathway that has already been activated. Therefore, we suggest that MFs, rather than producing biological effects by a new pathway or mechanism of interaction, exert their effect(s) by interacting with already functioning reactions or pathways. If correct, the question of an MF's mechanism of interaction refocuses on how weak fields might enhance or depress a molecular reaction in progress, rather than on finding a new transduction pathway. Bioelectromagnetics 19:469–476, 1998. © 1998 Wiley-Liss, Inc.     

DNA damage in rat lymphocytes treated in vitro with iron cations and exposed to 7 mT magnetic fields (static or 50 Hz)

The present study was undertaken to verify a hypothesis that exposure of the cells to static or 50 Hz magnetic fields (MF) and simultaneous treatment with a known oxidant, ferrous chloride, may affect the oxidative deterioration of DNA molecules.The comet assay was chosen for the assessment of DNA damage. The experiments were performed on isolated rat lymphocytes incubated for 3h in Helmholtz coils at 7 mT static or 50 Hz MF. During MF exposure, part of the cell samples were incubated with 0.01 microM H(2)O(2) and another one with 10 microg/ml FeCl(2,) the rest serving as controls.Lymphocyte exposure to MF at 7 mT did not increase the number of cells with DNA damage in the comet assay. Incubation of lymphocytes with 10 microg/ml FeCl(2) did not produce a detectable damage of DNA either. However, when the FeCl(2)-incubated lymphocytes were simultaneously exposed to 7 mT MF, the number of damaged cells was significantly increased and reached about 20% for static MF and 15% for power frequency MF. In the control samples about 97% of the cells did not have any DNA damage.It is not possible at present to offer a reasonable explanation for the findings of this investigation - the high increase in the number of lymphocytes showing symptoms of DNA damage in the comet assay, following simultaneous exposure to the combination of two non-cytotoxic factors -10 microg/ml FeCl(2) and 7 mT MF. In view of the obtained results we can only hypothesise that under the influence of simultaneous exposure to FeCl(2) and static or 50 Hz MF, the number of reactive oxygen species generated by iron cations may increase substantially. Further studies will be necessary to confirm this hypothesis and define the biological significance of the observed effect.     

Effect of weak combined static and extremely low‐frequency alternating magnetic fields on tumor growth in mice inoculated with the Ehrlich ascites carcinoma

It has been shown that the ultralow‐frequency extremely weak alternating component of combined magnetic fields (MFs) exhibits a marked antitumor activity. The parameters of this component have been found (frequency 1, 4.4, 16.5 Hz or the sum of these frequencies; intensity 300, 100, 150–300 nT, respectively) at which this MF in combination with a collinear static MF of 42 µT inhibits or suppresses the growth of Ehrlich ascites carcinoma (EAC) in mice. It was shown that the exposure of mice with EAC to combined MFs causes structural changes in some organs (liver, adrenal glands), which are probably due to the total degradation of the tumor tissue. In mice with transplanted EAC, the tumor tissue after exposure to weak MFs was practically absent, as distinct from control animals in which the invasion of the tumor into the adipose tissue surrounding the kidneys, mesenteric lymph nodes, and spermatic appendages was observed. In animals without tumors, no pathological deviations from the norm in the structure of organs and tissues occurred after exposure to weak MF, indicating that this factor per se is not toxic to the organism. Bioelectromagnetics 30:343–351, 2009. © 2009 Wiley‐Liss, Inc.     

Influence of a stationary magnetic field on bioelectric properties of snail neurons

Identified cells of Helix lucorum L. received 20 min exposures to 23, 120, or 200 mT stationary magnetic field (MFs). Resting potentials and input resistances were measured. Controls were instituted for temperature changes and for mechanical and other sources of artifact. Resting potentials did not change with MF exposure. Input resistances decreased significantly in normally silent cells during MF exposure, but increased significantly in spontaneously active cells. The magnitudes of changes were monotonically related to strength of the MF. Changes in excitatory postsynaptic potentials were observed during MF exposure. Elimination of perineuronal glia by proteolytic enzymes eliminated the MF effects.     

Increased vascular permeability in the circumventricular organs of adult rat brain due to stimulation by extremely low frequency magnetic fields

It has been demonstrated that the exposure of biological systems to magnetic fields (MFs) can produce several beneficial effects: tissue recovery in chronic wounds, re‐establishment of blood circulation after tissue ischemia or in necrotic tissues, improvement after epileptic episodes, angiogenesis, etc. In the current study, the effects of extremely low frequency (ELF) MF on the capillaries of some circumventricular organs (CVOs) are demonstrated; a vasodilator effect is reported as well as an increase in their permeability to non‐liposoluble substances. For this study, 96 Wistar male rats (250 g body mass) were used and divided into three groups of 32 rats each: a control group (no treatment); a sham ELF‐MF group; and an experimental group subjected to ELF‐MF (120 Hz harmonic waves and 0.66 mT, root mean square) by the use of Helmholtz coils. All animals were administered colloidal carbon (CC) intravenously to study, through optical and transmission electron microscopy, the capillary permeability in CVOs and the blood–brain barrier (BBB) in brain areas. An increase in capillary permeability to CC was detected in the ELF‐MF‐exposed group as well as a significant increase in vascular area (capillary vasodilation); none of these effects were observed in individuals of the control and sham ELF‐MF groups. It is important to investigate the mechanisms involved in the phenomena reported here in order to explain the effects of ELF‐MF on brain vasculature. Bioelectromagnetics 34:145–155, 2013. © 2012 Wiley Periodicals, Inc.