Академический Документы
Профессиональный Документы
Культура Документы
1
Department of Chemistry, San Diego State University, San Diego CA 92182 USA.
2
Centro de Graduados e Investigación del Instituto Tecnológico de Tijuana, Apdo postal 1166,
ABSTRACT
Electromagnetic fields (EMFs) played a role in the initiation of living systems, as well as
magnetism. The large numbers of reports on interaction with living systems and the
consequences are presented. An important aspect is involvement with cell signaling and resultant
effects in which numerous signaling pathways participate. Much research has been devoted to
the influence of man-made EMFs, e.g., from cell phones and electrical lines, on human health.
The degree of seriousness is unresolved at present. The relationship of EMFs to reactive oxygen
species (ROS) and oxidative stress (OS) is discussed. There is evidence that indicates a
relationship involving EMFs, ROS and OS with toxic effects. Various articles deal with the
beneficial aspects of AOs in countering the harmful influence from ROS-OS associated with
EMFs. EMFs are useful in medicine, as indicated by healing bone fractures. Beneficial effects
are recorded from electrical treatment of patients with Parkinson’s disease, depression and
cancer.
Correspondence to: Peter Kovacic; Department of Chemistry; San Diego State University; San
1
KEY WORDS
Electromagnetic fields (EMFs), electron transfer (ET), oxidative stress (OS), reactive
INTRODUCTION
Initiation and evolution of life involved chemical compounds and energy sources, such
as the sun and electromagnetism. Bioelectrical phenomena play a vital role in life processes (1).
Among the intrinsic features of living systems are the separation, transport and storage of
electrical charge (2). The participation of electron transfer (ET) is recognized as one of the
Electromagnetic forces are primarily responsible for the structure of matter from atoms to more
complex substances (3) and have played a dominant role in cell division and other processes in
primitive cells as well as modern eukaryotic ones. As expected, electrical effects have been
reported in plant chemistry (4). The preponderance of bioactive substances or their metabolites
incorporate electron transfer (ET) functionalities, which, we believe, play an important role in
physiological responses. The main groups include quinones (or phenolic precursors), metal
complexes (or complexors), aromatic nitro compounds (or reduced nitroso or hydroxylamine
derivatives) and conjugated iminiums (or imines). There are two principal pathways that can
result from ET, one being redox cycling with generation of reactive oxygen species (ROS) and
oxidative stress (OS). The other involves interaction with the central nervous system (CNS).
2
Electron transfer is probably the most prevalent and important process in chemical
transformation. The generality and unifying aspects are demonstrated by involvement in all areas
of the physical and biological sciences. Examples are receptor chemistry (5) and cell-signaling
mechanism (6). Extensive evidence is documented supporting mode of action for carcinogens
CNS, more attention should be devoted to this area, particularly fundamental aspects. A
the feasibility of ET by exogenous and endogenous agents. If the reduction potential is more
positive than -0.5 V, then ET is a possibility in vivo. Requisite electron donors reside mainly in
protein side chains in the form of disulfide, phenolic oxygen, or conjugated amine species.
a variety of areas. The term bioelectrostatics is a label used in the life science area in which
Subjects addressed are enzymes, membranes, chromosomes, histamine, receptors, the Hofmeister
effect, plant chemistry and evolutionary development. A recent hypothesis proposes that
potential (MEP) associated with ions and dipoles (5). Energetics and bridging may be important
actors.
discussed (15). A hypothesis was presented for the basic mode of action of phosphates and
sulfates in cell signaling, with phosphorylation being the center of attention. In both cases, the
anions provide strong electrostatic fields that are believed to be of major importance. It is
3
probably not coincidental that the phosphates involved are mono- or di-esters containing at least
one free hydroxy group in anion form. A similar situation pertains to sulfation in which
monoesterification preserves an anion residue. The field may serve as a link that connects
The cell is able to couple the energy of ATP hydrolysis directly to endergonic processes
by transferring a phosphate from ATP to some other molecule, which then becomes more
reactive [15,16]. Nearly all cellular work depends on energizing by ATP of other molecules via
transfer of phosphate. This situation may apply to phosphate insertion by ATP into signaling
Reports on electrochemical effects of metal cations mainly involve Mg, Zn, Fe, Ca, and
Cu (17). Of these, calcium has received the most attention in relation to cell communication and
receptor binding. Calcium and other alkaline earth cations change the electrostatic potential
adjacent to negatively charged bilayer membranes. Organic cations, such as dimethonium, were
Electromagnetic phenomena are associated with charged radicals and electrons in motion.
Although this idea has been advanced previously, it has attracted little attention. A crude
hypothesis for ET involvement in neurotransmission was advanced in 1983. Two years later,
electron translocation brought about by redox reactions was visualized as being the primary
mechanism whereby electric fields are generated in the living cell (18). Fast movement of
conceivably progresses by means of radical intermediates. In 1996, the ET concept was applied
4
A 2004 review summarizes the present status of electrophysiological effects, and
deserves special attention (21). After a burst of research dealing with electrical coupling, gap
junctions became less popular among neurobiologists vs. the ionic approach. Recent reports have
brought gap junction back into the spotlight, suggesting that this type of cell-cell signaling may
Besides the trivial primary effects of electromagnetic fields (EMF) on ionic charges and
dipolar matter, cellular biochemical reaction and channel transport processes are field dependent
(22). Interaction of signaling systems with low energy EMFs may produce metabolic responses
in the body (23). The applied field might modify existing signal transduction processes in cell
membranes, thus producing both transduction and biochemical amplification of the existing field
effects. A practical example comprises the physiological effects of the external field in the
electrostatics (5). At clinically relevant concentrations, ethers, alkyl halides and alcohols
enhance agonist action on the GABA (A) receptor, whereas alkanes do not. A good correlation
exists between dipole moments and receptor activity. Dipole moments are related to
Electrostatic forces are relatively weak. Can such low levels have an influence in living
systems? A recent study provides evidence for involvement. Investigators have gained insight
into physiological events in which weak forces, as low as 0.5 picoNewtons, play a regulatory
role e.g., in ion channel functioning (25). It is fascinating that at the cellular level, weak forces
may be more important than strong ones. Weak magnetic forces that operate over short distances
are associated with prevalent radicals. Mounting evidence indicates that energy is a significant
5
factor in electrostatic operation (4). Support is available from studies in a variety of fields both
Living creatures can be regarded as complex electrochemical systems that evolved over
billions of years (6). Organisms interact with and adapted to an environment of electrical and
magnetic fields. Humans are now immersed in a man-made environment of such fields whose
copper, the metal serves as conduit for electrons. The electrical energy is converted into a useful
end result. Electrons and holes are also involved in semi-conductor operation. Other examples
The present review deals with electromagnetism in biological systems and in medicine.
The electrochemical aspects are updated. The magnetic portion is also the center of attention.
The approach is in an integrated manner involving general aspects, cell signaling, electron
transfer, electromagnetic effects, radicals, oxidative stress and antioxidants. Various toxic
manifestations are addressed, as with brain illnesses, electrical power lines and cell phones. A
agents is often complex and multifaceted. There is greater need of interdisciplinary approaches
of the type in this review. Knowledge of events at the basic molecular level can result in practical
is not included in depth in the major topics. In some cases, original references are present in the
reviews or articles.
6
A number of articles present a broad view of the effects of electromagnetic fields
(EMFs) on living systems. Magnetic fields (MF) are widely distributed in the environment and
their effects are increasing with burgeoning development of electrical machines. It has been
suggested that EMF, especially weak ones, may affect various functions of living things and
several experiments to evaluate the idea have been carried out (26). Studies in cell biology have
demonstrated that weak EMF can affect various cellular functions and important EMF targets in
cells are signal transduction cascades. Furthermore, EMF affects not only specific gene
transcription and cell growth, but also membrane mediated signal transduction processes,
especially the Ca2+ transport system. Effects of MF on mitochondrial functions, cell growth and
transformation, signal transduction of neutrophils, cell apoptosis, gene expression and lipid
It is now well established that low frequency (<300 Hz) EMF fields induce
biological changes that include effects ranging from increased enzyme reaction rates to increased
transcript levels for specific genes (27). The induction of stress gene HSP70 expression by
exposure to EMF provides insight into how these fields interact with cells and tissues. The large
amount of published data available on the heat-induced stress response (i.e., ‘heat shock’) offers
a model for studying and comparing the EMF-induced stress response. Results from these and
other studies have yielded important clues to EMF interaction with cellular systems, particularly
Insight into the mechanism(s) are also provided by examination of the interaction of
EMF with moving charges and their influence on enzyme reaction rates in cell-free systems. In
general, biological studies with in vitro model systems have focused on the nature of the signal
7
transduction pathways involved in response to EMF. Based on evidence of the electron
transport/charge flow in DNA, it is likely that EMF interact directly with electrons in DNA to
stimulate biosynthesis.
Studies of EMF induction of the stress response proteins, point to the application of
EM fields in two biomedical applications: cytoprotection and gene therapy. Therapeutic use of
EMFs has met with great success since the early 1970’s in accelerating the healing of bone
Paradoxically, it is the health risk issue that has in recent years dominated EMF
research. Epidemiological studies have indicated that EMFs can also induce health adverse
effects and EMF are perceived by biological systems as a possible hazard. However, exposure to
EMFs also has beneficial effects (28), as understanding of mechanisms expands. Specific
requirements for field energies are being defined and the range of treatable ills broadened. These
include nerve regeneration, wound healing, graft behavior, diabetes, and myocardial and cerebral
Life on earth has evolved in a sea of natural EMFs. Over the past century, this natural
environment has sharply changed with introduction of a vast and growing spectrum of man-made
EMFs (29). From models based on equilibrium thermodynamics and thermal effects, these fields
were initially considered too weak to interact with biomolecular systems, and thus incapable of
influencing physiological functions. Laboratory studies have tested a spectrum of EMF fields for
bioeffects at cell and molecular levels. Modulation of cell surface chemical events by EMFs
indicates a major amplification of initial weak effects is associated with binding of hormones,
antibodies, and neurotransmitters to their specific sites. Calcium ions play a key role in this
8
In cellular aggregates that form tissues of higher animals, cells are separated by
narrow fluid channels that take on special importance in signaling from cell to cell. These
channels act as windows on the electrochemical world surrounding each cell. Hormones,
antibodies, neurotransmitters and chemical cancer promoters, for example, move along them to
reach binding sites on cell membrane receptors. These narrow fluid “gutters,” typically not more
than 150 A wide, are also preferred pathways for intrinsic and environmental EMFs, since they
offer much lower electrical impedance than cell membranes. Although this intercellular space
(ICS) forms only about 10% of the conducting cross section of typical tissue, it carries at least
90% of any imposed or intrinsic current, directing it along cell membrane surfaces. Numerous
stranded protein molecules protrude from within the cell into this narrow ICS. Their glycoprotein
tips form the glycocalyx, which senses chemical and electrical signals in surrounding fluid. Their
negatively charged tips form receptor sites for hormones, antibodies, neurotransmitters, and for
many metabolic agents, including cancer promoters. These charged terminals form an anatomical
substrate for the first detection of weak electrochemical oscillations in pericellular fluid,
environmental fields.
If one used electromagnetic energy sensors to view the world from space 100 years ago,
the world would have looked quite dim (30). Now the world glows with electromagnetic energy
emissions at the nonionizing portion of the spectrum, such as power line fields, radio waves,
microwaves, etc.
Living organisms are complex electrochemical systems that evolved over billions of
years in a world with relatively simple weak magnetic field and with few EM energy emitters.
As is characteristic of living organisms, they interact with and adapted to this environment of
9
electric and magnetic fields. One example of this adaptation is the visual system, which is
exquisitely sensitive to emissions in the very narrow portion of the EM spectrum that we call
light. Organisms also adapt to another portion of the spectrum, the UV, by developing filtering
systems in the eye and the skin to protect them from it.
regulate various critical cellular systems; we see this in the complex of circadian rhythms. Fish,
birds, and the duckbill platypus developed systems to use electromagnetic fields to sense prey
and to navigate. EM fields are involved in neural membrane function. Even protein conformation
Thus, it is not surprising that massive introduction of EMF in an enormous range of new
frequencies, modulations, and intensities in recent years have affected living organisms. In fact,
it would be incredible and beyond belief if these EMF did not affect the electrochemical systems
extremely low-frequency EMF to which populations are exposed; these human- made fields are
substantially above the naturally occurring ambient electric and magnetic fields of ~10-4 Vm-1
and ~10-13 T, respectively (31). Several epidemiology studies have concluded that low frequency
EMF may be linked to an increased risk of cancer, particularly childhood leukemia. These
biological systems, most notably on the activity of components of the pathways that regulate cell
proliferation. However, the limited number of attempts to directly replicate these experimental
findings have been almost uniformly unsuccessful, and no EMF-induced biological response has
yet been replicated in independent laboratories. Many of the most well-defined effects have
10
come from gene expression studies; several attempts have been made recently to repeat these
findings. This review analyzes these studies and summarizes other reports of major cellular
Geomagnetic fields can serve as the combined magnetic field, affecting different
biochemical ions in cells (32). Also influenced are electrostatic processes including phosphate
group transfer. Ligand-receptor effects can be due to field influence on substances abundant in
the cell, as well as on molecules participating in intracellular signaling and membrane transport
whose perturbation can be amplified by enzyme cascades or ion fluxes. Weak extremely low-
A recent review concentrates on findings described in the recent literature on the response
of cells and tissues to EMFs (33). Models of the interaction between different forms of EMF and
ions, biomolecules in the cell and cell surface recognition are discussed. Naturally occurring
electric fields are not only important for cell-surface interactions, but are also pivotal for the
normal development of the organism and its physiological functions. The review also bridges the
gap between recent cell biological studies (EMF actions) and aspects of EMF-based therapy,
OS
A study demonstrated the effects of 900 MHz EMF emitted from cellular phone on
brain tissues and also blood malondialdehyde, glutathione, retinol, vitamin D3, tocopherol and
catalase enzyme activity of guinea pigs (34). Results indicated production of OS in brain tissue.
A similar study showed 900 MHz mobile phone-induced oxidative endometrial impairment (35).
The modulation of OS with vitamin E and C reduces the endometrial damage, both at
biochemical and histological levels. Similar exposure also enhanced lipid peroxidation and H2O2
11
content accompanied by diminished antioxidative enzyme activity, indicating OS could be partly
due to reduced activities of AO enzymes in duckweed (36). Rats exposed to EMF showed
increase in malondialdehyde levels and decrease in GSH levels (37). A study demonstrated
protective effects of melatonin and caffeic acid phenethyl ester (CAPE) against retinal oxidative
stress in long-term use of mobile phone (38). Mobile phone-induced myocardial OS protection
by the AO CAPE was shown (39). CAPE may prevent the 900 MHz EMF-induced oxidative
changes in liver by ROS reducing and increasing AO enzyme activities (40). Radiofrequency
electromagnetic radiation from mobile phones induces OS and reduces sperm motility in rats
(41). Thus, semen quality and male fertility may be negatively affected. The protective effects
OS was reported (42). Results indicate significant increase in the levels of oxidative products
e.g., malondialdehyde, and significant decrease in the AO enzyme SOD; GSH-Px activity was
affected on exposure to EMF. Addition of AOs resulted in the reduction of OS prior to EMF
application.
cancer in vitro (43). Apoptosis together with cell cycle arrest were the dominant causes of the
MF-elicited cell growth inhibition, mediated by MF-induced ROS. These results suggest
possibility of using 60-Hz MF in radiation therapy of prostate cancer. There is formation of ROS
in cells after exposure to 900 MHz radio frequency radiation (44). Results showed that hydrogen
of the influence of heat and thermoacoustic waves (45). The induction of intracellular ROS by
blue light implies that redox effects may mediate the cellular responses. This result suggests the
12
opportunity to mitigate any effects of direct or coincident exposure during dental treatment via
AO (46). A recent study suggests that 872 MHz RF radiation might enhance chemically induced
ANTIOXIDANTS (AOs)
A study suggests that mobile telephone radiation leads to oxidative stress in corneal
and lens tissues and the AOs, such as vitamin C, can help to prevent these effects (48). Mobile
carbonyl groups, xanthine oxidase activity and decreasing catalase activity, and that treatment
with melatonin significantly prevented oxidative damage in the brain (49). Increase in
malondialdehyde levels of renal tissue and also the decrease in renal SOD, catalase, GSH
peroxidase activities demonstrate the role of OS induced by mobile phone exposure. Melatonin,
via its free radical scavenging and AO properties, ameliorated oxidative tissue injury in rat
kidney (50). A similar study suggested that EMF at the frequency generated by a cell phone
causes OS and peroxidation in the ertythrocytes and kidney tissues from rats. In the erythrocytes,
vitamin C seems to protect against the OS (51). A citrus flavoglycoside, naringin protects mouse
liver and intestine against the radiation-induced damage by elevating the AO status and reducing
signaling and activated JNK-apoptotic signaling in Dorsophila (53). Near infrared increased
ROS production independent of ischemia and reperfusion, and this effect was blocked by N-
13
decreasing the motility and vitality of these cells while stimulating DNA base adduct formation
and, ultimately DNA fragmentation. These findings have clear implications for the safety of
extensive mobile phone use by males of reproductive age, potentially affecting both their fertility
and health, as well as wellbeing of their offspring (55). There is ample evidence that
radiofrequency-electromagnetic radiation can alter the genetic material of exposed cells in vivo
and in vitro and in more than one way (56). This genotoxic action may be mediated by
DNA-repair mechanisms. A study showed the gene expression of rat neuron could be altered by
exposure to radio frequency EMF under experimental conditions (57). EMF is a stressor agent
that induces an imbalance between ROS generation and AO defense response (58). Calcium ions
may play a pivotal role in enhancing OS, pro-inflammatory reactions and apoptosis associated
CELL SIGNALING
Interaction with signaling systems is a potential mechanism by which very low-energy EMfs
might produce metabolic responses in the body (59). Hormone and neurotransmitter receptors
are specialized protein molecules that use a variety of biochemical processes to pass chemical
signals from the outside of a cell across the plasma membrane to the interior. Since many low-
energy EMFs have too little energy to directly traverse the membrane, it is possible that they
may modify the existing signal transduction process in cell membranes, thus providing both
transduction and biochemical amplification of the effects of the field itself. As an example, one
metabolic process in which the physiological effects of low-energy EMFs is well established in
the healing of bone fractures. The process of regulation of bone turnover and healing is reviewed
14
in the context of clinical applications of electromagnetic energy to the healing process. A
hypothetical molecular mechanism is presented that might account for the observed effects of
EMF on bone cell metabolism in terms of the field interference with signal transduction events
There are miscellaneous, additional articles dealing with cell signaling. Exposure of
murine cells to pulsed EMFs rapidly activates the mTOR signaling pathway (60). These findings
suggest that pulsed EMF exposure might function in a manner analogous to soluble growth
factors by activating a unique set of signaling pathways. A recent study reported that pulsed
EMF treatment of osteoblastic cells stimulated the rapid phosphorylation of the mammalian
target rapamycin and its downstream mediators (61). Exposure to 900 MHz EMF induces an
unbalance between pro-apoptotic and pro-survival signals in leukemia cells (62). Pulsed electric
fields with long durations can induce cell fusion or introduce xenomolecules into cells (63). As
the pulse duration decreased, plasma membrane electroporation decreased and appearance of
apoptosis markers were delayed. The results suggest that with decreasing pulse durations,
nanosecond pulsed electric fields modulate cell signaling from plasma membrane to intracellular
structures and functions. Injection of electric field pulses of high intensity and short duration
increases the membrane permeability due to reversible electrical breakdown of the cell
membrane. Such pulses lead to apoptosis in Jurkat T-lymphoblasts and in HL-60 cells including
Studies with human hematopoietic cell line TF-1 suggest multifarious effects of EMF
on lipid signal transduction, with doses of 30 or 40 pulses having an anti-proliferative effect (65).
Changes in the lipid second messengers and shift in some molecular species, such as phosphates,
were observed. Static magnetic field on normal human neuronal cell culture induced dramatic
15
changes of morphology, formed vortex of cells and exposed branched neuritis featuring synaptic
buttons (66). Inositol lipid signaling was significantly reduced. Endothelin-1 release from FNC-
B4 cells was also dramatically reduced. Results suggest fields below 0.5T have significant
Various reports show interaction of EMF and tyrosine kinase. Exposure of lymphoma
cells to low energy EMF results in tyrosine kinase-dependent activation of phospholipase leading
to increased inositol phospholipids turnover (67). Exposure of human skin fibroblasts and rat
osteoblasts to extremely low-frequency EMF induced increase in protein kinase activity (68). A
similar study showed extremely low frequency magnetic fields initiate protein tyrosine
phosphorylation of the T cell receptor complex (69). Findings are in line with earlier reports on
how magnetic field exposure affects signal transduction in Jurkat. In a related study it was shown
that extremely low frequency magnetic fields alter the intracellular calcium concentrations in the
demonstrate that weak EMFs can elicit in vivo and in vitro bioeffects from several different
biological systems (71). Of particular interest are those studies that report the existence of
frequency of EMF. The significance of DC magnetic fields for “window” or “resonance” effects
was pointed out two decades ago. The importance of weak EMF bioeffects is now well
activities triggered by ligand-gated binding of hormones, antigen molecules, growth factor and
other cell surface agonists which are key pathways for the activation, differentiation and
proliferation of many cell types. Calcium ions appear to be essential in the first steps of
16
transduction coupling of exogenous physical signals at the cell membrane and in the ensuing
calcium signaling by EMF has, thus, been suggested to be a plausible candidate for activation of
a number of biochemical reactions. EMF coupling with cellular targets may occur via highly
cooperative steps. For example, calcium-dependent steps in the target pathway may include: (i)
initial detection of EMF with resultant electrochemical changes at specific binding sites; (ii)
membrane bound proteins signaling to the cell interior; (iii) EMF coupling with the cytoskeleton
lymphocytes exposed to a magnetic field (72), providing evidence for an electric field metric and
site of interaction involving the calcium ion channel. A similar study showed a membrane
mediated Ca2+ signaling process is involved in the mediation of EMF in the immune system (73).
High frequency (900 MHz) low amplitude (5 Vm-1) electromagnetic field stimulus affects
transcription, translation, calcium and energy charge in tomato (74). Within minutes of exposure
kinase inhibitor) accumulated in a rapid, large and 3-phase manner typical of an environmental
stress response. Extremely low frequency, time-varying fields act in combination with static
magnetic fields to alter calcium signaling in the lymphocytes (75) and inhibits calcium influx
signaling and exhibit field response. The interaction of low intensity magnetic field predicts the
occurrence of biological effects at specific values for the frequency and field intensity of the
EMF and static magnetic fields. In a similar study calcium influx was elevated 1.5-fold when
lymphocytes were exposed to Con-A plus magnetic field (76). The signal transduction
17
hypothesis is supported by experimental evidence for a general biological framework for
understanding magnetic field interactions with the cell through signal transduction. Magnetic
changes in lymphocytes, such as calcium influx and c-MYC mRNA induction, were not
triggered by weak mitogenic signal unless accompanied by a magnetic field. Thus, magnetic
fields have the ability to potentiate or amplify cell signaling. In a study using radioactive 45Ca2+
and murine leukemia cell line, significant increase of calcium influx was shown when exposed to
EMF (77).
promoting phorbol ester on protein kinase C and cell cycle in human cells was carried out;
results indicated lower concentration of phorbol ester induces a less maximum effect on PKC
induced shape changes in invertebrate immunocytes and the activation of an alternative “stress
pathway” were discussed (79). Exposure of Mytilus galloprovincialis to magnetic fields in the
of immunocytes. An intensity of 200 μT was ineffective, while 300 and 400 μT provoked a
temporary damage, and above this level damage progressively became permanent.
The fundamental mechanistic aspects of cell signaling have been addressed (80).
mobile phones induces the activation of the extracellular-signal regulated kinase cascade and
how it induces transcription and other cellular processes were described (81). Upon irradiation
18
(mobile phone frequencies) on MAPK cascades and ERKs are rapidly activated in response to
various frequencies and intensities of EMF. The first step is mediated in the plasma membrane
by NADH oxidase, which rapidly generates ROS. These ROS then directly stimulate matrix
metalloproteinases and allow them to cleave and release heparin-binding epidermal growth
factor, which, in turn, further activates the extracellular-signal regulated kinase cascade. Mobile
phone radiation-induced activation of hsp27 may (i) facilitate the development of brain cancer by
inhibiting the cytochrome c/caspase-3 apoptotic pathway and (ii) cause an increase in blood
brain barrier permeability through stabilization of endothelial cell stress fibers (82). Authors
postulate that these events, when occurring repeatedly over a long period of time, might become
a health hazard because of the possible accumulation of brain tissue damage. Furthermore, other
BONE REPAIR
Appreciable attention has been paid to the practical, medical effects of electrical field
exposure on bone injury. There has been renewed interest in the use of magnets for enhancing
tooth movements (83). The major premise upon which magnetic effects alter cell reactions is
based upon electrically based theories of cellular signaling or perturbation of polar proteins
within the cell membrane. The two major theories are based upon electrically based phenomena,
Both mechanical and electrical signals have been shown to regulate the synthesis of
extracellular matrix and may do so through the stimulation of signaling pathways at the cell
nucleotides (84). The therapeutic use of electric fields is derived from the observation that when
bones are placed under mechanical load (stress) the deformation (strain) is accompanied by an
19
electrical signal and the signal is related to strain characteristics. This strain-related or
straingenerated electric potential has been hypothesized to consist of information transfer to the
osteocyte regarding the nature of its mechanical environment and the state of the extracellular
matrix. The origin of the electric signal was thought initially to be related to defamation of the
crystalline structure of extracellular matrix collagen, involving the piezoelectric effect. Other
data, however, have suggested that alterations in fluid flow might produce electrokinetic events,
specifically streaming potentials, which might be partly or wholly responsible for the observed
electric potential.
There are different transduction pathways for ultrasound and pulsed electromagnetic
field stimulation that lead to an upgrade of osteoblast proliferation, with their pathways all
leading to an increase in cytocolic Ca2+ and activation of calmodulin (85). These findings offer a
biochemical mechanism to support the process of ultrasound and pulsed electromagnetic field-
Pulsed EMFs affect phenotype and connexin 43 protein expression (86). The mechanism
by which EMFs affect bone turnover are unclear. They can directly affect osteoclastic cells, and
there is evidence that cells in the osteoblast lineage are sensitive to EMFs. Pulsed EMF can
influence MG63 osteoblst-like cells by increasing transforming growth factor beta-1 (TGF- 1),
levels but decreasing levels of prostaglandin E2 (PGE2) in the conditioned media. Pulsed EMFs
also increase TGF- 1 production by atrophic and hypertrophic nonunion cells. Others have
MISCELLANEOUS
(87). Furthermore, a significant increase in superoxide production after exposure to EMF was
20
detected. Extremely low frequency EMF can partially block the differentiation of Friend
erythroleukemia cells, and this results in a larger population of cells remaining in the
interfaces was studied (89). The specific ligand-binding sites are generally flanked by basic
Biophysical input, including electric and EMFs, regulate the expression of genes in
connective tissues for structural extracellular matrix proteins resulting in an increase in cartilage
and bone production (90). Electric and EMF increase gene expression for, and synthesis of,
growth factors and this may function to amplify field effects through autocrine and paracrine
signaling. Electric and EMFs can produce a sustained upregulation of growth factors, which
eukaryotic proteins, also suggesting possible biological effects in living cells (91). Moreover, it
has been demonstrated that prolonged exposure to low-intensity microwave fields can induce
heat-shock responses.
EMFs affect transcript levels of apoptosis related genes in embryonic neural cells
(92). EMF exposure of neural progenitor cells transiently affects the transcript level of genes
tumors, particularly astrocytomas (93). For example a study revealed more risk of brain tumors
21
study, particularly compelling, showed employment in occupations that entail exposure to EMF
presents an elevated risk of 1.7 for all gliomas, and a risk of 10.3 for astrocytomas. Though a
recent study did not support the hypothesis of an increased risk of brain cancer associated with
there is a small, pervasive association between brain cancer and exposure to EMF. The biological
basis for such association, i.e., the cellular and molecular mechanisms underlying these effects of
A prevailing hypothesis is that EMF may not cause cancer initiation, but may instead
act as a promoter (93). Several studies suggest possible mechanisms to explain the association
between EMF exposure and cancer. One of the most interesting and unifying hypotheses
involving interaction of EMF with signal transduction systems. Specifically, EMF may influence
the signal transduction cascade at the level of the cell membrane, trigger changes in calcium
influx and/or receptor binding, and induce gene expression and protein synthesis, which may
ultimately lead to cell proliferation. Preliminary evidence also suggests that exposure to EMF
causes an increase in protein kinase C activity. PKC is recognized as a key component of the
cellular signal transduction cascade and has been implicated in modulating the expression of
Ca2+ influx (94). The rescue of damaged cells may be the mechanism explaining why magnetic
fields that are not mutagenic per se are often able to increase mutation and tumor frequencies.
EMF exposure have reported both decreased and increased susceptibility (95). Interestingly,
previous studies involving DNA repair and EMF exposure have reported no effect.
22
The interaction of static magnetic fields (SMFs) with living organisms is a rapidly
growing field of investigation (96). However, despite an increasing number of studies on the
effects of the interaction of SMFs with living organisms, many gaps in our knowledge still
remain. One reason why it is extremely important to understand the mode of action of magnetic
fields on living organisms, is the need to protect human health in consideration of the increasing
introduction of new technologies, such as magnetically levitated trains and the therapeutical use
of magnetic fields( e.g., magnetic resonance imaging ( MRI), coupling of magnetic field
SMFs on different cell types, by means of light and electron microscopy, confocal laser scanning
microscopy and immuno- or cytochemistry (96). The morphological modifications related to cell
shape, cell surface, cytoskeleton, and plasma membrane expression of molecules and
apoptotic cells in primary cell cultures were studied. Results showed moderate-intensity (6 mT)
SMFs induced modifications of cell shape, cell surface and cytoskeleton. Apoptosis was
Several physical mechanisms have been proposed to account for the initial
interactions with cells (97). Magnetic fields interact with moving charges in cells and change
their velocities, as in the classic interaction of magnetic field with any moving charge. Charge
flow associated with a biological function, as for enzyme activity, has been demonstrated in Na,
23
Interaction of weak EMF with living cells is a most important, but unresolved
biophysical problem (98). Regulation of ion and substrate pathways through microvilli provides
a possible theoretical basis for the comprehension of physiological effects of even extremely low
magnetic fields.
Erythroleukemia K562 cells and lentil root protoplasts have been subjected to pore-
forming electric fields suitable for transfection experiments (99). Evidence showed the amount
enhancement of membrane permeability and was associated with greater membrane fluidity.
The membrane hydroperoxides formed upon electric shock enhanced cell luminescence, and
[100]. Electrical signaling is involved with changes in membrane potential and electrical
impulses in nerve cells for use in communication with other cells. The process entails conversion
of electrical signals into chemical ones. There is knowledge of phosphorylations that affects
There is speculation that biomolecular radicals are the basis for a magnetosensitive
compass that guides migrating birds. The magnetosensitivity of photo-induced radical pairs serve
as a probe of protein substrate interactions [101]. The technique, involving a weak magnet, may
be used to gain information on molecular dynamics, diffusion on surface, charge interactions and
surface potentials.
A novel hypothesis about visual perception and imagery has been proposed recently,
which states that external electromagnetic visible photons are converted into electrical signals in
24
the retina and are then conveyed to the V1 area (102). These electrical signals can be converted
subsequently to bioluminescent photon signals. There is a role for ROS and reactive nitrogen
species.
Very complex magnetic fields rotating around and within the brain can interact with
interaction (104). The literature provides related studies involving magnetic stimulation (105-
110).
Various studies are reported on electrical therapy for Parkinson’s disease. Rapid electrical
stimulation is safe and efficient in treatment of patients (111, 112). The literature contains similar
obtained good outcomes with high safety and tolerability (115). There is evidence for electrical
nerve stimulation as the treatment of choice for pain and depression (116). Another investigation
deals with the influence of transcranial current stimulation coupled with repetitive electrical
treatment of cancer (118, 119). Gold nanoparticles efficiently convert the absorbed light into
localized heat which can be exploited for the selective laser photothermal therapy of cancer
(120).
There are recent articles dealing with electric and EMFs that regulate extracellular
matrix synthesis and stimulate repair of fractures and nonunions (121). The study suggests that
25
exposure to EMFs can accomplish the following: 1) regulate proteoglycan and collagen synthesis
formation and repair, 3) increase union rates in fractures and 4) produce results equivalent to
bone grafts. Chang et al. demonstrated that pulsed EMF with different intensities could regulate
stimulating factor in marrow culture system (122). A clinical study with 64 patients undergoing
hindfoot arthrodesis (144 joints) showed, if all parameters are equal, the adjunctive use of pulsed
EMF increases the rate and speed of radiographic union of joints (123). A similar study with 100
patients with symptomatic pseudarthrosis lumber spine fusion, pulsed EMF was shown to be an
CONCLUSION
medicine. However, many workers in these areas have little knowledge of the subject and its
importance. This review documents the many interactions of electromagnetic fields (EMFs) with
biological systems and the consequences. Cell signaling has been the subject of much attention
oxygen species and oxidative stress, which may lead to toxicity and high levels of the harmful
radicals. The unresolved question of danger associated with man-made EMFs is included.
Beneficial effects of EMFs are discussed, such as in the healing of bone fracture, Parkinson’s
ACKNOWLEDGMENT
REFERENCE
26
1. Kovacic P, Hall ME. Bioelectrochemistry, reactive oxygen species, receptors and cell
5. Kovacic P, Pozos RS, Draskovich CD. Unifying electrostatic mechanism for receptor-
6. Kovacic P, Pozos RS. Cell signaling (mechanism and reproductive toxicity): redox
mitochondrial uncouplers, inhibitors, and toxins: focus on electron transfer, free radicals,
9. Kovacic P, Jacintho JD. Reproductive toxins: pervasive theme of oxidative stress and
27
11. Kovacic P, Somanathan R. Integrated approach to immunotoxicity: electron transfer,
reactive oxygen species, antioxidants, cell signaling, and receptors. J Recept Signal
oxidative stress and protection by antioxidants. Curr Med Chem - CNS Agents 2005, 5,
249-258.
13. Kovacic P, Somanathan R. Ototoxicity and noise trauma: electron transfer, reactive
oxygen species, cell signaling, electrical effects, and protection by antioxidants: practical
14. Kovacic P, Thurn LA. Cardiovascular toxicity from the perspective of oxidative stress,
electron transfer, and prevention by antioxidants. Curr Vasc Pharmacol 2005, 3, 107-117.
15. Kovacic P, Draskovich CD, Pozos RS. Unifying electrostatic mechanism for phosphates
and sulfates in cell signaling. J Recept Signal Transduct Res 2007, 27, 433-443.
17. Kovacic P. Unifying electrostatic mechanism for metal cations in receptors and cell
19. Kovacic P. Electron transfer mechanism for regulatory action by nitric oxide.
28
20. Jacintho JD, Kovacic P. Neurotransmission and neurotoxicity by nitric oxide,
catecholamines, and glutamate: unifying themes of reactive oxygen species and electron
synapses: a dynamic signaling system that shapes the activity of neuronal networks.
52, 43-49.
23. Luben RA. Effects of low-energy electromagnetic fields (pulsed and DC) on membrane
signal transduction processes in biological systems. Health Phys 1991, 61, 15-28.
24. Brighton CT, Wang W, Seldes R, Zhang G, Pollack SR. Signal transduction in
electrically stimulated bone cells. J Bone Joint Surg Am 2001, 83A, 1514-1523.
25. Arnaud C. Weak forces. Chem Eng News 2007, 85, 12.
28. Bassett CAL. Beneficial effects of electromagnetic fields. J Cellular Biochem 1993, 51,
387-393.
29.Adey WR. Biological effects of electromagnetic fields. J Cellular Biochem 1993, 51, 410-
416.
29
30. Frey AH. Electromagnetic field interactions with biological systems. FASEB J 1993, 7,
272-281.
32. Uzdenslry AB. A cytologist’s view of resonance mechanism for biologic effects of ELF
33. Funk RHW, Monsees TK. Effects of electromagnetic fields on cell: physiological and
34. Meral I, Mert H, Mert N, Deger Y, Yoruk I, Yetkin A, Keskin S. Effects of 900 MHz
electromagnetic field emitted from cellular phone on brain oxidative stress and some
oxidative stress in duckweed Lemna minor L. Sci Total Environ 2007, 388, 78-89.
37. Yureli AI, Ozkan M, Kalkan T, Saybasili H, Tuncel H, Atukeren P, Gumustas K, Seker
S. GSM base station electromagnetic radiation and oxidative stress. Electromag Biol Med
38. Ozgumer F, Bardak Y, Comleckci S. Protective effects of melatonin and caffeic acid
phenylethyl ester against retinal oxidative stress in long-term use of mobile phone: a
30
39. Ozguner F, Altinbas A, Ozaydin M, Dogan A, Vural H, Kisioglu AN, Cesur G, Yildrim
agent caffeic acid phenethyl ester. Toxicol Indust Health 2005, 21, 223-230.
40. Koyu A, Ozguner F, Yilmaz HR, Uz E, Cesur G, Ozcelik N. The protective effect of
caffeic acid phenethyl ester (CAPE) on oxidative stress in rat liver exposed to the 900
electromagnetic radiation (RF-EMR) from GSM (0.9/1.8 GHz) mobile phones induces
43. Koh EK, Ryu B-K, Jeong D-Y, Bang I-S, nam MH, Chae K-S. A 60 MHz-sinusoidal
magnetic field induces apoptosis of prostate cancer cells through reactive oxygen species.
44. Zeni O, Pietro RD, d’Ambrosio G, Massa R, Capri M, Naarala J, Juutilaninen Scafi MR.
Formation of reactive oxygen species in L929 cells after exposure to 900 MHz radiation
45. Gudkova OY, Gudkov SV, Gapeev AB, Bruskov VI, Rubanik AV, Chemeris NK. Study
31
46. Lockwood DB, Wataha JC, Lewis JB, Tseng WY, Messer RLW, Hsu SD. Blue light
generates reactive oxygen species (ROS) differentially in tumor vs. normal epithelial
chemically induced reactive oxygen species production and DNA damage in human SH-
SY5Y neuroblastoma cells by 872 MHz radiofrequency radiation. Mut Res 2009, 662,
54-58.
cornea and lens of rats. Current Eye Res 2007, 32, 21-25.
microwave radiation from mobile phones in rat brain. J Radiat Res 2008, 49, 579-586.
activities in erythrocytes and heart, kidney, liver, and ovary tissues from rats:possible
52. Jagetia GC, Reddy TK. Modulation of radiation-induced alteration in the antioxidant
32
53. Lee K-S, Choi J-S, Hong S-Y, Son T-H, Yu K. Mobile phone electromagnetic radiation
54. Pratt PF, Bienengraeber M, Weihrauch D, kersten JR, Warltier DC. Myocardial
55. Iuliis GN, Newey RJ, King BV, Aitkin RJ. Mobile phone radiation induces reactive
oxygen species production and DNA damage in human spermatozoa on vitro. Plos One
2009, 4, e6446.
58. El-Swefy S, Soliman H, Hussein M. Calcium channel blockade alleviates brain injury
induced by long term exposure to an electromagnetic field. J Appl Biomed 2008, 6, 153-
163.
59. Luben RA. Membrane signal-transduction mechanisms and biological effects of low-
60. Patterson TE, Sakai Y, Grabiner MD, Ibiwoye M, Midura RJ, Zborowski M, Wolfman A.
Exposure of murine cells to pulsed electromagnetic fields rapidly activates the mTOR
33
61. Schnoke M, Midura RJ. Pulsed electromagnetic fields rapidly modulate intracellular
63. Beebe SJ, Fox PM, Rec LJ, Willis LK, Schoenbach KH. Nanosecond, high-intensity
pulsed electric fields induce apoptosis in human cells. FASEB J 2003, 17, 1493-1495.
65. Clejan S, Ide C, Walker C, Wolf E, Corb M, Beckman B. Electromagnetic field inducd
changes in lipid second messengers. J Lipid Mediat Cell Signal1996, 13, 301-324.
66. Pacini S, Vannelli GB, Ruggiero T, Sardi I, Pacini P, Gulisano M. Effect of 0.2 T static
cells exposed to low energy electromagnetic fields. J Biol Chem 1998, 273, 4305-4039.
dependent protein kinase A activity in human skin fibroblasts and rat osteoblasts by
34
extremely low-frequency electromagnetic fields. Radiat Environ Biophys 1999, 38, 195-
199.
69. Lindström E, Still M, Mattsson M-O, Mild KH, Luben RA. ELF magnetic fields initiate
70. Lindström E, Mild KH, Lundgren E. Analysis of the T cell activation signaling pathway
during ELF magnetic field exposure, p56lck and [Ca2+]i- measurements. Bioelectrochem
71. Markov MS, Pilla AA. Weak static magnetic field modulation of myosin
72. Liburdy RP Calcium signaling in lymphocytes and ELF fields. Evidence for an electric
field metric and a site of interaction involving the calcium ion channel. FEBS Lett 1992,
301, 53-59.
73. Walleczek J. Electromagnetic field effects on cells of the immune system: the role of
74. Roux D, Vian A, Girard S, Bonnet P, Paladian F, Davies E, Ledoigt G. High frequency
stimulus that affects transcription, translation, calcium and energy charge in tomato.
75. Yost MG, Liburdy RP. Time-varying static magnetic fields act in combination to alter
calcium signal transduction in the lymphocyte. FEBS Lett 1992, 296, 117-122.
35
76. Libury RP, Callahan DE, Harland J, Dunham E, Sloma TR, Yaswen P. Experimental
evidence for 60 Hz field operating through the signal transduction cascade. Effects on
calcium influx and c-MYC mRNA induction. FEBS Lett 1993, 334, 301-308.
77. Lyle DB, Fuchs TA, Casamento JP, Davis CC, Swicord ML. Intracellular calcium
kinase C and cell cycle in human cells. Mol Cellular Biochem 2002, 232, 133-141.
79. Malagoli D, Gobba F, Ottaviani E. Effects of 50-Hz magnetic fields on the signaling
80. Kovacic P. Cell signaling (mechanism and reproductive toxicity): redox chains, radicals,
electrons, relays, conduit, electrochemistry and other medical implications. Birth Defects
559-568.
molecular mechanism for cancer- and blood brain barrier-related effects. Differentiation
83. McDonald F. Electrical effects at the bone surface. Eur J Orthodontics 1993, 15, 175-183.
36
84. Aaron RK, Ciombor DM. Therapeutic effects of electromagnetic fields in the stimulation
85. Li JK-J, Lin JC-A, Liu H-C, Sun J-S, Ruaan R-C, Shih C, Chang WH-S. Comparison of
ultrasound and electromagnetic field effects on osteoblast growth. Ultrasound Med Biol
86. Lohmann CH, Schwartz, Liu Y, Li Z, Simon BJ, Sylvia VL, Dean DD, Bonewald LF,
Donahue HJ, Boyan BD. Pulsed electromagnetic fields affected phenotype and connexin
87. Simko M, Droste S, Kriehuber R, Weiss DG. Stimulation of phagocytosis and free
88. Chen G, Upham BL, Sun W, Chang CC, Rothwell EJ, Chen KM Yamasaki H, Trosko JE.
89. Ladokhin AS, White SH. Protein chemistry at membrane interfaces: non-additivity of
90. Aaron RK, Boyan BD, Ciombor DM, Schwartz Z, Simon BJ. Stimulation of growth
factor synthesis by electric and electromagnetic fields. Clin Orthopaed Relat Res 2004,
419, 30-37.
37
apoptosis and inactivation of the multi-chaperone complex in human epidermal cancer
93. Wei M, Guizzetti M, Yost M, Costa LG. Exposure to 60-Hz magnetic fields and
proliferation of human Astrocytoms cells in vitro. Toxicol Appl Pharmacol 2000, 162,
166-176.
fields increase cell survival by inhibiting apoptosis via modulation of Ca2+ influx.
95. Robison JG, Pendleton AR, Monson KO, Murray BK, O’Neill KL. Decreased DNA
repair rates and protection from heat induced apoptosis mediated by electromagnetic field
96. Dini L, Abbro L. Bioeffects of moderate-intensity static magnetic fields on cell cultures.
97. Goodman R, Blank M. Magnetic field stress induces expression of hsp70. Cell Stress
98. Gartzke J, Lange K. Cellular target of weak magnetic fields: ionic conduction along actin
99. Maccarrone M, Bladergroen MR, Rosato N, Finazzi Agro AF. Role of lipid peroxidation
417-425.
38
100. Krauss G. Biochemistry of Signal Transduction and Regulation. Wiley-VCH, Berlin,
101.Maeda K, Robinson AJ, Henbest KB, Dell EJ, Timmel CR. Protein surface interactions
probed by magnetic field effects on chemical reactions. J Am Chem Soc 2010, 132,
1466-1467.
102. Bókkon I, Dai J, Antal I. Picture representation during dreams: a redox molecular
103. Richards MA, Koren SA, Persinger MA. Circumcerebral application of weak complex
within the theta range: implications for state consciousness. Percept Mot Skills. 2002,
95, 671-686.
104. Lapitskaya N, Coleman MR, Nielsen JF, Gosseries O, Noordhout AM. Disorders of
Human ventral partial cortex plays a functional role on visuospatial attention and
Ovadia S, Stanziano M, Papa M, Laureys S, Malach R. Reaching across the abyss: recent
39
107. Martin JB, Ahles TA, Jeffery R. The role of private body consciousness and anxiety in
the report of somatic symptoms during magnetic resonance imaging. J Behav Ther Exp
108. Park SJ, Hur JW, Kwon KY, Rhee JJ, Lee JW, Lee HK. Time to recover consciousness
in patients with diffuse axonal injury: assessment with reference to magnetic resonance
110. Martin TE. Using functional magnetic resonance imaging to understand the mechanisms
111.Carrillo-Ruiz JD, Velasco F, Jiménez F, Castro G, Velasco AL, Hernández JA, Ceballos
112. Jiménez F, Velasco F,Carrillo-Ruiz JD, García L, Madrigal A, Velasco AL, Márquez I.
the globus pallidus internus in advanced Parkinson’s disease. Stereotact Funct Neurosurg
stimulation of the subthalamic nucleus in Parkinson’s disease: kinetic and kinematic gait
40
114. Temel Y, Wilbrink P, Duits A, Boon P, Tromp S, Ackermans L, van Kranen-
115. Mannu P, Rinaldi S, Fontani V, Castagna A, Margotti ML. Radio electrical treatment
vs. Es-Citalopram in the treatment of panic disorders associated with major depression
116. Shealy CN. Transcutaneous electrical nerve stimulation: the treatment of choice for pain
117. Fregni F, Liebetanz D, Monte-Silva KK, Oliveira MB, Santos AA, Nitsche MA,
with repetitive electrical stimulation on cortical spreading depression. Exp Neurol 2007,
204, 462-466.
118. Jin H, Kang KA. Application of novel metal nanoparticles as optical/thermal agents in
Experimental Medicine and Biology Maguire DJ, Bruley DF, Harrison DK, Eds,
119. Mornet S, Vasseur S, Grasset F, Duguet E. Magnetic nanoparticle design for medical
120. Jain PK, El-Sayed IH, El-Sayed MA. Au nanoparticles target cancer. Nanotoday 2007,
2, 18-29.
121. Ciombor DMK, Aaron RK. The role of electrical stimulation in bone repair. Foot Ankle
41
122.Chang K, Chang WH, Huang S, Huang S, Shih C. Pulsed electromagnetic fields
and macrophage colony stimulating factor. J Orthop Res 2005, 23, 1308-1314.
123. Dhawan SK, Conti SF, Towers J, Abidi NA, Vogt M. The effect of pulsed
124. Simmons JW, Moony V, Thacker I. Pseudarthrosis after lumbar spine fusion:
nonoperative salvage with pulsed electromagnetic fields. Am J Orthop 2004, 33, 27-30.
42