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Developmental effects of physiologically weak electric fields and heat: an overview.

This study summarizes the possible effects on prenatal development of physiologically weak electric fields induced in the body by exposure to extremely low frequency (ELF) electromagnetic fields and of elevated temperature levels that might result from exposure to radiofrequency (RF) radiation. Both topics have been discussed at recent international workshops organized by WHO in collaboration with other bodies. Mammalian development is characterized by a highly ordered sequence of cell proliferation and differentiation, migration, and programmed cell death. These processes, particularly proliferation and migration, are susceptible to a variety of environmental agents including raised maternal temperature. In addition, there is growing evidence that physiologically weak endogenous DC electric fields and ionic currents have a role in guiding developmental processes, including cell orientation and migration, by establishing electrical potential gradients. Disruption of these fields can adversely affect development in amphibian and bird embryos, which are experimentally accessible, and may well do so in mammalian embryos. The extent to which induced ELF electric fields might influence these and other processes that take place during prenatal development, childhood, and adolescence is less clear. Organogenesis, which takes place primarily during the embryonic period, is susceptible to raised maternal temperatures; a large number of studies have shown that RF exposure produces developmental effects that can be attributed to heat. The development of the central nervous system is particularly susceptible to raised temperatures; a reduction in brain size, which results in a smaller head, is one of the most sensitive markers of heat-induced developmental abnormalities and can be correlated with heat-induced behavioral deficits. However, some aspects of CNS development have been less well explored, particularly effects on corticogenesis. In addition, the persistence of CNS developmental sensitivity through to childhood and adolescence is not clear.

Aging↗

Effects of a 50 Hz electric field on plasma lipid peroxide level and antioxidant activity in rats.

The effects of exposure to extremely low frequency electric fields (ELF EFs) on plasma lipid peroxide levels and antioxidant activity (AOA) in Sprague-Dawley rats were studied. The test was based on comparisons among rats treated with a combination of the oxidizing agent, 2,2'-azobis(2-aminopropane) dihydrochloride (AAPH) and 50 Hz EF of 17.5 kV/m intensity for 15 min per day for 7 days, AAPH alone, EF alone or no treatment. EF significantly decreased the plasma peroxide level in rats treated with AAPH, similar to treatment by ascorbic acid or the superoxide dismutase. Ascorbic acid increased AOA; however, EF and superoxide dismutase did not change AOA compared with sham exposure in stressed rats. No influence on the lipid peroxide level and AOA in unstressed rats was observed with EF exposure alone. Although the administration of AAPH decreased AOA, this decrease did not change when EF was added. These data indicate that the ELF EF used in this study influenced the lipid peroxide level in an oxidatively stressed rat.

Amidines↗

Influence of 50 Hz magnetic field on sex hormones and other fertility parameters of adult male rats.

The effects of an extremely low frequency (ELF) magnetic field on the sex hormones and other fertility parameters of adult male Sprague-Dawley rats were investigated. Adult male rats were exposed to a 50 Hz sinusoidal magnetic field at approximately 25 microT (rms) for 18 consecutive weeks. There were no significant effects on the absolute body weight and the weight of the testes of the exposed rats. However, the weights of seminal vesicles and preputial glands were significantly reduced in the exposed male rats. Similarly, a significant reduction in sperm count was observed in the exposed group. Furthermore, there were no significant effects on the serum levels of male follicle stimulating hormone (FSH) during the 18 weeks of exposure period. On the other hand, there was a significant increase in the serum levels of male luteinizing hormone (LH) after 18 weeks of exposure (P < .005), while testosterone levels were significantly decreased only after 6 and 12 weeks of the exposure period. These results suggest that long term exposure to ELF could have adverse effects on mammalian fertility and reproduction.

Animals↗

A possible involvement of beta-endorphin, substance P, and serotonin in rat analgesia induced by extremely low frequency magnetic field.

Most of the research concerning magnetic antinociception was focused on brief exposure less than 1 h. The main purpose of the present study was to determine the effect of extremely low frequency (ELF) magnetic field (MF) repeated exposures on rats in inducing antinociception and to find the effective analgesic "time window." Meanwhile this investigation was to examine the role of central beta-endorphin, substance P, and 5-HT in magnetic analgesia. We found tail flick latencies (TFLs) increased significantly after the rats were exposed to 55.6 Hz, 8.1 mT magnetic field for 4 days, 6 h each day. The analgesic effects seemed to decrease gradually when the rats were exposed daily for another 10 days. Their levels of TFLs decreased within 1 day when the rats were removed after a 4-day exposure. The concentrations of hypothalamus beta-endorphin, substance P, and brainstem serotonin (5-HT) were increased significantly on Day 4. However, no differences were found when rats were exposed for another 10 days, and there were no significant increases when rats were removed after the fourth day of exposure and tested for nociception on Days 5 and 7 with no changes in the biochemical markers at 7 days. These results suggest that the ELF magnetic field has analgesic effect, but only on Days 3 and 4. The effect may be associated with increases in endogenous beta-endorphin, substance P, and 5-HT stimulated by the 55.6 Hz, 8.1 mT magnetic field.

Analgesia↗

Effects of a 50 Hz magnetic field on Dictyostelium discoideum (Protista).

Some studies have demonstrated that a few biological systems are affected by weak, extremely low frequency (ELF) electromagnetic fields (EMFs), lower than 10 mT. However, to date there is scanty evidence of this effect on Protists in the literature. Due to their peculiarity as single-cell eukaryotic organisms, Protists respond directly to environmental stimuli, thus appearing as very suitable experimental systems. Recently, we showed the presence of propionylcholinesterase (PrChE) activity in single-cell amoebae of Dictyostelium discoideum. This enzyme activity was assumed to be involved in cell-cell and cell-environment interactions, as its inhibition affects cell aggregation and differentiation. In this work, we have exposed single-cell amoebae of D. discoideum to an ELF-EMF of about 200 microT, 50 Hz, for 3 h or 24 h at 21 degrees C. A delay in the early phase of the differentiation was observed in 3 h exposed cells, and a significant decrease in the fission rate appeared in 24 h exposed cells. The PrChE activity was significantly lower in 3 h exposed cells than in the controls, whereas 24 h exposed cells exhibited an increase in this enzyme activity. However, such effects appeared to be transient, as the fission rate and PrChE activity values returned to the respective control values after a 24 h stay under standard conditions.

Animals↗

Extremely low frequency electromagnetic field exposure promotes differentiation of pituitary corticotrope-derived AtT20 D16V cells.

The pituitary corticotrope-derived AtT20 D16V cell line responds to nerve growth factor (NGF) by extending neurite-like processes and differentiating into neurosecretory-like cells. The aim of this work is the study of the effect of extremely low frequency electromagnetic fields (ELF-EMF) at a frequency of 50 Hz on these differentiation activities. To establish whether exposure to the field could influence the molecular biology of the cells, they were exposed to a magnetic flux density of 2 milli-Tesla (mT). Intracellular calcium ([Ca2+]i) and intracellular pH (pHi) were monitored in single exposed AtT20 D16V cells using fluorophores Indo-1 and SNARF for [Ca2+]i and pHi, respectively. Single-cell fluorescence microscopy showed a statistically significant increase in [Ca2+]i followed by a drop in pHi in exposed cells. Both scanning electron microscopy (SEM) and transmission microscopy of exposed AtT20 D16V cells show morphological changes in plasma membrane compared to non-exposed cells; this modification was accompanied by a rearrangement in actin filament distribution and the emergence of properties typical of peptidergic neuronal cells-the appearance of secretory-like granules in the cytosol and the increase of synaptophysin in synaptic vesicles, changes typical of neurosecretory-like cells. Using a monoclonal antibody toward the neurofilament protein NF-200 gave additional evidence that exposed cells were in an early stage of differentiation compared to control. Pre-treatment with 0.3 microM nifedipine, which specifically blocks L-type Ca2+ channels, prevented NF-200 expression in AtT20 D16V exposed cells. The above findings demonstrate that exposure to 50 Hz ELF-EMF is responsible for the premature differentiation in AtT20 D 16 V cells.

Actin Cytoskeleton↗

Elevated sister chromatid exchange frequencies in dividing human peripheral blood lymphocytes exposed to 50 Hz magnetic fields.

The in vitro cytomolecular technique, sister chromatid exchange (SCE), was applied to test the clastogenic potentiality of extremely low frequency (ELF) electromagnetic fields (EMFs) on human peripheral blood lymphocytes (HPBLs). SCE frequencies were scored in dividing peripheral blood lymphocytes (PBLs) from six healthy male blood donors in two rounds of experiments, R1 and R2, to determine reproducibility. Lymphocyte cultures in the eight experiments conducted in each round were exposed to 50 Hz sinusoidal (continuous or pulsed) or square (continuous or pulsed) MFs at field strengths of 1 microT or 1 mT for 72 h. A significant increase in the number of SCEs/cell in the grouped experimental conditions compared to the controls was observed in both rounds. The highest SCE frequency in R1 was 10.03 for a square continuous field, and 10.39 for a square continuous field was the second highest frequency in R2. DNA crosslinking at the replication fork is proposed as a model which could explain the mechanistic link between ELF EMF exposure and increased SCE frequency.

Bromodeoxyuridine↗

Modulation of tendon fibroplasia by exogenous electric currents.

A chicken tendon explant model system has been developed to investigate the effects of extremely-low-frequency (ELF), low-amplitude, unipolar, square wave pulsed electric fields on fibroplasia in vitro. An electric field parameter set consisting of 1-Hz, 1-ms duration pulses, with a time-averaged current density of 7 mA/m2 (peak current density 7 A/m2) induced maximal (32%) increase in fibroblast proliferation in tendon explants exposed for 4 days. Exposure to the same field at an average current density of 1.8 mA/m2 had no effect on fibroblast proliferation, whereas exposure to current densities on greater than 10 mA/m2 inhibited proliferation and relative collagen synthesis, without affecting noncollagen protein synthesis. Fibroplasia was significantly increased in explants oriented parallel to applied electric fields having current densities of 3.5 or 7 mA/m2, but there was no detectable effect on explants oriented perpendicular to the same electric field. Fibroblast proliferation and relative collagen synthesis were inversely proportional to donor age for chickens in the 3- to 16-week age group used in this study. For these dependent variables (proliferation and relative collagen synthesis), there was no interaction between donor age and ELF electric field exposure.

Animals↗

Lithium as a normal metabolite: some implications for cyclotron resonance of ions in magnetic fields.

Cyclotron resonance of ions has been proposed as a mechanism by which weak, extremely-low-frequency (ELF) electromagnetic fields can act on biological systems. Critics of a mechanism predicated on resonance of lithium have argued that this element is virtually absent from the internal milieu of mammals and otherwise plays no role in the normal physiological functioning of the organism. Sophisticated techniques of trace-element analysis have recently revealed that lithium is a normal constituent of tissues of assayed mammals, including those of rats and human beings. There is evidence, too, that lithium is an important, biologically-active element. Cyclotron resonance may or may not be a mechanism by which ELF- and static-magnetic fields at low strengths combine to affect the organism, but rejection of this mechanism on the grounds that lithium is absent or is physiologically inadequate is unwarranted. Lithium is normally present and is metabolically active in many tissues, especially those of the neuroendocrine system.

Animals↗

Statistical approach to combining the results of similar experiments, with application to the hematologic effects of extremely-low-frequency electric field exposures.

A large proportion of scientific effort in investigating the possible biological effects of exposure to extremely-low-frequency (ELF) fields consists of laboratory studies on experimental animals. Most experiments in which hematologic properties are measured show no statistically significant effect due to exposure. However, some studies show significant effects which, in general, are not clearly reproducible. A difficult question must then be addressed: Are these relatively few indications of ELF effects statistical artifacts due to the increased risk of a type I error in multiple studies, or is there a real biological effect that is undetected in most studies due to the relatively small sample sizes commonly used? A statistical approach for examining the accumulated results of multiple experiments which results in a single test for treatment effect is presented. The technique requires very mild assumptions, and is valid for experiments that vary widely in specific characteristics such as exposure level, duration, and laboratory. The method is applied to the results of a collection of hematologic and serum chemistry experiments, and the combined results indicate the existence of experimental effects on some end points.

Animals↗

Extremely-low-frequency and very-low-frequency magnetic fields emitted by video display units.

Extremely-low-frequency (ELF) and very-low-frequency (VLF) magnetic fields as emitted by monochrome and multichrome video display units (VDUs) were measured for their frequency domains. The rms magnetic-flux densities (MFDs) were measured as a function of distance from all six sides of VDUs of four types. The MFDs at a distance of 30 cm from the screen (defined as the operator's position) were between 0.06 and 0.6 microT in the ELF range and between 0.02 and 0.06 microT in the VLF range. The contribution of harmonics to the total MFD was the same for both frequency ranges, less than 6%. For the first three harmonics, the MFD of each higher harmonic was one-half that of the immediately lower harmonic.

Computer Terminals↗

The influence of temperature during electric- and magnetic-field-induced alteration of calcium-ion release from in vitro brain tissue.

A technique based on release of calcium ions from in vitro preparations of avian brain tissues has been used by several investigators to demonstrate a biological effect of weak electric and magnetic fields. When the tissues have been exposed to ELF-modulated, VHF or UHF fields, enhanced release of calcium ions has resulted. In contrast, when the tissues have been exposed directly to an ELF field, outcomes have differed. Both inhibition and enhancement in release of calcium ions have been reported. We now find that either outcome--or a null result--is possible, depending on the temperature of tissue samples before and during exposure. Avian-brain tissues were exposed to 16-Hz sinusoidal electromagnetic fields at 14.1 Vrms/m (in air) and 64 nTrms. During 20-min exposures, as tissue-sample temperature rose by 0.7 to 2.5 degrees C to a final temperature of 35, 36, or 37, but not of 38 or 39 degrees C, an enhanced release of ions was observed. When the temperature was stable during exposure (i.e., constant within +/- 0.3 degrees C) at a final value of 36 or 37, but not of 35 or 38 degrees C, the quantity of ions released was reduced. And when descending by 0.7 to 1.5 degrees C to any final temperature from 35 to 38 degrees C, a null result occurred. These findings may reconcile the apparent disagreement in the direction of a field-induced response, and they may explain why experimental outcomes have been difficult to confirm in some laboratories. Of greater importance, the findings may also provide insight into the mechanism of the field-induced phenomenon.

Animals↗

Transcription in Drosophila melanogaster salivary gland cells is altered following exposure to low-frequency electromagnetic fields: analysis of chromosome 3R.

The use of the transcription autoradiographic method permits identification of nascent RNA chains directly on identifiable regions of Drosophila salivary gland chromosomes. Changes in transcriptional activity at 13 defined regions of the right arm of chromosome 3 (3R) were observed following 20-min exposures of salivary glands to five different extremely low frequency (ELF) electromagnetic (EM) fields. Changes in translational patterns were also induced by the ELF EM fields in exposed cells. Differences included an increase in over-all polypeptide synthesis as well as in the number of polypeptides resolved in cells exposed to EM fields.

Animals↗

The role of coherence time in the effect of microwaves on ornithine decarboxylase activity.

Previously, we demonstrated the requirements for a minimum coherence time of an applied, small amplitude (10 microT) ELF magnetic field if the field were to produce an enhancement of ornithine decarboxylase activity in L929 fibroblasts. Further investigation has revealed a remarkably similar coherence time phenomenon for enhancement of ornithine decarboxylase activity by amplitude-modulated 915 MHz microwaves of large amplitude (SAR 2.5 W/kg). Microwave fields modulated at 55, 60, or 65 Hz approximately doubled ornithine decarboxylase activity after 8 h. Switching modulation frequencies from 55 to 65 Hz at coherence times of 1.0 s or less abolished enhancement, while times of 10 s or longer provided full enhancement. Our results show that the microwave coherence effects are remarkably similar to those observed with ELF fields.

Animals↗

Chick embryo development can be irreversibly altered by early exposure to weak extremely-low-frequency magnetic fields.

Several reports have shown that weak, extremely-low-frequency (ELF), pulsed magnetic fields (PMFs) can adversely affect the early embryonic development of the chick. In this study, freshly fertilized chicken eggs were exposed during the first 48 h of postlaying incubation to PMFs with 100 Hz repetition rate, 1.0 microT peak-to-peak amplitude, and 500 microseconds pulse duration. Two different pulse waveforms were used, having rise and fall times of 85 microseconds (PMF-A) or 2.1 microseconds (PMF-B). It has been reported that, with 2 day exposure, these fields significantly increase the proportion of developmental abnormalities. In the present study, following exposure, the eggs were allowed to incubate for an additional 9 days in the absence of the PMFs. The embryos were taken out of the eggs and studied blind. Each of the two PMF-exposed groups showed an excess in the percentage of developmental anomalies compared with the respective sham-exposed samples. This excess of anomalies was not significant for the PMF-A-treated embryos (P = 0.173), whereas it was significant for the PMF-B-exposed group (P = 0.007), which showed a particularly high rate of early embryonic death. These results reveal that PMFs can induce irreversible developmental alterations and confirm that the pulse waveform can be a determinant factor in the embryonic response to ELF magnetic fields. The data also validate previous work based on the study of PMFs' effects at day 2 of embryonic development under field exposure.

Abnormalities, Radiation-Induced↗

Behavioral sensitivity of rats to extremely-low-frequency magnetic fields.

Work in our laboratory has revealed autonomic and/or behavioral sensitivity of mice, rats, and a domestic fowl to extremely-low-frequency (ELF) or nominally static magnetic (B) fields at flux densities between 250 and 1700 microT (rms). To extend our work, an automated exposure and data-acquisition system was used with the technique of conditional suppression to assess behavioral sensitivity to time-varying B fields. Each of five rats was exposed aperiodically to a B field during 3 min warning periods that terminated in a brief electric shock. The difference between rates of lever pressing during B-field warning periods and rates during immediately antecedent, 3 min control periods was analyzed at frequencies of 7, 16, 30, 60, and 65.1 Hz. To produce equivalent induced voltages in the rat at each frequency, graded flux densities were established that ranged from 1900 microT at 7 Hz to 200 microT at 65.1 Hz. Analysis of differences in lever-pressing rates revealed that in a given session of testing the rats would increasingly suppress responding when exposed to a B field, but this trend was independent of frequency. This experiment provides evidence of behavioral sensitivity by a mammal to an ELF magnetic field.

Analysis of Variance↗

Weak extremely-low-frequency magnetic fields and regeneration in the planarian Dugesia tigrina.

Extremely-low-frequency (ELF), low-intensity magnetic fields have been shown to influence cell signaling processes in a variety of systems, both in vivo and in vitro. Similar effects have been demonstrated for nervous system development and neurite outgrowth. We report that regeneration in planaria, which incorporates many of these processes, is also affected by ELF magnetic fields. The rate of cephalic regeneration, reflected by the mean regeneration time (MRT), for planaria populations regenerating under continuous exposure to combined DC (78.4 muT) and AC (60.0 Hz at 10.0 muTpeak) magnetic fields applied in parallel was found to be significantly delayed (P << 0.001) by 48 +/- 1 h relative to two different types of control populations (MRT approximately 140 +/- 12 h). One control population was exposed to only the AC component of this field combination, while the other experienced only the ambient geomagnetic field. All measurements were conducted in a low-gradient, low-noise magnetics laboratory under well-maintained temperature conditions. This delay in regeneration was shown to be dependent on the planaria having a fixed orientation with respect to the magnetic field vectors. Results also indicate that this orientation-dependent transduction process does not result from Faraday induction but is consistent with a Ca2+ cyclotron resonance mechanism. Data interpretation also permits the tentative conclusion that the effect results from an inhibition of events at an early stage in the regeneration process before the onset of proliferation and differentiation.

Animals↗

Applied AC and DC magnetic fields cause alterations in the mitotic cycle of early sea urchin embryos.

This study demonstrates that exposure to 60 Hz magnetic fields (3.4-8.8 mT) and magnetic fields over the range DC-600 kHz (2.5-6.5 mT) can alter the early embryonic development of sea urchin embryos by inducing alterations in the timing of the cell cycle. Batches of fertilized eggs were exposed to the fields produced by a coil system. Samples of the continuous cultures were taken and scored for cell division. The times of both the first and second cell divisions were advanced by ELF AC fields and by static fields. The magnitude of the 60 Hz effect appears proportional to the field strength over the range tested. The relationship to field frequency was nonlinear and complex. For certain frequencies above the ELF range, the exposure resulted in a delay of the onset of mitosis. The advance of mitosis was also dependent on the duration of exposure and on the timing of exposure relative to fertilization.

Animals↗