Effects and molecular mechanisms of the biological action of weak and extremely weak magnetic fields

A number of effects of weak combined (static and alternating) magnetic fields with an alternating component of tens and hundreds nT at a collinear static field of 42 μT, which is equivalent to the geomagnetic field, have been found: activation of fission and regeneration of planarians Dugesia tigrina, inhibition of the growth of the Ehrlich ascites carcinoma in mice, stimulation of the production of the tumor necrosis factor by macrophages, decrease in the protection of chromatin against the action of DNase 1, and enhancement of protein hydrolysis in systems in vivo and in vitro. The frequency and amplitude ranges for the alternating component of weak combined magnetic fields have been determined at which it affects various biological systems. Thus, the optimal amplitude at a frequency of 4.4 Hz is 100 nT (effective value); at a frequency of 16.5 Hz, the range of effective amplitudes is broader, 150–300 nT; and at a frequency of 1 (0.5) Hz, it is 300 nT. The sum of close frequencies (e.g., 16 and 17 Hz) produces a similar biological effect as the product of the modulating (0.5 Hz) and carrying frequencies (16.5 Hz), which is explained by the ratio A = A ₀sinω₁ t + A ₀sinω₂ t = 2A ₀sin(ω₁ + ω₂)t/2cos(ω₁–ω₂)t/2. The efficiency of magnetic signals with pulsations (the sum of close frequencies) is more pronounced than that of sinusoidal frequencies. These data may indicate the presence of several receptors of weak magnetic fields in biological systems and, as a consequence, a higher efficiency of the effect at the simultaneous adjustment to these frequencies by the field. Even with consideration of these facts, the mechanism of the biological action of weak combined magnetic fields remains still poorly understood.     

Effects of low-level combined static and weak low-frequency alternating magnetic fields on cytokine production and tumor development in mice

We investigated the effects of weak combined magnetic fields (MFs) produced by superimposing a constant MF (in the range 30 - 150 µT) and an alternating MF (100 or 200 nT) on cytokine production in healthy Balb/C male mice exposed 2 h daily for 14 days. The alternating magnetic field was a sum of several frequencies (ranging from 2.5 - 17.5 Hz). The frequencies of the alternating magnetic field were calculated formally based on the cyclotron resonance of ions of free amino acids (glutamic and aspartic acids, arginine, lysine, histidine, and tyrosine). The selection of different intensity and frequency combinations of constant and alternating magnetic fields was performed to find the optimal characteristics for cytokine production stimulation in immune cells. MF with a constant component of 60 μT and an alternating component of 100 nT, which was a sum of six frequencies (from 5 to 7 Hz), was found to stimulate the production of tumor necrosis factor-α, interferon-gamma, interleukin-2, and interleukin-3 in healthy mouse cells and induce cytokine accumulation in blood plasma. Then, we studied the effect of this MF on tumor-bearing mice with solid tumors induced by Ehrlich ascite carcinoma cells by observing tumor development processes, including tumor size, mouse survival rate, and average lifespan. Tumor-bearing mice exposed to a combined constant magnetic field of 60 μT and an alternating magnetic field of 100 nT containing six frequencies showed a strong suppression of tumor growth with an increase in survival rate and enhancement of average lifespan.     

Influence of low-intensity magnetic fields on the development of satellite muscle cells of a newborn rat in primary culture

The influence of Earth magnetic field shielded down to 0.3 μT and static magnetic field (60–160 μT) on the proliferation and differentiation of satellite muscle cells in primary culture has been investigated. A stimulatory effect of static magnetic fields on the rate of the formation of massive multinucleate myotubes and an increase in the intracellular calcium concentration ([Ca²⁺] _i ) have been detected for magnetic fields of the microtesla range. On the other hand, it was shown that the reduction of earth magnetic fields to 0.3 μT leads to inhibition of proliferation and differentiation of skeletal muscle cells in primary culture. Since the formation of contractile myotubes during in vitro experiments is similar to the regeneration of skeletal muscle fibers under muscle damage in vivo, it may be concluded that weak magnetic fields have a strong effect on intracellular processes by influencing all phases of muscle fiber formation. It is necessary to take this fact into consideration when forecasting probable complications of skeletal muscle regeneration during long-term exposure of man to low-intensity magnetic fields and also for the potential use of low static magnetic fields as a tool to recover the affected myogenesis.     

Temporally incoherent magnetic fields mitigate the response of biological systems to temporally coherent magnetic fields

We have previously demonstrated that a weak, extremely-low-frequency magnetic field must be coherent for some minimum length of time (≈? 10 s) in order to affect the specific activity of ornithine decarboxylase (ODC) in L929 mouse cells. In this study we explore whether or not the superposition of an incoherent (noise) magnetic field can block the bioeffect of a coherent 60 Hz magnetic field, since the sum of the two fields is incoherent. An experimental test of this idea was conducted using as a biological marker the twofold enhancement of ODC activity found in L929 murine cells after exposure to a 60 Hz, 10 μT_rms magnetic field. We superimposed an incoherent magnetic noise field, containing frequencies from 30 to 90 Hz, whose rms amplitude was comparable to that of the 60 Hz field. Under these conditions the ODC activity observed after exposure was equal to control levels. It is concluded that the superposition of incoherent magnetic fields can block the enhancement of ODC activity by a coherent magnetic field if the strength of the incoherent field is equal to or greater than that of the coherent field. When the superimposed, incoherent noise field was reduced in strength, the enhancement of ODC activity by the coherent field increased. Full ODC enhancement was obtained when the rms value of the applied EM noise was less than one-tenth that of the coherent field. These results are discussed in relation to the question of cellular detection of weak EM fields in the presence of endogenous thermal noise fields. © 1994 Wiley-Liss, Inc.     

Quenching of an electric arc in a vacuum gap with a uniform transverse magnetic field

The breaking ability of a vacuum arc interrupter with a uniform transverse magnetic field formed by a system of permanent magnets was investigated experimentally. The vacuum interrupter with a 0.5-μF shunting capacitor switched off a dc current of up to 150 A at magnetic fields of 100–180 mT. At magnetic fields of 120–160 mT, the breaking ability of the vacuum interrupter was increased to 300 A by introducing a nonuniformity in the magnetic field distribution near the contact surface.     

Magnetic field direction differentially impacts the growth of different cell types

Magnetic resonance imaging (MRI) machines have horizontal or upright static magnetic field (SMF) of 0.1–3 T (Tesla) at sites of patients and operators, but the biological effects of these SMFs still remain elusive. We examined 12 different cell lines, including 5 human solid tumor cell lines, 2 human leukemia cell lines and 4 human non-cancer cell lines, as well as the Chinese hamster ovary cell line. Permanent magnets were used to provide 0.2–1 T SMFs with different magnetic field directions. We found that an upward magnetic field of 0.2–1 T could effectively reduce the cell numbers of all human solid tumor cell lines we tested, but a downward magnetic field mostly had no statistically significant effect. However, the leukemia cells in suspension, which do not have shape-induced anisotropy, were inhibited by both upward and downward magnetic fields. In contrast, the cell numbers of most non-cancer cells were not affected by magnetic fields of all directions. Moreover, the upward magnetic field inhibited GIST-T1 tumor growth in nude mice by 19.3% (p < 0.05) while the downward magnetic field did not produce significant effect. In conclusion, although still lack of mechanistical insights, our results show that different magnetic field directions produce divergent effects on cancer cell numbers as well as tumor growth in mice. This not only verified the safety of SMF exposure related to current MRI machines but also revealed the possible antitumor potential of magnetic field with an upward direction.     

中频交变磁场对大鼠F98胶质瘤细胞的体外生物效应

目的:观察中频交变磁场对大鼠F98胶质瘤细胞增殖能力的影响,初步探讨中频交变磁场抑制肿瘤细胞增殖的生物学机制。方法:体外培养大鼠F98胶质瘤细胞,使其暴露于场强为5 m T的恒定磁场中,并分别加载频率为0、50、100、200、300、400、500、600、700 KHz的不同磁场。磁场暴露24至72小时后,采用MTT法检测细胞增殖、计算抑制率并筛选出抑制胶质瘤细胞生长的最佳磁场频率,应用染色技术和流式细胞术对细胞形态、细胞凋亡、细胞周期进行验证。结果:MTT检测数据表明,100、200、300KHz组细胞增殖抑制率明显高于其他组(P0.05),并且200 KHz组细胞增殖抑制最为显著,抑制率为17%;HE染色显示磁场干预后细胞生长欠佳;Hoechst染色显示细胞核染色质浓缩聚集、核碎裂、核边集,表现出细胞凋亡的典型变化。流式细胞术显示:200 KHz组细胞凋亡率高于对照组(P0.05);各组细胞周期无显著差异。结论:200 KHz的中频交变磁场有抑制大鼠F98胶质瘤细胞增殖的作用,促使肿瘤细胞凋亡,但其具体机制仍待继续研究。     

Effect of weak combined static and extremely low‐frequency alternating magnetic fields on tumor growth in mice inoculated with the Ehrlich ascites carcinoma

It has been shown that the ultralow‐frequency extremely weak alternating component of combined magnetic fields (MFs) exhibits a marked antitumor activity. The parameters of this component have been found (frequency 1, 4.4, 16.5 Hz or the sum of these frequencies; intensity 300, 100, 150–300 nT, respectively) at which this MF in combination with a collinear static MF of 42 µT inhibits or suppresses the growth of Ehrlich ascites carcinoma (EAC) in mice. It was shown that the exposure of mice with EAC to combined MFs causes structural changes in some organs (liver, adrenal glands), which are probably due to the total degradation of the tumor tissue. In mice with transplanted EAC, the tumor tissue after exposure to weak MFs was practically absent, as distinct from control animals in which the invasion of the tumor into the adipose tissue surrounding the kidneys, mesenteric lymph nodes, and spermatic appendages was observed. In animals without tumors, no pathological deviations from the norm in the structure of organs and tissues occurred after exposure to weak MF, indicating that this factor per se is not toxic to the organism. Bioelectromagnetics 30:343–351, 2009. © 2009 Wiley‐Liss, Inc.     

The effect of weak magnetic fields on the production of reactive oxygen species in neutrophils

It was shown that a 1-h-long exposure of mouse peritoneal neutrophils to a combination of a weak constant magnetic field (42 μT) and low-frequency alternating magnetic fields collinear to the weak constant magnetic field (the sum of the frequencies 1.0, 4.4, and 16.5 Hz; amplitude, 0.86 μT) at physiological temperatures caused an increase in the intracellular production of reactive oxygen species, as measured by the changes in fluorescence of the products of 2,7-dichlorodihydrofluorescein and dihydrorhodamine 123 oxidation. The effect of weak magnetic fields was significantly more pronounced in the presence of low concentrations of respiratory burst activators (N-formyl-Met–Leu–Phe or phorbol 12-meristate-13-acetate).

     

Priming of the respiratory burst in neutrophils exposed to a combination of weak constant and alternating low-frequency magnetic fields in vitro

An hour-long exposure of peritoneal neutrophils of mice to a combination of a weak constant magnetic field (42 μT) and low-frequency alternating magnetic fields collinear to the weak constant magnetic field (frequencies 1, 4.4, and 16.5 Hz, total amplitude 0.86 μT) at physiological temperatures promoted a significant increase in chemiluminescence of cells in response to subsequent exposure to low concentrations of respiratory burst activators (formylated peptide N-formyl-Met–Leu–Phe or phorbol ester phorbol-12-myristate-13-acetate) in the presence of luminol. The response of human neutrophils isolated from peripheral blood to the pretreatment with combined magnetic fields followed by exposure to the activator N-formyl-Met–Leu–Phe was similar to the response of mouse neutrophils.     

Effect of Weak Extremely Low Frequency Magnetic Field on Isolated Crayfish Stretch Receptor Neuron: Nonlinear Dependence on Field Amplitude and Frequency

Responses of single mechanoreceptor crayfish neurons to weak extremely low frequency magnetic fields were studied over a wide range of frequencies from 0.001 to 100 Hz, and magnetic fields from 1 to 400 fiT. Observed shifts of neuron impulse activity were weak and variable. They were usually characterized by a slow increase or decrease of spike frequency developing during tens of minutes with markedly variable latencies. Frequency and amplitude “action spectra” were complex, nonlinear, and included several bands (frequency and amplitude “windows”). Neuron response probabilities (if response type and field amplitudes were excluded from consideration) were maximal at 0.001, 0.3, 3, and 60 Hz. They were also maximal at 5, 20, 50, and 300 jaT if field frequencies were not taken into account. Minimal neuron response probabilities were observed at 0.03, 0.8-2, 11-15, and 100 Hz and 1, 10, 30, and 100 /iT, respectively.     

Hydrolysis of various peptides and proteins in weak permanent and low frequency fluctuating magnetic fields

It was shown that weak combined magnetic fields (constant field 25-130 microT; variable field 0.01-0.2 microT; the range of effective frequencies of the alternating component 1-10 Hz) substantially increase the rate of hydrolysis of some proteins and peptides (eight various sequences). The concentration dependence of the dynamics of the process and the dependence of the magnitude of the effect on the parameters of the magnetic field. It was found that: (1) the effect is transmitted through a solvent preliminarily treated by magnetic fields and (2) the effect occurs in the presence of inhibitors of proteases and enzymes inactivating peroxides (catalase and horse radish peroxidase with substrate).     

Combined action of static and alternating magnetic fields on ion motion in a macromolecule: Theoretical aspects

This is an attempt to solve the energetic problem of the primary detection of weak parallel static (DC) and alternating (AC) extremely low frequency (ELF) magnetic fields. We studied the equations of motion for an ion situated inside a macromolecule under the influence of these fields. The main concern is with the magnetic field influence on thermal motion of the ion in the macromolecule. The resonance effects are revealed at discrete frequencies of the ion thermal oscillations determined by the DC field magnitude and the AC field frequency. These phenomena result from the Larmor precession of the ion thermal motion. When the DC field or, to a greater extent, the combined DC and AC fields with the specific frequencies are turned on or cut off, changes occur in the energy of the ion thermal motion. If, inside the macromolecule, the ion is sufficiently protected against immediate impacts of particles of the medium surrounding the macromolecule, these changes may be enough to trigger alteration in the quantum state of the macromolecule. Bioelectromagnetics 19:279–292, 1998. © 1998 Wiley-Liss, Inc.     

Oscillation spectrum of an electron gas with a small density fraction of ions

The problem is solved of the stability of a nonneutral plasma that completely fills a waveguide and consists of magnetized cold electrons and a small density fraction of ions produced by ionization of the atoms of the background gas. The ions are described by an anisotropic distribution function that takes into account the characteristic features of their production in crossed electric and magnetic fields. By solving a set of Vlasov-Poisson equations analytically, a dispersion equation is obtained that is valid over the entire range of allowable electric and magnetic field strengths. The solutions to the dispersion equation for the m = +1 main azimuthal mode are found numerically. The plasma oscillation spectrum consists of the families of Trivelpiece-Gould modes at frequencies equal to the frequencies of oblique Langmuir oscillations Doppler shifted by the electron rotation and also of the families of “modified” ion cyclotron (MIC) modes at frequencies close to the harmonics of the MIC frequency (the frequencies of radial ion oscillations in crossed fields). It is shown that, over a wide range of electric and magnetic field strengths, Trivelpiece-Gould modes have low frequencies and interact with MIC modes. Trivelpiece-Gould modes at frequencies close to the harmonics of the MIC frequency with nonnegative numbers are unstable. The lowest radial Trivelpiece-Gould mode at a frequency close to the zeroth harmonic of the MIC frequency has the fastest growth rate. MIC modes are unstable over a wide range of electric and magnetic field strengths and grow at far slower rates. For a low ion density, a simplified dispersion equation is derived perturbatively that accounts for the nonlocal ion contribution, but, at the same time, has the form of a local dispersion equation for a plasma with a transverse current and anisotropic ions. The solutions to the simplified dispersion equation are obtained analytically. The growth rates of the Trivelpiece-Gould modes and the behavior of the MIC modes agree with those obtained by numerical simulation.     

High-frequency1H NMR studies of the effects of growth factors and phorbol esters on normal syrian hamster diploid fibroblast cells

The nuclear magnetic resonance (NMR) parameters, spin-lattice (T₁), and spin-spin (T₂) relaxation time, are usually longer for neoplastic cells than for normal cells of the same cell type. This has generally been true at low NMR frequencies (≤100 MHz) when comparisons have been made between normal and neoplastic cells that have both spent a short time in culture. We have previously demonstrated that although the T₁ values of paired normal and neoplastic Syrian hamster (SH) fibroblastic cells in culture are not significantly different when measured at 300 MHz, the 300 MHz T₂ values for the neoplastic cells are smaller than those of the normal cells. (Xin et al. (1986),Cell Biophysics 8, 213.) Since treatment of normal diploid cells with polypeptide growth factors or tumor promoters frequently results in reversible expression of neoplasia-associated phenotypes, T₁ and T₂ were obtained at 300 MHz for treated and untreated SH cells to see if these compounds could also produce smaller 300 MHz T₂ values. Secondary culture SH fetal fibroblast cells were treated with epidermal growth factor (EGF), fibroblast growth factor (FGF), phorbol-12,13-didecanoate (PDD) and 4-α-phorbol-12,13-didecanoate (4αPDD). Treatment with either growth factor resulted in smaller T₂ values, but a statistically significant decrease was not observed for PDD or 4αPDD. The observed reductions in T₂ values were correlated with the morphological and growth-stimulatory effects of these compounds on the cells.     

NMR exposure sensitizes tumor cells to apoptosis

NMR technology has dramatically contributed to the revolution of image diagnostic. NMR apparatuses use combinations of microwaves over a homogeneous strong (1 Tesla) static magnetic field. We had previously shown that low intensity (0.3–66 mT) static magnetic fields deeply affect apoptosis in a Ca²⁺ dependent fashion (Fanelli et al., 1999 FASEBJ., 13;95–102). The rationale of the present study is to examine whether exposure to the static magnetic fields of NMR can affect apoptosis induced on reporter tumor cells of haematopoietic origin. The impressive result was the strong increase (1.8–2.5 fold) of damage-induced apoptosis by NMR. This potentiation is due to cytosolic Ca²⁺ overload consequent to NMR-promoted Ca²⁺ influx, since it is prevented by intracellular (BAPTA-AM) and extracellular (EGTA) Ca²⁺ chelation or by inhibition of plasma membrane L-type Ca²⁺ channels. Three-days follow up of treated cultures shows that NMR decrease long term cell survival, thus increasing the efficiency of cytocidal treatments. Importantly, mononuclear white blood cells are not sensitised to apoptosis by NMR, showing that NMR may increase the differential cytotoxicity of antitumor drugs on tumor vs normal cells. This strong, differential potentiating effect of NMR on tumor cell apoptosis may have important implications, being in fact a possible adjuvant for antitumor therapies.     

Characteristics of transverse electric and magnetic field transmission cells at extremely low frequencies

Transverse electric and magnetic field (TEM) cells are often designed to subject samples to electromagnetic radiation of intrinsic impedance (E/H) that is the same as in free space, 377 omega. Earlier work has shown this value to be correct for the RF region above about 2 kHz. In this study, measurements of magnetic fields in the extremely low frequency regions and at DC indicate the E/H ratio to be around 300 omega for frequencies less than 2 kHz in cells of a particular design. This lower value indicates that care should be taken in estimating AC magnetic field intensities from electric field measurements in TEM cells at frequencies below 2 kHz.     

Mechanism of action of combined extremely weak magnetic field on aqueous solution of amino acid

The fundamental physical mechanisms of resonance action of an extremely weak (40 nT) alternating magnetic field at the cyclotron frequency combined with a weak (40 μT) static magnetic field, on living systems are analyzed in the present work. The experimental effects of such sort of magnetic fields were described in different papers: the very narrow resonant peaks in electrical conductivity of the aqueous solutions in the in vitro experiments and the biomedical in vivo effects on living animals of magnetic fields with frequencies tuned to some amino acids. The existing experimental in vitro data had a good repeatability in different laboratories and countries. Unfortunately, for free ions such sort of effects are absolutely impossible because the dimensions of an ion rotation radius should be measured by meters at room temperature and at very low static magnetic fields used in all the above experiments. Even for bound ions these effects should be also absolutely impossible from the positions of classic physics because of rather high viscosity of biological liquid media (blood plasma, cerebrospinal liquid, cytoplasm). Only modern quantum electrodynamics of condensed media opens the new ways for solving these problems. The proposed article is devoted to analysis of quantum mechanisms of these effects.     

Flow sorting of tumor cells for morphometric analysis,particularly of rare cells

Using flow cytometric DNA measurement and sorting combined with morphometric light microscopy, different groups of cells were studied in a human melanoma pleural effusion, a human melanoma lymph node metastasis and a mouse tumor, as well as in normal reference tissues. Beside cells of the predominant tumor cell population, three types of rare tumor cells were studied after enrichment by sorting: a) giant cells from the >8c region, comprising about 5% of the tumor cells, b) binucleated and multinucleated cells with unequal nuclear sizes within the same cell, found at frequencies of about 1.5%, and c) <2c cells which were derived from the so-called “debris”-region of the DNA histogram, found at frequencies of about 1 to 6%. All these rare cells were found only in the malignant tumors and not in the benign reference tissues. Morphometry showed that the increase in the cellular DNA content in the different fractions of tumor cells was combined with an increase in the cellular and nuclear sizes. However, the n/c-ratio was constant in the whole range of tumor cell fractions, including the fractions from the the <2c and the >8c regions. The n/c-ratio of the <2c cells and giant cells differed from that of corresponding normal cells underlining their origin from the predominant tumor cell population. The possible linkage between the occurrence of the three rare cell types and genetic instability of tumors related to faulty nucleus and cell division is discussed.     

Dielectric measurements on live biological materials under magnetic resonance conditions

In the course of work on the interactions of electric and magnetic fields with both living and dead biological materials, it was noticed that certain published dielectrophoretic yield curves for biological cells showed unexplained deviations in the region of 2 kHz. Dielectrophoretic measurements made at frequencies and magnetic fields which satisfied the nuclear magnetic resonance conditions showed sharply resonant features. Dielectric measurements showed small, but sharp, resonances most easily seen in the dielectric loss curves which had a bandwidth of the order of one Hertz and presented at the frequencies which satisfied the magnetic resonance conditions for the ambient magnetic field. Resonances were found corresponding to the frequencies for electron spin resonance and nuclear magnetic resonance for¹H,³¹P,²³Na,³⁷Cl and³⁹K. The onset of these resonances occurs at the value of the steady magnetic field strength so that one quantum of magnetic flux (2.07×10^?15wb) would link a single biological cell or pair of cells, approximately 1 G (100μT) in the case of a 5-μm yeast cell. The effects of these magnetic resonance conditions on the mean generation time ofE. coli and on the reaction of the enzyme lysozyme with the substrateM. lysodeikticus cells are also shown.