Chronic exposure to an extremely low‐frequency magnetic field induces depression‐like behavior and corticosterone secretion without enhancement of the hypothalamic–pituitary–adrenal axis in mice

An extremely low‐frequency magnetic field (ELF‐MF) is generated by power lines and household electrical devices. Many studies have suggested an association between chronic ELF‐MF exposure and anxiety and/or depression. The mechanism of these effects is assumed to be a stress response induced by ELF‐MF exposure. However, this mechanism remains controversial. In the present study, we investigated whether chronic ELF‐MF exposure (intensity, 3 mT; total exposure, 200 h) affected emotional behavior and corticosterone synthesis in mice. ELF‐MF‐treated mice showed a significant increase in total immobility time in a forced swim test and showed latency to enter the light box in a light–dark transition test, compared with sham‐treated (control) mice. Corticosterone secretion was significantly high in the ELF‐MF‐exposed mice; however, no changes were observed in the amount of the adrenocorticotropic hormone and the expression of genes related to stress response. Quantification of the mRNA levels of adrenal corticosteroid synthesis enzymes revealed a significant reduction in Cyp17a1 mRNA in the ELF‐MF‐exposed mice. Our findings suggest the possibility that high intensity and chronic exposure to ELF‐MF induces an increase in corticosterone secretion, along with depression‐ and/or anxiety‐like behavior, without enhancement of the hypothalamic–pituitary–adrenal axis. Bioelectromagnetics 34:43–51, 2013. © 2012 Wiley Periodicals, Inc.     

Synergic effect of retinoic acid and extremely low frequency magnetic field exposure on human neuroblastoma cell line BE(2)C

The aim of the present study was to assess whether exposure to a sinusoidal extremely low frequency magnetic field (ELF‐MF; 50 Hz, 1 mT) can affect proliferation and differentiation in the human neuroblastoma cell line BE(2)C, which is representative of high risk neuroblastomas. Cells were subjected to ELF‐MF exposure in the presence or absence of a neuronal differentiating agent (all‐trans‐retinoic acid, ATRA) for 24–72 h. In each experiment, ELF‐MF‐exposed samples were compared to sham‐exposed samples. Cells exposed to ELF‐MF combined with retinoic treatment showed a decreased cellular proliferation and an increased proportion of G₀/G₁ phase cells compared to cells exposed to either treatment alone. Moreover, ELF‐MF‐ and ATRA‐treated cells showed more differentiated morphological traits (a higher neurite number/cell, an increased neurite length), together with a significant increase of mRNA levels of p21^WAF1/CIP1 and cdk5 genes, both involved in neuronal differentiation. In addition, the expression of cyp19 gene, which is involved both in neuronal differentiation and stress response, was evaluated; cyp19 gene expression was enhanced by ATRA treatment and significantly enhanced further by ELF‐MF exposure combined with ATRA. In conclusion, our data suggest that ELF‐MF exposure can strengthen ATRA effects on neuroblastoma cells. Bioelectromagnetics 31:425–433, 2010. © 2010 Wiley‐Liss, Inc.     

Effects of exposure to a 50 Hz sinusoidal magnetic field during the early adolescent period on spatial memory in mice

Adolescence is a critical developmental stage during which substantial remodeling occurs in brain areas involved in emotional and learning processes. Although a robust literature on the biological effects of extremely low frequency magnetic fields (ELF‐MFs) has been documented, data on the effects of ELF‐MF exposure during this period on cognitive functions remain scarce. In this study, early adolescent male mice were exposed from postnatal day (P) 23–35 to a 50 Hz MF at 2 mT for 60 min/day. On P36–45, the potential effects of the MF exposure on spatial memory performance were examined using the Y‐maze and Morris water maze tasks. The results showed that the MF exposure did not affect Y‐maze performance but improved spatial learning acquisition and memory retention in the water maze task under the present experimental conditions. Bioelectromagnetics 34:275–284, 2013. © 2012 Wiley Periodicals, Inc.     

Melatonin Levels and Low‐Frequency Magnetic Fields in Humans and Rats: New Insights From a Bayesian Logistic Regression

The present analysis revisits the impact of extremely low‐frequency magnetic fields (ELF‐MF) on melatonin (MLT) levels in human and rat subjects using both a parametric and non‐parametric approach. In this analysis, we use 62 studies from review articles. The parametric approach consists of a Bayesian logistic regression (LR) analysis and the non‐parametric approach consists of a Support Vector analysis, both of which are robust against spurious/false results. Both approaches reveal a unique well‐ordered pattern, and show that human and rat studies are consistent with each other once the MF strength is restricted to cover the same range (with B ? 50 μT). In addition, the data reveal that chronic exposure (longer than ～22 days) to ELF‐MF appears to decrease MLT levels only when the MF strength is below a threshold of ~30 μT (), i.e., when the man‐made ELF‐MF intensity is below that of the static geomagnetic field. Studies reporting an association between ELF‐MF and changes to MLT levels and the opposite (no association with ELF‐MF) can be reconciled under a single framework. Bioelectromagnetics. 2019;40:539–552. © 2019 Bioelectromagnetics Society.     

Combined effects of 60 Hz electromagnetic field exposure with various stress factors on cellular transformation in NIH3T3 cells

Epidemiological studies have suggested that extremely low‐frequency magnetic fields (ELF‐MF) are associated with an increased incidence of cancer. Studies using in vitro systems have reported mixed results for the effects of ELF‐MF alone, and the World Health Organization (WHO) Research Agenda published in 2007 suggested that high priority research should include an evaluation of the co‐carcinogenic effects of ELF‐MF exposure using in vitro models. Here, the carcinogenic potential of ELF‐MF exposure alone and in combination with various stress factors was investigated in NIH3T3 mouse fibroblasts using an in vitro cellular transformation assay. NIH3T3 cells were exposed to a 60 Hz ELF‐MF (1 mT) alone or in combination with ionizing radiation (IR), hydrogen peroxide (H₂O₂), or c‐Myc overexpression, and the resulting number of anchorage‐independent colonies was counted. A 4 h exposure of NIH3T3 cells to ELF‐MF alone produced no cell transformation. Moreover, ELF exposure did not influence the transformation activity of IR, H₂O₂, or activated c‐Myc in our in vitro assay system, suggesting that 1 mT ELF‐MF did not affect any additive or synergistic transformation activities in combination with stress factors such as IR, H₂O₂, or activated c‐Myc in NIH3T3 cells. Bioelectromagnetics 33:207–214, 2012. © 2011 Wiley Periodicals, Inc.     

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.     

Effects of 50‐Hz magnetic field exposure on hormone secretion and apoptosis‐related gene expression in human first trimester villous trophoblasts in vitro

Evidence from epidemiological and animal studies showed that exposure to extremely low frequency magnetic fields (ELF‐MF) could produce deleterious effects on reproduction. In order to investigate the possible mechanism of MF exposure on reproductive effects, first trimester human chorionic villi at 8–10 weeks' gestation were obtained, and trophoblasts were isolated, cultured, and exposed to a 50‐Hz MF for different durations. The human chorionic gonadotropin (hCG) and progesterone in the culture medium was measured by electrochemiluminescence immunoassay. The mRNA levels of apoptosis‐related genes bcl‐2, bax, caspase‐3, p53, and fas in trophoblasts were analyzed using real‐time RT‐PCR. The results showed that exposure of trophoblasts to MF at 0.2 mT for 72 h did not affect secretion of hCG and progesterone from these cells. There was also no significant change in secretion of these hormones when trophoblasts were exposed to a 0.4 mT MF for 48 h. However, MF significantly inhibited hCG and progesterone secretion of trophoblasts after exposure for 72 h at 0.4 mT. Results of apoptosis‐related gene expression analysis showed that, within 72 h of exposure at 0.4 mT, there was no significant difference between MF exposure and control on the expression pattern of each gene. Based on results of the present experiment, it is suggested that exposure to MF for a longer duration (72 h) could inhibit secretion of hCG and progesterone by human first trimester villous trophoblasts, however, the effect might not be related to trophoblast apoptosis. Bioelectromagnetics 31:566–572, 2010. © 2010 Wiley‐Liss, Inc.     

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.     

Characterization of Levels of Extremely Low Frequency Magnetic Fields Emitted From Portable Hand‐Held Fans

This study aims to assess the levels of extremely low frequency magnetic fields (ELF‐MF) emitted from portable hand‐held fans (HHFs) and their principal frequency and to identify factors influencing these levels. We collected a total of eleven models of HHF and monitored the ELF‐MF as a function of fan speed and distance from the fan. EMDEX II was used to monitor the ELF‐MF. An SMP2 EMF‐meter equipped with a P400 field probe was used to determine the levels of ELF‐MF and the frequency spectrum. Ten of the fans, excluding only one bladeless‐fan model, emitted a high level of ELF‐MF near the source of the HHF direct‐current motor. The maximum measured level of ELF‐MF ranged from 14.07 to 218.7 µT. All measurements of the ELF‐MF taken within 10 cm from the HHFs showed values higher than 1.0 µT. ELF‐MF levels were found to decrease markedly with distance, regardless of the HHF product. The level of ELF‐MF rose noticeably with increased fan speed. The speed of and distance from the HHF significantly influenced the level of ELF‐MF. All principal frequencies ranged from 1 to 300 Hz, which falls in the typical range of ELF. Bioelectromagnetics. 2019;40:569–577. © 2019 Bioelectromagnetics Society.     

The effects of long-term exposure to extremely low-frequency magnetic fields on bone formation in ovariectomized rats

The effects of long‐term extremely low‐frequency magnetic field (ELF‐MF) exposure on bone formation and biochemical markers were investigated in ovariectomized rats. Sixty mature female Sprague–Dawley rats were randomly divided into four different groups (n = 15): (i) unexposed control (CTL); (ii) ovariectomized only (OVX); (iii) non‐ovariectomized, exposed (SHAM + ELF‐MF); and (iv) ovariectomized, exposed (OVX + ELF‐MF). The third and fourth groups were exposed to 1.5 mT ELF‐MF for 4 h a day for 6 months. Bone mineral density (BMD) was determined using dual energy X‐ray absorption (DEXA) measurements. The formation and resorption of bone were evaluated using bone‐specific alkaline phosphatase (BAP), osteocalcin, osteoprotogerin, and N‐telopeptide. After 6 months of ELF‐MF therapy, BMD values were significantly lower in the OVX group and higher in the OVX + ELF‐MF and SHAM + ELF‐MF groups than they were before therapy (P < 0.001). Although there was no significant difference in BMD values among the groups before therapy, the BMD values increased significantly after 6 months in the OVX + ELF‐MF and SHAM + ELF‐MF groups and were reduced in the OVX group compared to the CTL group (P < 0.001). The concentrations of BAP, osteocalcin, osteoprotogerin, and N‐telopeptide in the three experimental groups also changed in a significant way compared to the CTL group. The results of the present study suggest that osteoporosis can be inhibited by ELF‐MF stimulation treatments. It was also concluded that ELF‐MF may be useful in the prevention of osteoporosis in ovariectomized rats. Bioelectromagnetics 33:543–549, 2012. © 2012 Wiley Periodicals, Inc.     

Involvement of mitochondrial activity in mediating ELF‐EMF stimulatory effect on human sperm motility

It has recently been reported that the exposure of human spermatozoa to an extremely low frequency (ELF) electromagnetic field (EMF) with a square waveform of 5 mT amplitude and frequency of 50 Hz improves sperm motility. The functional relationship between the energy metabolism and the enhancement of human sperm motility induced by ELF‐EMF was investigated. Sperm exposure to ELF‐EMF resulted in a progressive and significant increase of mitochondrial membrane potential and levels of ATP, ADP and NAD⁺ that was associated with a progressive and significant increase in the sperm kinematic parameters. No significant effects were detected on other parameters such as ATP/ADP ratio and energy charge. When carbamoyl cyanide m‐chlorophenylhydrazone (CICCP) was applied to inhibit the oxidative phosphorylation in the mitochondria, the values of energy parameters and motility in the sperm incubated in the presence of glucose and exposed to ELF‐EMF did not change, thus indicating that the glycolysis was not involved in mediating ELF‐EMF stimulatory effect on motility. By contrast, when pyruvate and lactate were provided instead of glucose, the energy status and motility increased significantly in ELF‐EMF‐treated sperm. Under these culture conditions, the inhibition of glycolitic metabolism by 2‐deoxy‐D ‐glucose (DOG) again resulted in increased values of energy and kinematic parameters, indicating that gluconeogenesis was not involved in producing glucose for use in glycolysis. We concluded that the key role in mediating the stimulatory effects exerted by ELF‐EMF on human sperm motility is played by mitochondrial oxidative phosphorylation rather than glycolysis. Bioelectromagnetics 32:15–27, 2011. © 2010 Wiley‐Liss, Inc.     

No influence of 20 and 400 microT, 50 Hz magnetic field exposure on cognitive function in humans

The aim of the present study was to investigate cognitive effects of a continuous, vertical extremely low frequency (ELF) magnetic field (MF) of 20 and 400 microT 50 Hz in healthy young men during performance on cognitive tests. Thirty-two volunteers (20-30 years old, mean 22.6 +/- 2.2 years) participated in this double blind study. The test protocol consisted of a set of tests: divided attention, flexibility, memory updating, digit span, digit span with articulary suppression, and time perception. The total duration of the exposure was 65 min. Participants were assigned four sessions: three conditions in the helmet (sham exposure, 20 and 400 microT) and one condition out of the helmet (to control the expectancy effect). No effect of MF exposure was observed on performance.     

Sinusoidal ELF magnetic fields affect acetylcholinesterase activity in cerebellum synaptosomal membranes

The effects of extremely low frequency magnetic fields (ELF‐MF) on acetylcholinesterase (AChE) activity of synaptosomal membranes were investigated. Sinusoidal fields with 50 Hz frequency and different amplitudes caused AChE activity to decrease about 27% with a threshold of about 0.74 mT. The decrease in enzymatic activity was independent of the time of permanence in the field and was completely reversible. Identical results were obtained with exposure to static MF of the same amplitudes. Moreover, the inhibitory effects on enzymatic activity are spread over frequency windows with different maximal values at 60, 200, 350, and 475 Hz. When synaptosomal membranes were solubilized with Triton, ELF‐MF did not affect AChE activity, suggesting the crucial role of the membrane, as well as the lipid linkage of the enzyme, in determining the conditions for inactivation. The results are discussed in order to give an interpretation at molecular level of the macroscopic effects produced by ELF‐MF on biological systems, in particular the alterations of embryo development in many organisms due to acetylcholine accumulation. Bioelectromagnetics 31:270–276, 2010. © 2009 Wiley‐Liss, Inc.     

Lack of a co‐promotion effect of 60 Hz circularly polarized magnetic fields on spontaneous development of lymphoma in AKR mice

The present study was conducted to investigate the possible effect of 60 Hz circularly polarized magnetic fields (MFs) as promoters of genetically initiated lymphoma in AKR mice. One hundred sixty female animals were divided into four different groups. They were exposed to four different intensities of circularly polarized MFs. Animals received exposure to 60 Hz circularly polarized MF at field strengths (rms‐value) of 0 µT (sham control, T1, Group I), 5 µT(T2, Group II), 83.3 µT (T3, Group III), or 500 µT(T4, Group IV), for 21 h/day from the age of 4–6 weeks to the age of 44–46 weeks. There were no exposure‐related changes in mean survival time, clinical signs, body weights, hematological values, micronucleus assay, gene expression arrays, analysis of apoptosis, and necropsy findings. At histopathological examination, lymphoma was seen in all the groups. The tumor incidence was 31/40(78%), 30/40(75%), 32/40(80%), and 31/40(78%) in sham control, 5, 83.3, and 500 µT groups, respectively. However, there were no differences in the tumor incidence between the sham control (T1) and circularly polarized MF exposure groups (T2–T4). In conclusion, there was no evidence that exposure to 60 Hz circularly polarized MF strengths up to 500 µT promoted lymphoma in AKR mice. Bioelectromagnetics 31:130–139, 2010. © 2009 Wiley‐Liss, Inc.     

Novel ETV6‐RUNX1 Mouse Model to Study the Role of ELF‐MF in Childhood B‐Acute Lymphoblastic Leukemia: a Pilot Study

Exposure to extremely low‐frequency magnetic fields (ELF‐MFs) has been classified by the International Agency for Research on Cancer (IARC) as “possibly carcinogenic to humans,” based on limited scientific evidence concerning childhood leukemia. This assessment emphasized the lack of appropriate animal models recapitulating the natural history of this disease. Childhood B‐cell acute lymphoblastic leukemia (B‐ALL) is the result of complex interactions between genetic susceptibility and exposure to exogenous agents. The most common chromosomal alteration is the ETV6‐RUNX1 fusion gene, which confers a low risk of developing the malignancy by originating a preleukemic clone requiring secondary hits for full‐blown disease to appear. To develop potential prophylactic interventions, we need to identify the environmental triggers of the second hit. Recently, we generated a B‐ALL mouse model of the human ETV6‐RUNX1⁺ preleukemic state. Here, we present the results from the ARIMMORA pilot study, obtained by exposing 34 Sca1‐ETV6‐RUNX1 mice (vs. 27 unexposed) to a 50 Hz magnetic field of 1.5 mT with both fundamental and harmonic content, with an on/off cycle of 10 min/5 min, for 20 h/day, from conception until 3 months of age. Mice were monitored until 2 years of age and peripheral blood was periodically analyzed by flow cytometry. One of the exposed mice developed B‐ALL while none of the non‐exposed did. Although the results are statistically non‐significant due to the limited number of mice used in this pilot experiment, overall, the results show that the newly developed Sca1‐ETV6‐RUNX1 mouse can be successfully used for ELF‐MF exposure studies about the etiology of childhood B‐ALL. Bioelectromagnetics. 2019;40:343–353. © 2019 Bioelectromagnetics Society.     

Human electrophysiological and cognitive effects of exposure to ELF magnetic and ELF modulated RF and microwave fields: a review of recent studies

The investigation of weak (<500 microT), extremely low frequency (ELF, 0-300 Hz) magnetic field (MF) exposure upon human cognition and electrophysiology has yielded incomplete and contradictory evidence that MFs interact with human biology. This may be due to the small number of studies undertaken examining ELF MF effects upon the human electroencephalogram (EEG), and the associated analysis of evoked related potentials (ERPs). Relatively few studies have examined how MF exposure may affect cognitive and perceptual processing in human subjects. The introduction of this review considers some of the recent studies of ELF MF exposure upon the EEG, ERPs and cognitive and perceptual tasks. We also consider some of the confounding factors within current human MF studies and suggest some new strategies for further experimentation.     

Absence of daytime 50 Hz, 100 microT(rms) magnetic field or bright light exposure effect on human performance and psychophysiological parameters

The purpose of this study was to reproduce and extend two earlier studies of the effects of human exposure to 50 Hz magnetic fields (MF). In a recent paper, we described results of two double-blind investigations performed to examine effects of 100 microT(rms) 50 Hz MF exposure on psychological parameters in the same group of healthy human volunteers. In each exposure session, at 1 week intervals, with sham, continuous, and intermittent (15 s ON/OFF cycles) MF conditions, mood ratings, performance measures, and electrophysiological measures were taken. In the first study, significant amplitude changes were observed in the event-related brain potentials (ERP) recorded during a dichotic listening task. In the second study, latency and reaction time (RT) slowing were seen on a visual discrimination task (P(300) paradigm). Although these results were little related to the number of parameters analysed, they indicate that low level 50 Hz MF might have a slight influence on ERP and RT under specific circumstances of sustained attention. Before concluding that moderately strong MF exposure can influence cognitive function, previous results should be replicated, using the same paradigms with another group of healthy volunteers. In the present study, 18 healthy subjects were exposed to three experimental sessions of 30 min each, given at 1 week intervals. The sessions consisted of continuous 100 microT(rms) 50 Hz MF exposure, sham condition, and bright light (5000 lux) exposure. The study was performed double-blind, with the exposure order counter-balanced. The data on mood, ERP, RT, and other performance measures did not show any differences among the sham exposure, light exposure, and MF exposure conditions. The results of this study do not support the hypothesis that extremely low frequency (ELF) MF exposure affects the brain's electrical activity or cognitive function at field strength (100 microT(rms)) similar to that found in very close proximity of some household and industrial electrical appliances and well in excess of the average MF strength (c. 0.1 microT) found in homes. The sensitivity of the experiment was possibly not sufficient to detect an effect at this relatively low MF, and larger sample sizes would be required in further studies.     

Exposure to 50 Hz electromagnetic field raises the levels of the anti-apoptotic protein BAG3 in melanoma cells

The expression of the anti‐apoptotic protein BAG3 is induced in several cell types by exposure to high temperature, oxidants, and other stressful agents. We investigated whether exposure to 50 Hz electromagnetic fields raised BAG3 levels in the human melanoma cell line M14, in vitro and in orthotopic xenografts. Exposure of cultured cells or xenografts for 6 h or 4 weeks, respectively, produced a significant (P < 0.01) increase in BAG3 protein amounts. Interestingly, at the same times, we could not detect any significant variation in the levels of HSP70/72 protein or cell apoptosis. These results confirm the stressful effect of exposure to ELF in human cells, by identifying BAG3 protein as a marker of ELF‐induced stress. Furthermore, they suggest that BAG3 induction by ELF may contribute to melanoma cell survival and/or resistance to therapy. J. Cell. Physiol. 226: 2901–2907, 2011. © 2011 Wiley‐Liss, Inc.