Long-term exposure to extremely low-frequency magnetic fields impairs spatial recognition memory in mice

1. In the present study, we investigated the short- and long-term effects of extremely low-frequency (ELF) magnetic fields on spatial recognition memory in mice by using a two-trial recognition Y-maze that is based on the innate tendency of rodents to explore novel environments. 2. Mice were exposed to 25 or 50 Hz electromagnetic fields for either 7 (short term) or 25 days (long term) and then tested in the Y-maze. 3. The results indicated that neither short- nor long-term exposure to magnetic fields affected the locomotor activity of mice in the Y-maze. However, long-term exposure to 50 Hz fields reduced recognition of the novel arm. 4. Our findings suggest that ELF magnetic fields impair spatial recognition memory in the Y-maze depending on the field strength and/or duration of exposure.     

Genotoxic effects of extremely low frequency (ELF) magnetic fields (MF) evaluated by the Tradescantia-micronucleus assay

Extremely low frequency (ELF) electric fields (EF) and magnetic fields (MF) are generated during the production, transmission, and use of electrical energy. Although epidemiology studies suggest that there is a cancer risk associated with exposure to ELF-MF, short-term genotoxicity assays with bacteria and mammalian cells have produced inconsistent results. In the present study, we investigated the possible genotoxicity of ELF-MF by using the Tradescantia-micronucleus (Trad-MN) assay, a sensitive, reproducible, well-standardized assay for genotoxicity testing. A 50 Hz ELF-MF was generated by a laboratory exposure system consisting of a pair of parallel coils in a Helmholtz configuration. Exposure of Tradescantia (clone # 4430) inflorescences to the ELF-MF, at a flux density (B) corresponding to 1 mT, for 1, 6, and 24 h resulted in a time-dependent increase in MN frequency. The results indicate that a 50 Hz MF of 1 mT field strength is genotoxic in the Trad-MN bioassay and suggest that this assay may be suitable as a biomonitor for detecting the genotoxicity of ELF-MF in the field.     

Micronucleus induction in cells co-exposed in vitro to 50 Hz magnetic field and benzene, 1,4-benzenediol (hydroquinone) or 1,2,4-benzenetriol

The generation, transmission (e.g. power lines, transformers, service wires, and electrical panels), and use (e.g. home appliances, such as electric blankets, shavers, and televisions) of electrical energy is associated with the production of weak electric and magnetic fields (EMF) which oscillate 50 (Europe) or 60 (USA) times per second (power-line frequency), falling in the extremely-low frequency (ELF) region of the electromagnetic spectrum. Epidemiological reports suggest a possible association between exposure to ELF-EMF and an increased risk of cancer (e.g. childhood acute leukaemia). Benzene is an established human leukomogen. This xenobiotic, which is unlikely to be the ultimate carcinogen, is metabolized in the liver to its primary metabolite phenol, which is hydroxylated to hydroquinone (1,4-benzenediol) and 1,2,4-benzenetriol. In this in vitro approach, to test the genotoxic and / or co-genotoxic potency of ELF-EMF, the cytokinesis block micronucleus (MN) method with Jurkat cells has been used. A 50 Hz magnetic field (MF) of 5 mT field strength was applied for different length of time (from 1 to 24 h), either alone or with benzene, 1,4-benzenediol, or 1,2,4-benzenetriol. Our preliminary results show that, after 24 h exposure, the frequency of micronucleated cells in MF-exposed cultures is 1.9 fold higher than in sham-exposed (control) cultures. Benzene exposure does not show any cytogenetic activity, whereas 1,4-benzenediol or 1,2,4-benzenetriol alone significantly affect the number of MN in Jurkat cells, as compared to untreated cultures. Moreover, co-exposure to ELF-MF does not seem to affect the frequency of micronuclei induced by benzene, 1,4-benzenediol, or 1,2,4-benzenetriol.     

Health effects of extremely low‐frequency magnetic fields: reconsidering the melatonin hypothesis in the light of current data on magnetoreception

The so‐called ‘Melatonin Hypothesis’ proposed that decreased nocturnal production of melatonin (MLT) might explain the increased risk of breast cancer that has been formerly attributed to extremely low‐frequency (ELF) magnetic fields (MF) of weak intensity. Although the risk of ELF MF upon breast cancer was later dismissed, repeated reports were published of partial inhibition of MLT secretion in rats under long‐term (≥ 4 weeks) exposure to weak ELF MF. Since 2004, however, this topic has not been experimentally studied any more. In the present study, we propose to go back to the MLT hypothesis and apply it to childhood leukemia, for which an increased risk has been robustly associated with residential exposure to ELF MF. Contrary to the original hypothesis, however, we do not consider decreased MLT levels, but disruption of circadian rhythmicity per se as the effector mechanism. Indeed, the role of the circadian timing system in the development of childhood leukemia has been well established. Motivation for going back to the MLT hypothesis comes from recent data that suggest magnetosensory disruption by ELF MF in mammals, and magnetosensitivity in humans, together with current evidence for an influence on circadian rhythmicity from disruption of non‐photic sensory stimuli of various natures. We thus suggest further study on circadian rhythmicity in humans (children if possible) under long‐term exposure to weak ELF MF. Copyright © 2012 John Wiley & Sons, Ltd.     

The carcinogenic potential of non‐ionizing radiations: The cases of S‐50 Hz MF and 1.8 GHz GSM radiofrequency radiation

Epidemiological studies have suggested that human exposure to extremely low‐frequency electromagnetic fields from the electric power and to mobile phone radiofrequency electromagnetic fields induce an increased risk of developing malignant tumours. However, no adequate laboratory data, in particular long‐term carcinogenicity bioassays to support the epidemiological evidence, have yet been available. This motivated the Ramazzini Institute to embark on a first project of four large life‐span carcinogenic bioassays conducted on over 7000 Sprague Dawley rats exposed from prenatal life until natural death to S‐50 Hz MF alone or combined with gamma radiation or formaldehyde or aflatoxin B1. Results now available from these studies, which started concurrently, have shown that exposure to Sinusoidal‐50 Hz Magnetic Field (S‐50 Hz MF) combined with acute exposure to gamma radiation or to chronic administration of formaldehyde in drinking water induces a significantly increased incidence of malignant tumours in males and females. A second project of two large life‐span carcinogenic bioassays was conducted on over 3000 Sprague Dawley rats exposed from prenatal life until natural death to 1.8 GHz GSM of mobile phone radio base station, alone or combined with acute exposure to gamma radiation. Early results from the experiment on 1.8 GHz GSM alone show a statistically significant increase in the incidence of heart malignant schwannoma among males exposed at the highest dose.     

Haemopoietic cell proliferation in murine bone marrow cells exposed to extreme low frequency (ELF) electromagnetic fields.

As leukemia is one of the health hazards that is sometimes associated with exposure to extreme low frequency fields, we studied the in vitro effects of ELF fields on haemopoietic cell proliferation. First, the cytotoxic effect of 80 microT, 50 Hz magnetic fields on 3T3 cell proliferation was investigated using the neutral red test. Many chemicals are believed to cause damage because they interfere with basal or "housekeeping" cell functions. The basal cell functions are present in every cell. Non-specialized, actively dividing cells are suitable for measuring cytotoxic effects. Cytotoxic doses can be identified by exposing actively dividing cells in vitro and measuring growth inhibition caused by interference with these basal cell functions. 80 microT, 50 Hz magnetic fields caused no cytotoxicity: we were not able to demonstrate any interference with essential cell functions in the non-differentiated 3T3 cell line. Furthermore, the in vitro effects of ELF fields on murine haemopoietic and stromal stem cell proliferation were studied. Haemopoiesis is a continuous process, where mature blood cells are replaced by the proliferation and differentiation of more primitive progenitor and stem cells. Blood formation is tightly regulated by the stromal micro-environment. Exposure of murine bone marrow cells, from male and female mice, to 80 microT (50 Hz) magnetic fields showed a reduction in the proliferation and differentiation of the granulocyte-macrophage progenitor (CFU-GM) compared to non-exposed bone marrow cells. The results on the effect of the ELF-field on stromal stem cell proliferation (CFU-f) are somewhat equivocal at the moment. CFU-f from female mice showed a reduction while CFU-f from male mice were not decreased.     

Can cytogenetics explain the possible association between exposure to extreme low‐frequency magnetic fields and Alzheimer's disease?

Recently, a number of epidemiological studies have suggested that occupational as well as residential exposure to extreme low‐frequency electromagnetic fields (ELF‐EMFs) may be a risk factor for Alzheimer's disease. This is not proven yet and there are no known biological mechanisms to explain this alleged association. Alzheimer's disease is characterized by a number of events that have, at least partially, a genetic origin. In particular, trisomy of chromosomes 17 and 21 seems to be involved. Overall ELF‐EMFs have not been identified as genotoxic agents, but there are some papers in the scientific literature that indicate that they may enhance the effects of agents that are known to induce mutations or tumors. There are also some indications that ELF‐EMFs may induce aneuploïdy. This opens some perspectives for investigating the alleged association between ELF‐EMFs and Alzheimer's. This paper reviews the possibility of a cytogenetic association between the electromagnetic fields and Alzheimer's disease. Copyright © 2011 John Wiley & Sons, Ltd.     

Subchronic effects on leukocyte-endothelial interactions in mice by whole body exposure to extremely low frequency electromagnetic fields

Abstract. In the present study, we measured and quantified changes in leukocyte behavior in the subcutaneous microcirculation in vivo and examined serum cytokine levels in vitro while mice were exposed to continuous 50 Hz electromagnetic fields for 17 days. Mice were exposed to 50 Hz sinusoidal electromagnetic fields at magnetic densities of 0.3, 1.0 and 3.0 mT. The intramicrovascular behavior of leukocytes was evaluated by fluorescence microscopy using a dorsal skinfold chamber technique. Significantly increased endothelial-adhering leukocytes were observed only in the 3.0 mT exposure group, but no changes were detected in serum TNF-alpha and IL-1beta levels. Subsequently, long-term continuous whole body exposure to 50 Hz electromagnetic fields elicited leukocyte-endothelium interactions, however, this effect does not appear to be controlled by cytokine levels.     

In vitro assessment of clastogenicity of mobile-phone radiation (835 MHz) using the alkaline comet assay and chromosomal aberration test

Recently we demonstrated that 835-MHz radiofrequency radiation electromagnetic fields (RF-EMF) neither affected the reverse mutation frequency nor accelerated DNA degradation in vitro. Here, two kinds of cytogenetic endpoints were further investigated on mammalian cells exposed to 835-MHz RF-EMF (the most widely used communication frequency band in Korean CDMA mobile phone networks) alone and in combination with model clastogens: in vitro alkaline comet assay and in vitro chromosome aberration (CA) test. No direct cytogenetic effect of 835-MHz RF-EMF was found in the in vitro CA test. The combined exposure of the cells to RF-EMF in the presence of ethylmethanesulfonate (EMS) revealed a weak and insignificant cytogenetic effect when compared to cells exposed to EMS alone in CA test. Also, the comet assay results to evaluate the ability of RF-EMF alone to damage DNA were nearly negative, although showing a small increase in tail moment. However, the applied RF-EMF had potentiation effect in comet assay when administered in combination with model clastogens (cyclophosphamide or 4-nitroquinoline 1-oxide). Thus, our results imply that we cannot confidently exclude any possibility of an increased risk of genetic damage, with important implications for the possible health effects of exposure to 835-MHz electromagnetic fields.     

Evaluation of testicular degeneration induced by low-frequency electromagnetic fields

The population exposure to electromagnetic fields (EMF) has been growing in recent decades. The generation, distribution and use of electric energy can generate low-frequency electromagnetic fields. The present study investigates the effects of EMF (60 Hz and 1 mT) on spermatogenesis of rats during different periods of maturation. Wistar rats were exposed to EMF from day 13 of gestation to postnatal day 21 or 90 in three daily applications of 30 min. Plasma testosterone concentration was not changed by EMF exposure; however, histopathological and histomorphometrical analyses of the testes showed testicular degeneration in a subset of animals exposed to EMF. The magnitude of the degenerative process varied between those individuals affected, indicating different individual sensitivity to EMF. The main alterations observed through transmission electron microscopy were highly electron-dense mitochondria with loss of their organization and cristae. Exposure to 60 Hz and 1 mT EMF can disturb spermatogenesis and may produce subfertility or infertility.     

Effect of an acute 900MHz GSM exposure on glia in the rat brain: a time-dependent study

Because of the increasing use of mobile phones, the possible risks of radio frequency electromagnetic fields adverse effects on the human brain has to be evaluated. In this work we measured GFAP expression, to evaluate glial evolution 2, 3, 6 and 10 days after a single GSM exposure (15min, brain averaged SAR=6W/kg, 900MHz signal) in the rat brain. A statistically significant increase of GFAP stained surface area was observed 2 days after exposure in the frontal cortex and the caudate putamen. A smaller statistically significant increase was noted 3 days after exposure in the same areas and in the cerebellum cortex. Our results confirm the Mausset-Bonnefont et al. study [Mausset-Bonnefont, A.L., Hirbec, H., Bonnefont, X., Privat, A., Vignon, J., de Seze, R., 2004. Acute exposure to GSM 900MHz electromagnetic fields induces glial reactivity and biochemical modifications in the rat brain. Neurobiol. Dis. 17, 445-454], showing the existence of glial reactivity after a 15min GSM acute exposure at a brain averaged SAR of 6W/kg. We conclude to a temporary effect, probably due to a hypertrophy of glial cells, with a temporal and a spatial modulation of the effect. Whether this effect could be harmful remains to be studied.     

Mobile telephones and cancer--a review of epidemiological evidence

There is considerable public concern about possible long-term adverse health effects of mobile phones. While there is scientific controversy about long-term health effects of high-frequency electromagnetic fields lasting for at least 50 yr, the rise and success of mobile telecommunication made it necessary to investigate the problem more comprehensively and assess the possible risk cautiously because never before in history has a substantial proportion of the population been exposed to microwaves in the near field and at comparably high levels. Because the mostly localized exposure target region is the head, most epidemiological studies focus on brain tumors. Overall nine epidemiological studies have been published, four from the United States, two from Sweden, and one each from Denmark, Finland, and Germany. Seven studies were mainly on brain tumors, with one investigating in addition to brain tumors salivary gland cancer and another cancer of the hematopoietic and lymphatic tissues, and one examining intraocular melanoma. All studies have some methodological deficiencies: (1) too short duration of mobile phone use to be helpful in risk assessment, (2) exposure was not rigorously determined, and (3) there is a possibility of recall and response error in some studies. Nevertheless, all studies approaching reasonable latencies found an increased cancer risk associated with mobile phone use. Estimates of relative risk in these studies vary between 1.3 and 4.6 with highest overall risk for acoustic neuroma (3.5) and uveal melanoma (4.2), and there is evidence for enhanced cancer risk with increasing latency and duration of mobile phone use.     

Recent advances in research on radiofrequency fields and health: 2001-2003

The widespread use of wireless telecommunications devices, particularly mobile phones, has resulted in increased human exposure to radiofrequency (RF) fields. Although national and international agencies have established safety guidelines for exposure to RF fields, concerns remain about the potential for adverse health outcomes to occur in relation to RF field exposure. The extensive literature on RF fields and health has been reviewed by a number of authorities, including the Royal Society of Canada (1999), the European Commission's Scientific Committee on Toxicity, Ecotoxicity, and the Environment (CSTEE, 2001), the British Medical Association (2001), the Swedish Radiation Protection Authority (Boice & McLaughlin, 2002), and the Health Council of The Netherlands (2002). This report provides an update on recent research results on the potential health risks of RF fields since the publication of the Royal Society of Canada report in 1999 (See Krewski et al., 2001a) and our previous 2001 update (Krewski et al., 2001b), covering the period 2001-2003. The present report examines new data on dosimetry and exposure assessment, biological effects such as enzyme induction, and toxicological effects, including genotoxicity, carcinogenicity, and testicular and reproductive outcomes. Epidemiological studies of mobile phone users and occupationally exposed populations are examined, along with human and animal studies of neurological and behavioral effects. All of the authoritative reviews completed within the last 2 yr have concluded that there is no clear evidence of adverse health effects associated with RF fields. However, following a recent review of nine epidemiological studies of mobile phones and cancer, Kundi et al. (2004) concluded that the possibility of an enhanced cancer risk cannot be excluded. These same reviews support the need for further research to clarify the possible associations between RF fields and adverse health outcomes that have appeared in some reports. The results of the ongoing World Health Organization (WHO) study of mobile phones will provide important new information in this regard.     

MOBILE TELEPHONES AND CANCER—A REVIEW OF EPIDEMIOLOGICAL EVIDENCE

There is considerable public concern about possible long-term adverse health effects of mobile phones. While there is scientific controversy about long-term health effects of high-frequency electromagnetic fields lasting for at least 50yr, the rise and success of mobile telecommunication made it necessary to investigate the problem more comprehensively and assess the possible risk cautiously because never before in history has a substantial proportion of the population been exposed to microwaves in the near field and at comparably high levels. Because the mostly localized exposure target region is the head, most epidemiological studies focus on brain tumors. Overall nine epidemiological studies have been published, four from the United States, two from Sweden, and one each from Denmark, Finland, and Germany. Seven studies were mainly on brain tumors, with one investigating in addition to brain tumors salivary gland cancer and another cancer of the hematopoietic and lymphatic tissues, and one examining intraocular melanoma. All studies have some methodological deficiencies: (1) too short duration of mobile phone use to be helpful in risk assessment, (2) exposure was not rigorously determined, and (3) there is a possibility of recall and response error in some studies. Nevertheless, all studies approaching reasonable latencies found an increased cancer risk associated with mobile phone use. Estimates of relative risk in these studies vary between 1.3 and 4.6 with highest overall risk for acoustic neuroma (3.5) and uveal melanoma (4.2), and there is evidence for enhanced cancer risk with increasing latency and duration of mobile phone use.     

极低频电磁场对不同性别断乳小鼠学习记忆能力的影响

目的：探讨极低频电磁场对不同性别断乳小鼠学习记忆能力的影响。方法采用50 Hz,2.0 mT电磁场对断乳后的雌性、雄性小鼠进行长期磁场照射（1h/d,连续2周）,对照组进行假照射,应用Y-迷宫实验观察各组小鼠的学习记忆能力。结果经电磁场照射后,雌性和雄性磁场组小鼠进入各个臂的时间、次数以及时间、次数百分比与各自对照组比较,差异无统计学意义（P〉0.05）,雌性对照组与雄性对照组进入各个臂的时间、次数比较,差异无统计学意义（P〉0.05）。结论50 Hz,2.0 mT极低频电磁场对不同性别小鼠在Y-迷宫中的学习记忆无影响,并且在学习记忆能力上雌雄性别无差异。     

Mobile Phones,Non-Ionizing Radiofrequency Fields and Brain Cancer: Is There an Adaptive Response?

There is widespread concern among the general public regarding the ever increasing use of mobile phones. The concern is mainly because the antenna which transmits nonionizing radiofrequency fields is held close to the head during use and thus might cause brain cancer. By far, the largest epidemiological study was conducted by the INTER-PHONE study group and the results were published in 2011. The author’s conclusions were (i) no increased risk of meningioma and glioma in mobile phone users and (ii) there were suggestions of an increased risk for glioma at the highest exposure levels but, bias and error prevented a causal interpretation. We have carefully examined all of the odd ratios presented in the INTERPHONE study publication: our results showed 24.3% decreased and 0.7% increased risk for meningioma and 22.1% decreased and 6.6% increased risk for glioma. Hence, we hypothesize that the overwhelming evidence for the decreased risk for both diseases may be due to the induction of ‘adaptive response’ which is well-documented in scientific literature     

Short‐ and long‐term exposure to alternating magnetic field (50 Hz, 0.5 mT) affects rat pituitary ACTH cells: Stereological study

The aim of the present study was to determine does extremely low frequency magnetic field (ELF‐MF, 50 Hz, 0.5 mT) affect pituitary adrenocorticotroph (ACTH) cells in adult animals. We performed two series of experiments: (1) short‐term exposure of 3‐month‐old rats to ELF‐MF for 1 and 7 days, and (2) long‐term exposure of rats to ELF‐MF from their conception to 3 months of age. Stereological study was performed on immunolabeled pituitary ACTH cells. The total number and volume of ACTH cells, the volume of their nuclei and pituitary volume were measured. ELF‐MF exposure for 1 day significantly decreased total number and volume of ACTH cells, the volume of their nuclei, as well as pituitary volume. ELF‐MF exposure for 7 days significantly reduced only the volume of ACTH cells. Life‐long exposure to ELF‐MF induced decrease in the volume of ACTH cells and pituitary volume. We can conclude that the applied ELF‐MF has a strong influence on morphometrical parameters of the pituitary ACTH cells and could be considered as a stressogenic factor. © 2014 Wiley Periodicals, Inc. Environ Toxicol 31: 461–468, 2016.     

Exposure to ELF magnetic fields modulate redox related protein expression in mouse macrophages

The interaction of extremely low frequency (ELF) magnetic fields (MF) with cells can induce alterations in various cell physiological processes. Here, we present evidence that exposure of mouse macrophages to 50 Hz, 1.0 mT MF lead to immune cell activation seen as increased production of reactive oxygen species (ROS), and also to modulation on the expression level of important proteins acting in redox regulatory processes and thus explaining the noted changes in ROS levels seen after exposure. The MF exposure caused slight and transient decreases after short term exposures (2 h or less) of clathrin, adaptin, PI3-kinase, protein kinase B (PKB) and PP2A, whereas longer exposures had no effect. The levels of the NAD(P)H oxidase subunit gp91phox oscillated between increased and normal levels compared to controls. The stress proteins Hsp70 and Hsp110 exhibited increased levels at certain time points, but not generally. The effects of MF on protein levels are different from the effects exerted by 12-O-tetradecanolyphobol-13-acetate (TPA) or LPS, although all three factors cause increases in ROS release. This suggests that ELF MF interacts with other cellular constituents than these chemicals, although induced pathways at least partially converge.     

Extremely low-frequency electromagnetic field (ELF-EMF) does not affect the expression of alpha3, alpha5 and alpha7 nicotinic receptor subunit genes in SH-SY5Y neuroblastoma cell line

Neuronal nicotinic acetylcholine receptors (nAChRs) are involved in a number of functional processes, including cognition, learning and memory, and alterations in their expression and/or activity have been implicated in various neurological disorders such as Alzheimer's disease (AD), Parkinson's disease and schizophrenia. Epidemiological studies have shown that exposure to electromagnetic fields (EMF) may contribute to the pathogenesis of neurodegenerative diseases such as Alzheimer's disease. Given the role of nAChRs in physiological and pathological conditions, we wondered whether an extremely low-frequency electromagnetic field (ELF-EMF) may affect the expression of the molecules involved in neurodegenerative processes. In order to investigate this possibility, we studied the expression of alpha3, alpha5 and alpha7 nicotinic subunits upon exposure of the SH-SY5Y human neuroblastoma cell line to a 50 Hz power-line magnetic field in a "blind trial" system; various magnetic flux densities and exposure times were applied. Our studies show that the expression of some relevant components of the cholinergic nicotinic system, which is one of the most affected neurotransmission systems in AD, did not undergo any change at molecular level by environmental exposure to ELF-EMF.     

Extremely Low Frequency Magnetic Fields Modulate Bicuculline-lnduced-Convulsion in Rats

The effect of extremely low frequency (ELF, 60 Hz) magnetic fields (MFs) on convulsions was investigated in rats. We determined the onset and duration of convulsions induced by bicuculline alone or by co-exposure to MFs and bicuculline. In addition, we measured the GABA concentrations in the rat brains using HPLC-ECD. MFs strengthened the convulsion induced by bicuculline (0.3, 1, and 3 microg, i.c.v.), with a shortening of the onset time, but lengthening of the duration time. Co-exposure to MFs and bicuculline decreased the GABA levels in the cortex, hippocampus and hypothalamus, whereas MFs alone reduced the level of GABA only in the hippocampus. These results suggest that the exposure to MFs may modulate bicuculline-induced convulsions due to GABA neurotransmissions in rat brains.