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Additive effects of prostaglandin E2 and pulsed electromagnetic fields on fracture healing.

Bone formation of fractured fibulae stimulated by pulsed electromagnetic fields (PEMF), PGE2, and combination of both was assessed with roentgenography and fluorescent labelling compounds, tetracycline, xylenol orange, and calcein. A total of 72 male New Zealand rabbits was osteotomized by creating a 1 mm-gap at fibulae and randomly divided into 8 groups: one control, one treated with PEMF, three treated with PGE2 of various dosages, and three treated with combined treatments of PEMF and PGE2 of specified dosages. PEMF had positive effects on bone formation. Exogenous PGE2 mimicked the effect of PEMF on linear bone growth. The effect of PGE2 on bone formation or bone remodelling was dose-related (5, 15, 50 micrograms/kg), with 5 micrograms/kg body weight as the optimal dosage in this study. Combination of PEMF and PGE2 exhibited a trend of additive effect on bone formation, especially at 15 micrograms/kg of PGE2. It is hypothesized that PEMF may exert its action on bone healing by increasing the endogenous PGE2. We therefore concluded that external stimulation such as PEMF and PGE2 was beneficial and stimulatory towards bone formation and healing in our animal model. However, the effects were somehow specific in electrical waveforms and dosage. Similar to PEMF, PGE2, therefore, may be a potential agent in promoting bone formation in the clinical treatments of fractures or perhaps non-union.

Animals↗

Cytogenetic effects of pulsing electromagnetic field on human lymphocytes in vitro: chromosome aberrations, sister-chromatid exchanges and cell kinetics.

Exposure of human lymphocyte cultures to a pulsing electromagnetic field (PEMF; 50 Hz, 1.05 mT) for various durations (24, 48 and 72 h) resulted in a statistically significant suppression of mitotic activity and a higher incidence of chromosomal aberrations. Furthermore, the shorter exposure times (24 and 48 h) did not cause a significant delay in cell turnover (cell proliferation index) or an increase in the baseline frequency of sister-chromatid exchanges (SCE). However, cultures continuously exposed to PEMF for 72 h exhibited significant reduction of the cell proliferation index (CPI) and an elevation of SCE rate. These results suggest that exposure to PEMF may induce a type of DNA lesions that lead to chromosomal aberrations and cell death but not to SCE, except probably at longer exposure times.

Adult↗

Effect of pulsing electromagnetic fields on DNA synthesis in mammalian cells in culture.

DNA synthesis in Chinese hamster V79 cells was significantly enhanced when they were exposed to weak, pulsing electromagnetic fields generated by specific combinations of the pulse width (25 microseconds), frequency (10, 100 Hz) and magnetic intensity (2 X 10(-5), 8 X 10(-5) T). Conversely the DNA synthesis of cells in the fields at 4 X 10(-4) T was repressed to 80% of that in controls not exposed to the fields.

Animals↗

Stimulation of protein kinase A activity and induced terminal differentiation of human skin fibroblasts in culture by low-frequency electromagnetic fields.

In the present study experiments are described, which indicate that the exposure of normal human skin fibroblasts (HSFs) to a low-frequency electromagnetic field of 20 Hz and 7-8 mT does induce terminal differentiation within 14 days of daily exposure of 12 h. As demonstrated by the analysis of the expression level of the proto-oncogene c-myc, the induction of terminal differentiation of progenitor fibroblasts to postmitotic fibrocytes does most likely not involve changes in the c-myc protein. As one possible candidate being involved in the ELF-EMF-mediated inhibition of fibroblast growth and the subsequent induction of terminal differentiation the cyclic AMP-dependent protein kinase A (PKA) could be characterised. Thus, the data presented clearly indicate that the specific EMF field of 20 Hz and 7-8 mT significantly interfere with regulatory processes of fibroblast proliferation and differentiation.

Blotting, Northern↗

[Effect of low-intensity electromagnetic fields of industrial frequency on the ultrastructure and proliferative activity of rat's thymus cells].

Effects of two types of low-intensity electromagnetic fields (EMF) of industrial frequency (50 Hz) on the fine structure and proliferative activity of thymic cells in white rats were studied. It was found that a weak EMF with a prevailing electrical component (380-480 V/m, 120-140 nT1) did not affect the DNA synthesis intensity. An EMF with a stronger magnetic induction (10-15 V/m, 800-1500 nT1) diminished the glucose-6-phosphate dehydrogenase activity and proliferative processes in cultured stimulated lymphocytes. Electron microscopic investigation of the thymus after both types of exposure revealed an accumulation of lymphocytes with pyknotic nuclei and electron-dense cytoplasm, as well as hypoplasia of the vascular endothelium. At the same time, EMF with a prevailing magnetic component produced a more marked negative effect on the ultrastructure of thymic cells, which indicated a lowered secretory activity of epitheliocytes.

Animals↗

Extremely low frequency electromagnetic fields as effectors of cellular responses in vitro: possible immune cell activation.

There is presently an intense discussion if electromagnetic field (EMF) exposure has consequences for human health. This include exposure to structures and appliances that emit in the extremely low frequency (ELF) range of the electromagnetic spectrum, as well as emission coming from communication devices using the radiofrequency part of the spectrum. Biological effects of such exposures have been noted frequently, although the implication for specific health effects is not that clear. The basic interaction mechanism(s) between such fields and living matter is unknown. Numerous hypotheses have been suggested, although none is convincingly supported by experimental data. Various cellular components, processes, and systems can be affected by EMF exposure. Since it is unlikely that EMF can induce DNA damage directly, most studies have examined EMF effects on the cell membrane level, general and specific gene expression, and signal transduction pathways. In addition, a large number of studies have been performed regarding cell proliferation, cell cycle regulation, cell differentiation, metabolism, and various physiological characteristics of cells. Although 50/60 Hz EMF do not directly lead to genotoxic effects, it is possible that certain cellular processes altered by exposure to EMF indirectly affect the structure of DNA causing strand breaks and other chromosomal aberrations. The aim of this article is to present a hypothesis of a possible initial cellular event affected by exposure to ELF EMF, an event which is compatible with the multitude of effects observed after exposure. Based on an extensive literature review, we suggest that ELF EMF exposure is able to perform such activation by means of increasing levels of free radicals. Such a general activation is compatible with the diverse nature of observed effects. Free radicals are intermediates in natural processes like mitochondrial metabolism and are also a key feature of phagocytosis. Free radical release is inducible by ionizing radiation or phorbol ester treatment, both leading to genomic instability. EMF might be a stimulus to induce an "activated state" of the cell such as phagocytosis, which then enhances the release of free radicals, in turn leading to genotoxic events. We envisage that EMF exposure can cause both acute and chronic effects that are mediated by increased free radical levels: (1) Direct activation of, for example macrophages (or other cells) by short-term exposure to EMF leads to phagocytosis (or other cell specific responses) and consequently, free radical production. This pathway may be utilized to positively influence certain aspects of the immune response, and could be useful for specific therapeutic applications. (2) EMF-induced macrophage (cell) activation includes direct stimulation of free radical production. (3) An increase in the lifetime of free radicals by EMF leads to persistently elevated free radical concentrations. In general, reactions in which radicals are involved become more frequent, increasing the possibility of DNA damage. (4) Long-term EMF exposure leads to a chronically increased level of free radicals, subsequently causing an inhibition of the effects of the pineal gland hormone melatonin. Taken together, these EMF induced reactions could lead to a higher incidence of DNA damage and therefore, to an increased risk of tumour development. While the effects on melatonin and the extension of the lifetime of radicals can explain the link between EMF exposure and the incidence of for example leukaemia, the two additional mechanisms described here specifically for mouse macrophages, can explain the possible correlation between immune cell system stimulation and EMF exposure.

Animals↗

Exposure of murine cells to pulsed electromagnetic fields rapidly activates the mTOR signaling pathway.

Murine pre-osteoblasts and fibroblast cell lines were used to determine the effect of pulsed electromagnetic field (PEMF) exposure on the production of autocrine growth factors and the activation of early signal transduction pathways. Exposure of pre-osteoblast cells to PEMF minimally increased the amount of secreted TGF-beta after 1 day, but had no significant effects thereafter. PEMF exposure of pre-osteoblast cells also had no effect on the amount of prostaglandin E(2) in the conditioned medium. Exposure of both pre-osteoblasts and fibroblasts to PEMF rapidly activated the mTOR signaling pathway, as evidenced by increased phosphorylation of mTOR, p70 S6 kinase, and the ribosomal protein S6. Inhibition of PI3-kinase activity with the chemical inhibitor LY294002 blocked PEMF-dependent activation of mTOR in both the pre-osteoblast and fibroblast cell lines. These findings suggest that PEMF exposure might function in a manner analogous to soluble growth factors by activating a unique set of signaling pathways, inclusive of the PI-3 kinase/mTOR pathway.

Animals↗

Need for a European approach to the effects of extremely low-frequency electromagnetic fields on cancer. ELF-EMF European Feasibility Study Group.

BACKGROUND: A European feasibility study on environmental exposure to extremely low-frequency electromagnetic fields (ELF-EMF) and cancer was conducted. The study was motivated by public health concern about possible adverse health effects associated with ELF-EMF exposure. METHODS: A review of completed research in Europe was conducted. Information on the methods and accessibility of new epidemiologic studies were requested and reviewed. RESULTS: Eight studies on environmental ELF-EMF exposure have been completed in Europe while 15 large studies are in progress. Although there is no known mechanism by which electric or magnetic fields of this frequency could play a role in the development of cancer or other adverse health effects, the results of the studies conducted so far provide some support for the hypothesis that they are associated with the incidence of childhood leukemia. CONCLUSIONS AND RECOMMENDATIONS: The best use of available data will be made through a pooled re-analysis of data, particularly those on childhood tumors. It is recommended to apply multiple methods for exposure assessment in view of the heterogeneity in the methods used in different studies. New multicenter case-referent studies should not be initiated until the results of the large on-going studies have been reported. Prospective cohort studies will have to be very large to identify moderate excess risks resulting from environmental exposure to ELF-EMF, and their feasibility should be discussed after the results of the on-going case-referent studies have been reported. A European collaborative approach will lead to greater statistical power and will assess the exposure-effect association under differing exposure patterns and distributions of potential confounding factors.

Adult↗

Pulsed electromagnetic fields enhance the induction of cytokines by peripheral blood mononuclear cells challenged with phytohemagglutinin.

We evaluated the effects of a 50-Hz pulsed electromagnetic field on the production of cytokines by both resting and mitogen-treated peripheral blood mononuclear cells. Our results demonstrate that after exposure of normal cells to EMFs for 12 h, the levels of neither interleukin-1beta, nor interleukin-2 were increased. Indeed, the concentration of tumor necrosis factor alpha decreased significantly immediately after the exposure period. The results were, however, markedly different when cells were stimulated with phytohemagglutinin immediately before the exposure to EMFs. In this case the levels of cytokines, measured 24 and 48 h after the treatment, were 630 +/- 440 pg/ml and 910 +/- 530 pg/ml for interleukin-1beta, 530 +/- 330 pg/ml, and 860 +/- 560 pg/ml for tumor necrosis factor alpha, respectively. These values were significantly higher (P < 0.05) when compared with the controls. Interleukin-2 levels were significantly higher at the end of the EMF exposure only in supernatants of phytohemagglutinin-stimulated cells and, as a consequence of this increase, the proliferation indexes also were significantly increased 48 h after the EMFs' treatment. The comparison between biological activity and the cytokine antigen present in our samples indicated that the amount of antigen was paralleled by an equal recovery of biological activity. This suggests either the absence of qualitative differences in these proteins or the impairment of both the transcriptional and translational processes.

Cell Division↗

Effects of pulsed electromagnetic fields on bone healing in a rabbit tibial osteotomy model.

OBJECTIVE: The purpose of this study was to determine the effect of pulsed electromagnetic field (PEMF) exposure on healing tibial osteotomies in New Zealand White rabbits. DESIGN: One-millimeter Gigli saw osteotomies were stabilized by external fixation. One day after surgery, rabbits were randomly assigned to receive either no exposure (sham control) or thirty minutes or sixty minutes per day of low-frequency, low-amplitude PEMF. Radiographs were obtained weekly throughout the study. Rabbits were euthanized at fourteen, twenty-one, or twenty-eight days, and tibiae underwent either destructive torsional testing or histologic analysis. To determine the baseline torsional strength and stiffness of rabbit tibiae, eleven normal intact tibiae were tested to failure. RESULTS: Sixty-minute PEMF-treated osteotomies had significantly higher torsional strength than did sham controls at fourteen and twenty-one days postoperatively. Thirty-minute PEMF-treated osteotomies were significantly stronger than sham controls only after twenty-one days. Normal intact torsional strength was achieved by fourteen days in the sixty-minute PEMF group, by twenty-one days in the thirty-minute PEMF group, and by twenty-eight days in the sham controls. Maximum fracture callus area correlated with the time to reach normal torsional strength. CONCLUSION: In this animal model, low-frequency, low-amplitude PEMF significantly accelerated callus formation and osteotomy healing in a dose-dependent manner.

Animals↗

Combined effects of traffic and electromagnetic fields on the immune system of fertile atopic women.

Object of this preliminary study was the immune response to high or low frequency electromagnetic fields (ELMF) of non-atopic and atopic fertile women with uniform exposure to toxic compounds produced by traffic. Women were divided in group A (non-atopic, non-exposed to ELMF); B (atopic, non-exposed to ELMF); C (non-atopic, exposed to ELMF); D (atopic, exposed to ELMF). "In vitro" cell proliferation of peripheral blood mononuclear cells (PBMC) of atopic women (groups B and D) stimulated by phytohaemoglutinin (PHA) was reduced. The ELMF exposed women (groups C and D) showed lower levels of blood NK CD16(+)-CD56+ lymphocyte subpopulations and of "in vitro" production of interferon-gamma (both spontaneously and in presence of PHA) by PBMC, suggesting that ELMF reduces blood cytotoxic activity. Serum IgE of the atopic women exposed to ELMF (group D) was higher than that of the other groups. Linear discriminant analysis including serum zinc and copper (essential enzymes for immune functions), blood lead and urinary transtrans muconic acid, a metabolite of benzene (markers of exposure to traffic) and key parameters of immune functions (CD16(+)-CD56+ lymphocyte subset, serum IgE, interferon-gamma produced by PBMC in presence of PHA, stimulation index of blastogenesis) showed absence of significant difference between groups A and C and a marked separation of groups B and D. This datum suggests that ELMF have a greater influence on atopic women exposed to traffic than on non-atopic ones.

Adult↗

Neurovegetative disturbances in workers exposed to 50 Hz electromagnetic fields.

OBJECTIVES: Since the circulatory and nervous systems are composed of electrically excitable tissues, it is plausible that they can be stimulated by electromagnetic fields (EMF). No clinical studies have as yet been carried out to explain whether and how occupational exposure to 50 Hz EMF can influence the neurovegetative regulation of the cardiovascular function. The present project was undertaken to assess the autonomic function in workers occupationally exposed to 50 Hz EMF, by analyzing the heart rate variability. MATERIALS AND METHODS: The study group comprised 63 workers of switchyard substations, aged 22-67 years (39.2 +/- 10.0 years), and the control group 42 workers of radio link stations, aged 20-68 years (40.7 +/- 9.2 years), employed at workposts free from EMF exposure. The age range and employment duration in both groups did not differ significantly. To assess the neurovegetative regulation of the cardiac function, heart rate variability (HRV) analysis was made based on 512 normal heart beats recorded at rest. The analysis, performed using fast Fourier transformation, concerned the time- and frequency-domain HRV parameters. Power spectrum in the very low (VLF), low (LF) and high (HF) frequency bands was determined. RESULTS: The relative risk of decreased HRV (STD R-R < 27 ms), calculated with use of a logistic regression model, was significantly higher in the exposed group than in controls (OR = 2.8). The VLF power spectrum was significantly higher in the exposed group and correlated with the exposure level. The percentage of subjects with dominant sympathetic function (LF/HF > 1) was significantly higher in the study group than in controls (65% vs. 47%). CONCLUSIONS: It was concluded that occupational exposure to 50 Hz EMF could influence the neurovegetative regulation of the cardiovascular system.

Adult↗