A 60 Hz magnetic field does not affect the incidence of squamous cell carcinomas in SENCAR mice

Two groups of SENCAR mice were treated with a single dose of carcinogen and then, for 23 weeks, with a chemical tumor promoter to induce skin tumors. During this period, one group was coexposed to a 2 mT power frequency (60 Hz) magnetic field, while the other was exposed to sham conditions. Application of the tumor promoter ceased after 23 weeks, but the exposure to sham conditions or magnetic fields continued for an additional 29 weeks. No difference was found between the two groups of mice in terms of the incidence of total tumors (P =.297) or squamous cell carcinomas (SSC) (P =.501). In summary, there was no evidence to support the hypotheses that 60 Hz magnetic fields (MF) can influence the development of either papillomas or SSC under our defined experimental conditions. The overall results add to previous animal studies that find no association between exposure to 60 Hz MF and the incidence of benign or malignant tumors.     

Multigeneration reproductive toxicity assessment of 60-Hz magnetic fields using a continuous breeding protocol in rats

Male and female reproductive functions have been proposed as possibly sensitive targets for the biological effects of 60-Hz (power frequency) magnetic fields (MF). However, experimental data relevant to this hypothesized association are very limited. In the present study, the "reproductive assessment by continuous breeding" design was used to identify possible effects of MF exposure on reproductive performance, fetal development, and early postnatal growth in rats. Groups of age-matched Sprague-Dawley rats (40 breeding pairs/group) were exposed continuously (18.5 hr per day) to linearly polarized, transient-free 60-Hz MF at field strengths of 0 Gauss (G; sham control), 0.02 G, 2.0 G, or 10.0 G. An additional group of 40 breeding pairs received intermittent (1 hr on/1 hr off) exposure to 10.0 G fields. F0 breeding pairs were exposed to MF or sham fields for 1 week prior to mating, during a 14-week period of cohabitation, and during a 3-week holding period after cohabitation. The duration of the cohabitation period was selected to be sufficient for the delivery of five litters in the sham control group. Pups from the final F1 litter from each breeding pair were exposed to MF or sham fields until sexual maturity, were cohabitated in MF or sham fields for 7 days with nonsiblings from the same exposure group, and were held in the MF or sham fields for 22 days to permit delivery of F2 pups for evaluation. No evidence of exposure-related toxicity was identified in any rat in the F0, F1, or F2 generations. Fetal viability and body weights in all litters of groups exposed to MF were comparable to those of sham controls. No significant differences between sham controls and MF-exposed groups were seen in any measure of reproductive performance (litters/breeding pair, percent fertile pairs, latency to parturition, litter size, or sex ratio) in either the F0 or F1 generation. Exposure of Sprague-Dawley rats to 60-Hz MF strengths of up to 10.0 G either during their peak reproductive period (F0) or during gestation and throughout their life span (F1) has no biologically significant effects on reproductive performance. These results do not support the hypothesis that exposure to pure, linearly polarized 60-Hz MF is a significant reproductive or developmental toxicant.     

Effects of low‐level 50 Hz magnetic fields on the level of host defense and on spleen colony formation

The results of 3 sets of experiments on the effects of 22 μT sinusoidal 50 Hz magnetic fields (MF), applied for 1 h on 5 successive days (1 h/5 days), on the level of host defense and on spleen colony formation are reported. The first set of experiments shows the effects on the number of colony‐forming units (CFUs) on the spleen and on the cellularity of the thymus in mice. The MF exposures resulted in an increase in CFUs which was statistically significant with respect to the controls, but not with respect to the shams. Statistically significant changes in the thymic weight and thymic index with respect to both the controls and the shams were measured 1 h after the last MF exposure. In the second set of experiments, the mice were given a sublethal dose of X‐rays (6 Gy), which was followed by exposure 2 h later to the MF. The MF exposure was repeated at the same time of day for 5 days. The number of colonies per spleen showed a consistent, statistically significant increase with MF exposure and the number of CFUs per femur was decreased. In the third set of experiments, bone marrow was taken from mice which had been exposed to 22 μT fields and injected into mice which had been exposed to a lethal dose of X‐rays (9 Gy). The number of CFUs per femur in the recipient mice was shown to be reduced by a statistically significant amount at 1 and 4 days after injection. Bioelectromagnetics 20:57–63, 1999. © 1999 Wiley‐Liss, Inc.     

Increased mouse survival, tumor growth inhibition and decreased immunoreactive p53 after exposure to magnetic fields

The possibility that magnetic fields (MF) cause antitumor activity in vivo has been investigated. Two different experiments have been carried out on nude mice bearing a subcutaneous human colon adenocarcinoma (WiDr). In the first experiment, significant increase in survival time (31%) was obtained in mice exposed daily to 70 min modulated MF (static with a superimposition of 50 Hz) having a time average total intensity of 5.5 mT. In the second independent experiment, when mice bearing tumors were exposed to the same treatment for four consecutive weeks, significant inhibition of tumor growth (40%) was reported, together with a decrement in tumor cell mitotic index and proliferative activity. A significant increase in apoptosis was found in tumors of treated animals, together with a reduction in immunoreactive p53 expression. Gross pathology at necroscopy, hematoclinical/hematological and histological examination did not show any adverse or abnormal effects. Since pharmacological rescue of mutant p53 conformation has been recently demonstrated, the authors suggest that MF exposure may obtain a similar effect by acting on redox chemistry connected to metal ions which control p53 folding and its DNA-binding activity. These findings support further investigation aimed at the potential use of magnetic fields as anti-cancer agents.     

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.     

Effect of a pulsed magnetic field on tumoral C3H/Bi female mice

Female C3H/Bi mice develop spontaneous viral mammary carcinoma which can metastasize to the lungs. Two hundred and forty tumoral mice were either exposed to a toro?dal pulsed magnetic field, 12 Hz, 100 Hz or 460 Hz in frequency or used as controls. The exposure was mainly done 10 min. a day, 3 days a week, or 30 minutes once a week from about 2 to 3 weeks after the appearance of the tumors until death. In comparison with the controls, the exposed mice showed lighter spleens and lungs; this last observation could mean fewer pulmonary metastases. The weight of the tumors has been found lighter for 460 Hz MF, not changed for 100 Hz MF, heavier for 12 Hz MF, but lifespans were not altered by the exposure.     

Extremely low frequency magnetic field effects on premorbid behaviors produced by cocaine in the mouse

We investigated the premorbid behavioral changes produced by the administration of cocaine and acute exposure to extremely low frequency (ELF) magnetic field (MF) in the mouse. ICR mice received intraperitoneal injections of cocaine at two doses (65 and 70 mg/kg) and were subsequently exposed to one of eight ELF-MF fields (2, 3, 4, 8, 10, 15, 25, or 60 Hz) of about 20 G (2 mT) intensity immediately after injection. Twelve mice were used for each of applied cocaine dose and ELF-MF level. For a given dose of cocaine, the applied MF frequencies were randomly ordered, and blind tests were carried out in which the behavior observer did not know the frequencies of MF. The premorbid behaviors were defined in the ICR mice and their changes were observed over the exposure of various ELF-MFs. Our data show that the onset times of stop rearing and tonic-clonic seizure in the 4 Hz MF exposure group are significantly different from those of the sham group.     

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.     

Carcinogenicity test in B6C3F1 mice after parental and prenatal exposure to 50 Hz magnetic fields

Some epidemiological studies suggest association of childhood cancer with occupational exposure of the parents to magnetic fields. To test this relationship, 50 each of C57BL/6J female and C3H/HeJ male mice were exposed for 2 and 9 weeks, respectively, to 50 Hz sham (group A), 0.5 (group B), and 5 mT (group C) sinusoidal alternating magnetic fields. They were mated under the exposure for up to 2 weeks, and the exposure was continued until parturition. All the B6C3F1 offspring, without adjusting numbers of animals, were clinically observed without exposure to magnetic field for a nominal 78 weeks from 6-8 weeks of age after weaning and then euthanized for pathological examination according to a routine carcinogenicity test. 540 pups entered the test, and the survival rate was 96.7%. No F1 mouse died of tumoral diseases before a male in A group died of stomach cancer at 43 weeks of age. The first animal death in the exposed groups due to tumor occurred at 71 weeks of age. Eighteen animals died before necropsy at 84-86 weeks of age. No significant difference was detected in the final number of survivors and incidence of tumors between groups A and B, or A and C. Concerning reproduction total implants in group B were less than in group A and the difference was on the borderline of significance (P=.05). This difference was not reproduced in a later duplicate experiment.     

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.     

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.     

Developmental toxicity evaluation of ELF magnetic fields in Sprague-Dawley rats

To identify possible effects of horizontally polarized magnetic field (MF) exposure on maintenance of pregnancy and embryo-fetal development, an MF exposure system was designed and constructed and 96 time-mated female Sprague-Dawley (SD) rats (24/group) received continuous exposure to 60 Hz MF at field strengths of 0 (sham control) and 5, 83.3, or 500 microT (50, 833, or 5000 mG). Dams received MF or sham exposures for 22 h/day on gestational day 6-20. MF was monitored continuously throughout the study. There were no evidences of maternal toxicity or developmental toxicity in any MF exposed groups. Mean maternal body weight, organ weights, and hematological and serum biochemical parameters in groups exposed to MF did not differ from those in sham control. No exposure related differences in fetal deaths, fetal body weight, and placental weight were observed between MF exposed groups and sham control. External, visceral, and skeletal examination of fetuses demonstrated no significant differences in the incidence of fetal malformations between MF exposed and sham control groups. In conclusion, exposure of pregnant rats to 60 Hz at MF strengths up to 500 microT during gestation day 6-20 did not produce any biologically significant effect in either dams or fetuses.     

Inhibition of pentylenetetrazole-induced seizure in mice by using a 4 Hz magnetic field: a comparative study with a 60 Hz magnetic field

We investigated the comparative effects of 4 and 60 Hz magnetic fields on pentylenetetrazole (PTZ)-induced seizure in mice. For this study, we measured the latent time to seizure, seizure duration, and lethality induced by PTZ in mice exposed to 4 and 60 Hz magnetic fields (MF) for 30 min. Compared to sham-exposed controls, the latent time to tail twitching and seizure in the 4 Hz MF group was significantly decreased while the latent time to seizure in the 60 Hz MF group was significantly increased. The seizure duration in the 4 Hz MF group was significantly decreased while that in the 60 Hz MF group was significantly increased. More importantly, while the mice exposed to a 60 Hz MF experienced significantly increased lethality after seizure convulsion, those exposed to a 4 Hz MF showed no lethality, with a shortening of the duration of seizure. This beneficial effect of a 4 Hz MF on seizure has the same implication as the anti-oxidative effects of a 4 Hz MF observed in our previous work. The results of our current and previous works indicate that a 4 Hz MF may be used as a therapeutic physical agent for the treatment of oxidative stress-induced diseases, including seizure, with or without chemical drugs.     

Effects of a 60 Hz magnetic field on photosynthetic CO2 uptake and early growth of radish seedlings

Photosynthetic CO2 uptake rate and early growth parameters of radish Raphanus sativus L. seedlings exposed to an extremely low frequency magnetic field (ELF MF) were investigated. Radish seedlings were exposed to a 60 Hz, 50 microT(rms) (root mean square) sinusoidal magnetic field (MF) and a parallel 48 microT static MF for 6 or 15 d immediately after germination. Control seedlings were exposed to the ambient MF but not the ELF MF. The CO2 uptake rate of ELF MF exposed seedlings on day 5 and later was lower than that of the control seedlings. The dry weight and the cotyledon area of ELF MF exposed seedlings on day 6 and the fresh weight, the dry weight and the leaf area of ELF MF exposed seedlings on day 15 were significantly lower than those of the control seedlings, respectively. In another experiment, radish seedlings were grown without ELF MF exposure for 14 d immediately after germination, and then exposed to the ELF MF for about 2 h, and the photosynthetic CO2 uptake rate was measured during the short-term ELF MF exposure. The CO2 uptake rate of the same seedlings was subsequently measured in the ambient MF (control) without the ELF MF. There was no difference in the CO2 uptake rate of seedlings exposed to the ELF MF or the ambient MF. These results indicate that continuous exposure to 60 Hz, 50 microT(rms) sinusoidal MF with a parallel 48 microT static MF affects the early growth of radish seedlings, but the effect is not so severe that modification of photosynthetic CO2 uptake can observed during short-term MF exposure.     

Effects of 50 Hz magnetic field exposure on tumor experimental models

The aim of this study was to investigate the interaction between a 50 Hz, 2 mT magnetic field (MF) exposure and cell growth of mammary murine adenocarcinoma, injected into experimental mice. Six different experimental protocols were performed over 2 years; several different protocols of timing of exposure were tested. X-ray radiation was adopted as the positive control. Tumor incidence and the tumor development time were calculated. No effect was observed in any experiment, and there was no statistically significant difference related to time courses among the protocols used. Neither the time of tumor cell injection nor the time of exposure produced differences between unexposed, sham, and exposed mice. When X-ray radiation was applied, the cytotoxic effect of ionizing radiation was clear, but was not increased or modified by MF exposure. Finally, the study revealed how the host-tumor system has shown a distinctive variability, unmodified by MF exposure.     

Extremely low frequency-modulated static magnetic fields to treat cancer: A pilot study on patients with advanced neoplasm to assess safety and acute toxicity

Results of a toxicity pilot human study approved by the competent ethical Committee are reported. Eleven patients with heavily pre-treated advanced cancer were enrolled in a pilot study with different schedules of time exposure to static magnetic fields (MF), amplitude modulated by ELF. An area including the neck, thoracic and abdomen was MF exposed daily, 5 days/week for 4 weeks according to two different schedules: 20 min daily (4 patients) and 70 min daily (7 patients). ECOG performance status was 1 (2 patients), 2 (8 patients), 3 (1 patient). Toxicity was assessed according to WHO criteria. ECG, Chest X-ray, physical examination, blood cell count and complete blood chemistry were performed before and at the end of the treatment. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) elevation (grade 2 toxicity) in 1 patient and microscopic urinary abnormalities in 5 patients were the only negative effects observed. We conclude that MF can be safely administrated according to the MF exposure schedules.     

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.     

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.     

DNA damage and apoptosis in the immature mouse cerebellum after acute exposure to a 1 mT, 60 Hz magnetic field.

Several recent studies have reported that whole-body exposure of rodents to power frequency magnetic fields (MFs) can result in DNA single- and double-strand breaks in the brains of these animals. The current study was undertaken to investigate whether an acute 2h exposure of a 1 mT, 60 Hz MF could elicit DNA damage, and subsequently apoptosis, in the brains of immature (10-day-old) mice. DNA damage was quantitated at 0, 2, 4, and 24h after exposure using the alkaline comet assay. Apoptosis was quantitated in the external granule cell layer (EGCL) of the immature mouse cerebellum at 0 and 24h after exposure to MF by the TdT-mediated dUTP nick-end labeling (TUNEL) assay. Four parameters (tail ratio, tail moment, comet length and tail length) were used to assess DNA damage for each comet. While increased DNA damage was detected by tail ratio at 2h after MF exposure, no supporting evidence of increased DNA damage was detected by the other parameters. In addition, no similar differences were observed using these parameters at any of the other post-exposure times. No increase in apoptosis was observed in the EGCL of MF-exposed mice, when compared to sham mice. Taken together, these results do not support the hypothesis that acute MF exposure causes DNA damage in the cerebellums of immature mice.