review article bioeffects of static magnetic fields:...

Hindawi Publishing CorporationBioMed Research InternationalVolume 2013 Article ID 602987 12 pageshttpdxdoiorg1011552013602987

Review ArticleBioeffects of Static Magnetic Fields Oxidative Stress GenotoxicEffects and Cancer Studies

Soumaya Ghodbane Aida Lahbib Mohsen Sakly and Hafedh Abdelmelek

Universite de Carthage Laboratoire de Physiologie Integree Faculte des Sciences de Bizerte 7021 Jarzouna Tunisia

Correspondence should be addressed to Soumaya Ghodbane ghodhbanesyahoofr

Received 24 April 2013 Revised 11 July 2013 Accepted 11 July 2013

Academic Editor Ali Khraibi

Copyright copy 2013 Soumaya Ghodbane et al This is an open access article distributed under the Creative Commons AttributionLicense which permits unrestricted use distribution and reproduction in any medium provided the original work is properlycited

The interaction of static magnetic fields (SMFs) with living organisms is a rapidly growing field of investigation The magneticfields (MFs) effect observed with radical pair recombination is one of the well-known mechanisms by which MFs interact withbiological systems Exposure to SMF can increase the activity concentration and life time of paramagnetic free radicals whichmight cause oxidative stress genetic mutation andor apoptosis Current evidence suggests that cell proliferation can be influencedby a treatment with both SMFs and anticancer drugs It has been recently found that SMFs can enhance the anticancer effect ofchemotherapeutic drugs this may provide a new strategy for cancer therapy This review focuses on our own data and other datafrom the literature of SMFs bioeffects Three main areas of investigation have been covered free radical generation and oxidativestress apoptosis and genotoxicity and cancer After an introduction on SMF classification and medical applications the basicphenomena to understand the bioeffects are described The scientific literature is summarized integrated and critically analyzedwith the help of authoritative reviews by recognized experts international safety guidelines are also cited

1 Introduction

Living organisms are continuously exposed to the naturalgeomagnetic field of around 20ndash70120583T that exists over thesurface of the Earth andwhich is implicated in the orientationand migration of certain animal species [1]

During evolution living organisms developed specificmechanisms for perception of natural electric and magneticfields These mechanisms require specific combinations ofphysical parameters of the applied field to be detected bybiological systems In order words the ldquowindowsrdquo are meansby which discrete MFs are detected by biological systemsDepending on the level of structural organization thesemechanisms of detection and response may be seen at differ-ent levels for example at membrane cellular or tissue levelsSometimes the ldquowindowsrdquo function via signal transductioncascade brain activity or the central nervous system [2]The sensitivity of the biological systems to weak MF hasbeen described elsewhere [3ndash5] mainly in respect to thedependence of bioeffects on the amplitude or the frequencyof applied fields

The frequency of exposure to MFs has increased withrapid advances in science and technology such as magneticresonance imaging (MRI) diagnosis nuclear magnetic reso-nance (NMR) spectroscopy and passenger transport systemsthat are based on magnetic levitation [6] Therefore it hasbecome necessary to systematically elucidate the influenceof MFs on the body In an attempt to explain the biologicaleffects of SMFs it is useful to classify them as weak (lt1mT)moderate (1mT to 1 T) strong (1ndash5 T) and ultrastrong (gt5 T)

SMFs are time-independent fields whose intensity couldbe spatially dependent There are four SMF parametersrelevant for the interaction with a biological system targettissue(s) magnet characteristics magnet support device anddosing regimen [7] SMFs are difficult to shield and canfreely penetrate biological tissues [8] However not onlythe field intensity but also the gradient of the field hasimportant role in biological effects of SMF [9 10] SMFcan interact directly with moving charges (ions proteinsetc) and magnetic materials found in tissues through severalphysical mechanisms [6]

2 BioMed Research International

Previous research showed that SMF influences biologicalsystem in a way that causes proinflammatory changes as wellas an increase in production of reactive oxygen species (ROS)[11 12] Throughout the past decades there have been severalexperimental results describing the effects of MFs on radicalpair recombination

As reviewed recently byUeno and Shigemitsu [13] severalbiophysical and biochemical effects can be expected whenbiological systems are simultaneously exposed to SMFs andother forms of energy such as light and radiation [14 15]

Although there is much speculation about this role theprimary mechanism is thought to be the result of oxidativestress that is free radical generation via Fenton reactionwhich is the iron-catalyzed oxidation of hydrogen peroxide(H2O2) [16ndash18]

Recent advance of biological science and technology canhelp us understand MF effects more clearly Studies on thebiological effects of MFs have resulted in significant develop-ments in themedical applications of SMF aswell as EMF afterthe development of high-strength superconducting magnetsThe mainstays of such medical applications are transcranialmagnetic stimulation (TMS) andMRIThese techniques havealso contributed much to the amazing progress made inunderstanding brain functions A guideline for exposure ofthe human body to SMFs set by the international commissionon nonionizing radiation protection (ICNIRP) [19] suggests2 T as the ceiling value for body parts except for arms andlegs in occupational exposure In the application of clinicalMRI the current exposure level is confirmed to be less than orequal to 2 T In SMFs at this strength it is not feasible to obtainresonance images except for hydrogen atoms There areseveral reports that strong SMF effects play significant rolesin endogenous and exogenous ROS generations Based onadvanced studies of SMF effects on oxidative stress reactionsthe potentially hazardous effect of SMF on living organisms isthat exposure to SMF can increase the activity concentrationand life time of paramagnetic free radicals whichmight causeoxidative stress genetic mutation andor apoptosis [20ndash23] In particular SMF exposure initiates an iron-mediatedprocess that increases free radical formation in brain cellsleading to the breaking of DNA strands and cell death

Genotoxic effects of exposure to static magnetic fieldshave been mostly examined in cell cultures [24] Few invivo studies of genotoxicity or possible effects on othercarcinogenic processes have been carried out Animal studiesare often used in the evaluation of suspected human car-cinogens [25] either screening for an increased incidence ofspontaneous tumors or of the incidence of tumors induced byknown carcinogens

The earlier literature has been summarized byWHO [26]Kowalczuk et al [27] and ICNIRP [28 29] Repacholi andGreenebaum [30] IARC [31] ICNIRP [32] McKinlay et al[33] andDini andAbbro [34] whilstmore recent studies havebeen reviewed by Okano [22] Phillips et al [35] and Uenoand Okano [36]

The focus of this review is on recent studies where pos-sible These studies are covered under three main sectionsfree radical generation and oxidative stress apoptosis andgenotoxicity and cancer

The objective of this review is to describe and shed lighton some of the most recent information on the biologicaleffects and medical applications of magnetic fields A dis-cussion of possible implications of these effects on biologicalsystems is also provided

2 Oxidative Stress

Biological free radicals are most commonly oxygen ornitrogen based with an unpaired electron leading to theterms ROS such as superoxide anion (O2minus) hydroxyl radical(OH∙) and singlet oxygen (

1O2) or ldquoreactive nitrogen species

(RNS)rdquo such as nitric oxide (NO) [37]TheROS andRNSplaysignificant roles in immunological defense [38] intracellularsignaling [39] and intercellular communication [40] It isassumed that SMF could change the lifetime of radical pairsyields of cage products and escape products If an SMF affectscells through the radical pair mechanism an SMF influencesthe spin of electrons in free radicals which may lead tochanges in chemical reaction kinetics and possibly alteringcellular function [41]

21 Moderate-Intensity Static Magnetic Fields and OxidativeStress There are several reports showing that moderate SMFcould influence the ROS modulation (generationreduction)from enzymatic reactions in cell-free solutions The SMFeffects also play significant roles in the endogenous andexogenous ROS modulation in biological systems in vitroand in vivo

Amara et al [42] investigated the effect of SMF expo-sure on testicular function and antioxidant status in ratsExposure to SMF (128mT 1 hday for 30 days) has noeffect on epididymal sperm count spermatozoa motility andgenital organ weight In contrast SMF induces an increaseof malondialdehyde (MDA) in the testis In the gonadSMF decreases the catalase (CAT) glutathione peroxidase(GPx) and mitochondrial Mn-superoxide dismutase (Mn-SOD) activities However cytosolic CuZn-SOD activity isunaffected

The latter group also investigated the effects of SMF(128mT 1 hday during 30 consecutive days) exposure on theantioxidative enzymes activity and MDA concentration inmale rat brain [43] The exposure of rats to SMF decreasedthe GPx CuZn-SOD and CAT activities in frontal cortexThe same treatment decreased the CuZn-SOD and Mn-SOD activities in hippocampus However the glutathionelevels remained unchanged in both brain structures In thehippocampus SMF-exposure increasedMDA concentrationThese results indicated that exposure to SMF induced oxida-tive stress in rat hippocampus and frontal cortex

SMF exposure alters antioxidant enzyme activity and thelabile zinc fraction in THP1 cells (monocyte line) [44] Cellculture flasks were exposed to SMF (250mT) during 1 h 2 hand 3 h Cell viability was slightly lower in SMF-exposedgroups compared to a sham-exposed group However SMFexposure failed to alter MDA GPx CAT and SOD levelseven by 3 h of exposition Cells stained with zinc-specificfluorescent probes zinpyr-1 showed a decrease of labile zinc

BioMed Research International 3

fraction in all groups exposed to SMF SMF exposure (250mTduring 3 h) did not cause oxidative stress in THP1 cells butaltered the intracellular labile zinc fraction

Chater et al [45] evaluated the effects of exposure toSMF on some parameters indicative of oxidative stress inpregnant rat Exposure to SMF (128mT 1 hday from day6 to day 19 of pregnancy) failed to alter plasma MDA andGPx activity Moreover the same treatment did not alter liverconcentration ofMDA and kidney activities of GPx CAT andSOD By contrast SMF induced an increase of liver GSHcontent Similar results were reported byGhodbane et al [46]who show that liver GSH concentrations were significantlyhigher in SMF exposed rats than in the controls indicatingan adaptive mechanism to electromagnetic pollution GSHlevels can be increased due to an adaptivemechanism to slightoxidative stress through an increase in its synthesis Howevera severe oxidative stress may decrease GSH levels due to theloss of adaptive mechanisms and the oxidation of GSH toGSSG

Exposure to SMF (128mT 1 hday for 5 days) induces adecrease of selenium levels in kidney muscle and brain witha decrease ofGPx activities in kidney andmuscle By contrastSMF exposure increased total GSH levels and total SODactivities in liver while glutathione reductase (GR) activity isunaffected Selenium supplementation (Na

2SeO3 02mgL

in drinking water for 4 weeks) in SMF-exposed rats restoredselenium levels in kidney muscle and brain and elevated theactivities of GPx in kidney and muscle to those of controlgroup In the liver selenium supplementation failed to bringdown the elevated levels of total GSH and SOD activities[46]Thus subacute exposure to SMF altered the antioxidantresponse by decreasing tissues selenium contents whileselenium supplementation ameliorates antioxidant capacityin rat exposed to SMF Regarding the fate of seleniumadministration in SMF-exposed rats it may be assumed thatthis element minimizes the oxidative stress induced by SMF

Previous data implicated the SMF in free radical pro-duction like superoxide anions in different cells and organs[22 47 48] However Ghodbane et al [49] showed thatSMF exposure failed to alter plasma TBARs and total thiolgroups indicating an adaptive mechanism to slight oxidativestress caused by electromagnetic field as previously shownby Chater et al [45] By contrast Amara et al [50] showedan increase in MDA level in liver and kidney indicatingoxidative stress under SMF (128mT 1 hday during 30 con-secutive days) This discrepancy may be explained by theintensity and the duration of the exposure The cellular andmolecular modifications induced when SMFs interact withbiological materials are however dependent on the durationof exposure intensity tissue penetration and the type of cells[51]

Moreover Ghodbane et al [49] evaluated the effect ofselenium (Se) supplementation in SMF-exposed rats Pre-treatment with Se (Na

2SeO3 02mgL for 30 consecutive

days per os) prevented plasma 120572-tocopherol and retinoldecrease induced by SMF exposure

Amara et al [50] examined the effect of zinc supplemen-tation on the antioxidant enzymatic system lipid peroxida-tion and DNA oxidation in SMF-exposed rats The exposure

of rats to SMF (128mT 1 hday during 30 consecutive days)decreased the activities of GPx CAT and SOD activitiesand increased MDA concentration in liver and kidneys Zincsupplementation (ZnCl

2 40mgL per os) in SMF-exposed

rats restored the activities of GPx CAT and SOD in liverto those of control group However only CAT activity wasrestored in kidney Moreover zinc administration was able tobring down the elevated levels of MDA in the liver but notin kidneys The authors suggested that zinc supplementationminimizes oxidative damage induced by SMF in rat tissues

The mechanism by which SMF induced oxidative stressin rat tissues is not well understood A change in radical pairrecombination rates is one of the few mechanisms by whichan SMF can interact with biological systems such as a cell-freesystem The SMF increases the concentration andor lifetimeof free radicals that escape from the radical pair so that thecritical radical concentration needed to initiate membranedamage and cause cell lysis is reached sooner [22]

Exposure to SMF (128mT 1 hday during 5 consecu-tive days) induced sympathetic neurons system hyperac-tivity associated with hypoxia-like status [52] and elevatedplasma corticosterone and metallothionein concentrationsand enhanced apoptosis [53 54] Hashish et al [8] indicatethat there is a relation between the exposure to SMF and theoxidative stress through distressing redox balance leading tophysiological disturbances SMF exposure induced probablythe disruption of mineral divalent element homeostasis con-tributing to their deficiency in tissues [43 44 46 50] Agayet al [55] have demonstrated that alteration of antioxidanttrace elements (Zn Se and Cu) disrupts the activities ofantioxidant enzymes Duda et al [56] reported a changein liver and kidneys concentration of copper manganesecobalt and iron in rats exposed to static and low-frequencymagnetic fields SMF probably induces a conformationalchange of antioxidant enzymes that leads to loss of theircatalytic activity [56]

A few studies concerning the supplemental antioxidantsvitamins C and E have focused on the preventive and curativeproperties in damage induced by SMF exposure [57] Jajteet al [58] reported the effect of melatonin and vitamin Eon the level of lipid peroxidation in rat blood lymphocytesexposed to iron ions andor SMF When cells were treatedwith melatonin or vitamin E and then exposed to iron ionsand SMF the level of lipid peroxidation was significantlyreduced

Sullivan et al [59] reported that SMF (230ndash250mT)exposure stimulates ROSproduction in human fetal lung cells(WI-38) during the first 18 h period when cells are attachingto the culture vessel These results support the hypothesisthat increased ROS formation may account for SMF effectson cell attachment However SMF decreases growth in cellwhen the increase in ROS was abated suggesting that othermechanisms account for SMF effects on cell growth

Kabuto et al [60] showed that an SMF (5ndash300mT for40min) had no effect on the accumulation of TBARS inmouse brain homogenates induced by FeCl

3 In contrast

when the homogenates were incubated with FeCl3in an

SMF (2ndash4mT) the accumulation of TBARS was decreasedThe accumulation of TBARS in phosphatidylcholine solution


incubatedwith FeCl3andH

2O2was also inhibited by the SMF

exposure These results suggest that the SMF could have aninhibitory effect on Fe2+-induced lipid peroxidation and theeffectiveness of this SMF suppression on Fe2+-induced ROSgeneration is restricted to a ldquowindowrdquo of field intensity of 2 to4mT

Currently environmental and industrial pollution causesmultiple stress conditions the combined exposure to mag-netic field and other toxic agents is recognized as an impor-tant research area with a view to better protecting humanhealth against their probable unfavorable effects Amaraet al [61] investigated the effect of coexposure to SMF andcadmium (Cd) on the antioxidant enzymes activity andMDA concentration in rat skeletal and cardiac musclesThe exposure of rats to SMF (128mT 1 hday during 30consecutive days) decreased the activities of GPx and CuZn-SOD in heart muscle Exposure to SMF increased the MDAconcentration in rat cardiac muscle The combined effectof SMF and Cd (CdCl

2 40mgL per os) disrupted more

the antioxidant enzymes activity in rat skeletal and cardiacmuscles

The combined effect of SMF (128mT 1 hourday for 30consecutive days) and CdCl

2(40mgL per os) decreased

SOD activity and glutathione level and increased MDAconcentration in frontal cortex as comparedwithCd-exposedrats [62]

In pregnant rats coexposed to cadmium (CdCl2

30mgKg body weight) and SMF (128mT1 hday) for 13consecutive days as from the 6th to 19th day of gestationno effects on activities of antioxidant were observed in bothtissues compared to cadmium-treated group [63] Howeverthe association between SMF and Cd decreased plasmaMDA concentration suggesting that a homeostatic defensemechanism was activated when SMF was associated to Cd inpregnant rats

22 Strong and Ultrastrong Static Magnetic Fields and Oxida-tive Stress Although strong SMF is supposed to have thepotential to affect biological systems the effects have not beenevaluated sufficiently

Sirmatel et al [64] investigated the effects of a high-strength magnetic field produced by an MRI apparatus onoxidative stress The effects of SMF (150 T) on the totalantioxidant capacity (TAC) total oxidant status (TOS) andoxidative stress index (OSI) in male subjects were inves-tigated In this study 33 male volunteers were exposed toSMF for a short time and the TAC TOS and OSI ofeach subject were determined using the methods of ErelMagnetic field exposure was provided using a magneticresonance apparatus radiofrequency was not applied TACshowed a significant increase in postexposures compared topreexposures to the magnetic field (119875 lt 005) OSI and TOSshowed a significant decrease in postexposures compared topreexposures to SMF (for each of two 119875 lt 001) The 150 TSMFused in theMRI apparatus did not yield a negative effecton the contrary it produced the positive effect of decreasingoxidative stress in men following short-term exposure

The Nakagawa research group [65 66] measured andevaluated a ROS scavenger metallothionein (MT) a ROS

product and lipid peroxidation in the liver kidneys heartlung and brain of 8-week-old male BALBc mice in vivo Themice were exposed to an SMF of 30 and 470 T for 1ndash48 h A470 T SMF exposure for 6ndash48 h increased bothMT and lipidperoxidation levels in the liver alone A 30 T SMF exposurefor 1ndash48 h did not induce any changes in both MT and lipidperoxidation levels in all the tissues A single subcutaneousinjection of CCl

4(05mLkg) increased both MT and lipid

peroxidation levels in the liver and the combination ofCCl4administration and a 470 T SMF for 24 h potentiated

both MT and lipid peroxidation levels The increase inactivities of both glutamic-oxaloacetic transaminase (GOT)and glutamic-pyruvic transaminase (GPT) caused by CCl

4

administration was also enhanced by the SMF exposure It isconcluded that exposure to a high SMF induces the increaseof both MT and lipid peroxidation levels in the liver of miceand enhances the hepatotoxicity caused by CCl

4injection

3 Genotoxicity DNA Damage and Apoptosis

Health and environmental concerns have been raised becausethe SMF effects on oxidative stress leading to genetic muta-tion and apoptosisnecrosis have been found It seems to takeplace from free radical generation

Several experiments have been shown and they discussedhow SMF can influence the immune function or oxidativeDNA damage via the ROS formation process

One possibility is that DNA is damaged by free radicalsthat are formed inside cells Free radicals affect cells by dam-agingmacromolecules such asDNA protein andmembranelipids Several reports have indicated that SMF enhances freeradical activity in cells [67ndash71] particularly via the Fentonreaction [70] The Fenton reaction is a process catalyzed byiron in which hydrogen peroxide a product of oxidativerespiration in the mitochondria is converted into hydroxylfree radicals which are very potent and cytotoxic molecules

31 Genotoxic Effects of Moderate-Intensity Static MagneticFields Amara et al [44] investigated the effect of SMFexposure in DNA damage in THP1 cells (monocyte line)Cell culture flasks were exposed to SMF (250mT) during1 h 2 h and 3 h The results showed that cell viability wasslightly lower in SMF-exposed groups compared to a sham-exposed groupDNAanalysis by single cell gel electrophoresis(comet assay) revealed that SMF exposure did not exert anyDNA damage by 1 and 2 h However it induced a low levelof DNA single strand breaks in cells after 3 h of expositionTo further explore the oxidative DNA damage cellular DNAwas isolated hydrolyzed and analyzed by HPLC-EC Thelevel of 8-oxo-78-dihydro-21015840-deoxyguanosine (8-oxodGuo)remained unchanged compared to the sham-exposed group(+65 119875 gt 005) The results showed that SMF exposure(250mT during 3 h) did not cause oxidative stress and DNAdamage in THP1 cells

Exposure of rats to SMF (128mT 1 hday during 30consecutive days) increased metallothioneins level in frontalcortex while the 8-oxodGuo concentration remained unaf-fected indicating the absence of DNA oxidation Metalloth-ionein induction protected probably DNA against oxidative


damage [43] The same treatment elevated the 8-oxodGuoin kidneys but not in liver Zinc supplementation (ZnCl

2

40mgL per os) attenuated DNA oxidation induced by SMFin kidneys to the control level [50]

Simultaneous exposure of rat lymphocytes to a 7mTSMF and ferrous chloride (FeCl

2) caused an increase in the

number of cells withDNAdamage [72 73] No significant dif-ferences were observed between unexposed lymphocytes andlymphocytes exposed to a 7mT SMF or FeCl

2(10mgmL)

However when lymphocytes were exposed to a 7mT staticmagnetic field and simultaneously treated with FeCl

2 there

was a significant increase in the percentage of apoptotic andnecrotic cells accompanied by significant alterations in cellviability

However an increasing number of evidence indicatesthat SMFs are capable of altering apoptosis mainly throughmodulation of Ca2+ influx Tenuzzo et al [74] observedthat exposure to a 6-mT SMF affects the apoptotic rate inisolated human lymphocytes the expression and distributionof pro- and antiapoptotic genes and the concentration ofintracellular Ca2+ They also suggest that modulation of theapoptotic rate is not a consequence of the direct physicalinteraction between the field and the apoptotic inducers butthe final result of multiple perturbations of Ca2+-regulatedactivity and gene-related transcription factors andmembranecomponents which collectively affect the apoptotic response

SMFs above 600mT were found to decrease the extent ofcell death by apoptosis induced by several agents in differenthuman cell systems of U937 and CEM cells in an intensity-dependent fashion reaching a plateau at 6mT [75] Theprotective effect was found to bemediated by the ability of thefields to enhance Ca2+ influx from the extracellular mediumaccordingly it was limited to those cell systems where Ca2+influx was shown to have an antiapoptotic effect In additionto the SMF-enhancing effect on [Ca2+]i as a mechanism ofthe rescue of damaged cells it was recently proposed thatSMF-produced redox alterations may be part of the signalingpathway leading to apoptosis antagonism [76]

Flipo et al [77] examined the in vitro effects of SMFson the cellular immune parameters of the C57BI6 murinemacrophages spleen lymphocytes and thymic cellsThe cellswere exposed in vitro for 24 h at 37∘C 5 CO

2 to 25ndash

150mT SMF Exposure to the SMF resulted in the decreasedphagocytic uptake of fluorescent latex microspheres whichwas accompanied by an increased intracellular Ca2+ levelin macrophages Exposure to SMF decreased mitogenicresponses in lymphocytes as determined by incorporationof [3H] thymidine into the cells This was associated withthe increased Ca2+ influx in concanavalin A-stimulated lym-phocytes Furthermore exposure to SMF producedmarkedlyincreased apoptosis of thymic cells as determined by flowcytometry Overall in vitro exposure of immunocompetentcells to 25ndash150mT SMF altered several functional parametersof C57BI6 murine macrophages thymocytes and spleenlymphocytes [77]

Apoptosis induced by magnetic field in female rats wasinvestigated by using the Tdt mediated dUTP nick-endlabeling (TUNEL) assay in thymus liver and kidneys [54]

Following subacute exposure to SMF morphological exami-nations revealed numerous apoptotic cells in thymus charac-terized by nuclear chromatin condensation and fragmenta-tion The density of the apoptotic cells was significant incortical zone than in the medullar zone By contrast nolabeling was found in liver and kidneys following SMF-exposure Thus it may be concluded that SMF inducedapoptosis in thymic cell death but not in the liver and kidneysAlthough the mechanisms by which SMF initiates apoptosisin thymocytes are presently not known and reactive oxygenspecies are likely to play a role

Ishisaka et al [78] investigated the effects of an SMF(25mT for 1 h) on the apoptosis of human leukemic cell line(HL-60) induced by exogenous H

2O2 The H

2O2induced a

rapid DNA fragmentation and a slow decrease in viability ofHL-60 cells However the SMF itself (6mT for 18 h) did notexert any effect on the H

2O2-induced DNA fragmentation or

viabilityHL-60 cells were exposed to SMF of 6mTwith or without

DNA topoisomerase I inhibitor camptothecin for 5 h SMFalone did not produce any apoptogenic or neurogenic effectin HL-60 cells [79] SMFs alone or in combination with cam-ptothecin did not affect overall cell viability but they accel-erated the rate of cell transition from apoptosis to secondarynecrosis after induction of apoptosis by camptothecin

In addition Teodori et al [80 81] reported that a uniformSMF (6mT for 18 h 8 and 30mT for 3 h) did not affectviability of human glioblastoma cells However a uniformSMF of 300mT for 3 h increased apoptosis The interferenceof the SMF (6mT for 18 h) with physical (heat shock) orchemical (etoposide VP16) induced apoptosis may be relatedto oxidative stress

Potenza et al [82] described the effects of SMF oncell growth and DNA integrity of human umbilical veinendothelial cells (HUVECs) The authors investigated thata 4 h exposure of HUVECs to SMFs of moderate intensity(300mT) induced a transient DNA damage both at the nu-clear and mitochondrial levels This response was par-alleledby increased mitochondrial DNA content and mitochondrialactivity and by a higher expression of some genes related tomitochondrial biogenesis 24 h after SMF exposure

Hao et al [83] investigated whether SMFs (88mT for12 h) can enhance the killing effect of adriamycin (ADM)in human leukemia cells (K562) The authors showed thatSMF exposure enhanced the cytotoxicity potency of ADMonK562 cells and suggested that the decrease in P-glycoproteinexpression may be one reason underlying this effect

Sarvestani et al [84] evaluated the influence of an SMF(15mT for 5 h) on the progression of cell cycle in rat BMSCsThe cells were divided into two groups One group wasexposed to SMF alone whereas the other group was exposedto X-rays before SMF exposure The population of cells didnot show any significant difference in the first group butthe second group exposed to acute radiation before SMFexposure showed a significant increase in the number of cellsin the G2M phase The SMF intensified the effects of X-rayexposure whereas SMF alone did not have any detectableinfluence on cell cycle


32 Genotoxic Effects of Strong andUltrastrong StaticMagneticFields It is generally accepted that static fields below 1 T arenot genotoxic [32 33 85] However a recent study by Suzukiet al [86] reported a significant time- and dose-dependentincrease in micronucleus frequency in mice exposed to staticmagnetic fields of 2 3 or 47 T for 24 48 or 72 h usinga standard micronucleus assay Bone marrow smears weretaken immediately after exposure and the frequency ofmicronucleated polychromatic (immature) erythrocytes wasscored Micronucleus frequency was significantly increasedfollowing exposure to 47 T for all three time periods and to3 T after exposure for 48 or 72 h whereas exposure to 2 Thad no significant effectThe authors suggest that exposure tohigher fields may have induced a stress reaction or directlyaffected chromosome structure or separation during celldivision

The clinical and preclinical uses of high-field intensity(HF 3 T and above) magnetic resonance imaging (MRI)scanners have significantly increased in the past few yearsHowever potential health risks are implied in the MRI andespecially HF MRI environment due to high-static magneticfields fast gradient magnetic fields and strong radiofre-quency electromagnetic fields The genotoxic potential of3 T clinical MRI scans in cultured human lymphocytes invitro was investigated by analyzing chromosome aberrations(CA) micronuclei (MN) and single-cell gel electrophoresis[87] Human lymphocytes were exposed to electromagneticfields generated during MRI scanning (clinical routine brainexamination protocols three-channel head coil) for 22 4567 and 89min A significant increase in the frequency ofsingle-strand DNA breaks following exposure to a 3 T MRIwas observed In addition the frequency of both CAs andMN in exposed cells increased in a time-dependent mannerThe frequencies of MN in lymphocytes exposed to complexelectromagnetic fields for 0 22 45 67 and 89min were967 1167 1467 1800 and 2033 per 1000 cells respectivelySimilarly the frequencies of CAs in lymphocytes exposed for0 45 67 and 89min were 133 233 367 and 467 per 200cells respectively These results suggest that exposure to 3 TMRI induces genotoxic effects in human lymphocytes

Schreiber et al [88] reported no mutagenic and comuta-genic effects of magnetic fields used for MRI

Schwenzer et al [89] evaluated the effects of the staticmagnetic field and typical imaging sequences of a high-field magnetic resonance scanner (3 T) on the induction ofdouble strand breaks (DSBs) in twodifferent human cell linesHuman promyelocytic leukemia cells (HL-60) and humanacute myeloid leukemia cells (KG-1a) were exposed to theSMF alone and to turbo spin-echo (TSE) and gradient-echo (GE) sequences Flow cytometry was used to quan-tify gammaH2AX expression of antibody-stained cells as amarker for deoxyribonucleic acid DSBs one hour and 24hours after magnetic field exposure X-ray-treated cells wereused as positive control Neither exposure to the SMF alonenor to the applied imaging sequences showed significantdifferences in gammaH2AX expression between exposed andsham-exposed cells X-ray-treated cells as positive controlshowed a significant increase in gammaH2AX expression

SMF alone and MRI sequences at 3 T have no effect on theinduction of DSBs in HL-60 and KG-1a cells

The effects of SMF (470 T) on the frequency of micronu-cleated cells in CHLIU cells induced by mitomycin C(MMC) were studied in vitro [90] The cells were simulta-neously exposed to SMF and MMC for 6 h and then thecells were cultured in normal condition for the micronucleusexpression up to 66 h Exposure to SMF for 6 h significantlydecreased the frequency of MMC-induced micronucleatedcell expression after culture periods of 18 42 54 and 66 hThese results suggested that SMF (470 T) might have exertedan influence on the DNA damage stage produced by MMCrather than on the formation of micronuclei during the stagefollowing MMC-induced DNA damage

Kimura et al [91] examined the effect of 3 or 5 T SMFon gene expression in the experimental model metazoanCaenorhabditis elegans In addition transient induction ofhps12 family genes was observed after SMF exposure Thesmall-hps gene hps16 was also induced but to a muchlesser extent and the lacZ-stained population of hps16-1lacZtransgenic worms did not significantly increase after SMFexposure with or without a second stressor mild heat shockSeveral genes encoding apoptotic cell death activators andsecreted surface proteins were upregulated after ionizingradiation (IR) but they were not induced by SMF The RT-PCR analyses for 12 of these genes confirmed the expres-sion differences between worms exposed to SMF and thoseexposed to IR In contrast to IR exposure to high SMFsdid not induce DNA double-strand breaks or germ linecell apoptosis during meiosis These results suggest that theresponse of C elegans to high SMFs is unique and capable ofadjustment during long exposure and that this treatmentmaybe less hazardous than other invasive treatments and drugs

Koana et al [92] examined the genotoxic effects of a5 T SMF for 24 h in a DNA-repair defective mutant of Dmelanogaster using the somatic mutation and recombinationtest (SMART) [93] because this test was useful to detect themutagenic activity of SMF and EMF They reported that theSMF exposure increased the frequency of mutation inmei-41heterozygotes and that the increase was suppressed to controllevels by supplementation with vitamin E which is a lipid-soluble antioxidant and a nonspecific radical scavenger

An Escherichia coli (E coli) mutation assay was used toassess the mutagenic effects of strong static magnetic fields[21] Various mutant strains of E coli were exposed up to 9 Tfor 24 h and the frequencies of rifampicin-resistant muta-tions were then determined The expression of the soxSlacZfusion gene was assessed by measuring b-galactosidase activ-ity The results for survival or mutation obtained with thewild-type E coli strain GC4468 and its derivatives defectivein DNA repair enzymes or redox-regulating enzymes showedno effect of exposure On the other hand the mutationfrequency was significantly increased by exposure to SMF of9 T in soxR and sodAsodB mutants which are defective indefense mechanisms against oxidative stress

Ikehata et al [94] examined possible mutagenic andcomutagenic effects of strong static magnetic fields usingthe bacterial mutagenicity test No mutagenic effect of SMFsup to 5 T was detected using four strains of Salmonella


typhimurium and E coli WP2 uvrA The mutation ratein the exposed group was significantly higher than inthe nonexposed group when cells were treated with N-ethyl-N0-nitro-N-nitrosoguanidine N-methyl-N0-nitro-N-nitrosoguanidine ethylmethanesulfonate 4-nitroquinoline-N-oxide 2-amino-3-methyl-3H-imidazo[45-f]quinolone or2-(2-furyl)- 3-(5-nitro-2-furyl) acrylamide

Long-term exposure to a 10 T SMF for up to 4 days didnot affect cell growth rate or cell cycle distribution in Chinesehamster ovary CHO-K1 cells [95] Exposure to SMF alonedid not affect micronucleus formation In X-ray irradiatedcells exposure to a 1 T SMF also did not affect micronucleusformation but exposure to a 10 T SMF resulted in a significantincrease in micronucleus formation induced after a 4Gyexposure One of the mechanisms of this effect is attributableto the 10 T SMF-induced oxidative DNA damage

4 Cancer Studies

Many researchers have observed the effects of SMFs on tumorcells particularly the inhibiting effects They have used SMFas an entry point for investigating biological effects In orderto reduce the toxicity and resistance of single anticancerdrugs a variety of unified treatments were required Thesynergy of magnetic fields and anticancer drugs was one ofthe methods that provides a new strategy for the effectivetreatment of cancer

41 Moderate-Intensity Static Magnetic Fields and CancerGray et al [71] evaluated the effects of non-uniform 110mTSMF for four 4 h periods with 8ndash12 h between each exposureand doxorubicin (10mgkg ip) on female B6C3F1 micewith transplanted mammary adenocarcinoma Their resultsrevealed that the groups exposed to SMF combined withdoxorubicin achieved significantly greater tumor regressionthan the group treatedwith adriamycin (ADM) alone In an invivo experimentmice bearingmurine Lewis lung carcinomas(LLCs) were treated with 3mT SMF for 35minday andcisplatin (3mgkg ip) [96] The survival time of micetreated with cisplatin and SMF was significantly longer thanthat of mice treated only with cisplatin or SMF exposureThese results show that SMF can inhibit the proliferation ofcancer cells and the killing effects of SMF combined withantineoplastic drugs on cancer cells are greater than those ofSMFs or anticancer drugs aloneThese observations suggest apotential strategy for chemotherapy that is the combinationtherapy of SMFs and chemotherapeutic drugs Howeverso far it remains unclear which mechanism underlies thekilling effects of SMFs combined with chemotherapy drugson cancer cells

Sun et al [97] evaluated the ability of 88mT SMFs toenhance the in vitro action of a chemotherapeutic agentpaclitaxel against K562 human leukemia cells The authorsanalyzed the cell proliferation cell cycle distribution DNAdamage and alteration of cell surface and cell organelleultrastructure after K562 cells were exposed to paclitaxelin the presence or absence of SMF the results showedthat in the presence of SMF the efficient concentration of

paclitaxel on K562 cells was decreased from 50 to 10 ngmLCell cycle analysis indicated that K562 cells treated withSMF plus paclitaxel were arrested at the G2 phase whichwas mainly induced by paclitaxel Through comet assay theauthors found that the cell cycle arrest effect of paclitaxelwith or without SMF on K562 cells was correlated with DNAdamage The results of atomic force microscopy and trans-mission electron microscopy observation showed that thecell ultrastructure was altered in the group treated with thecombination of SMF and paclitaxel holes and protuberanceswere observed and vacuoles in cytoplasm were augmentedThe authors indicated that the potency of the combination ofSMF and paclitaxel was greater than that of SMF or paclitaxelalone on K562 cells and these effects were correlated withDNA damage induced by SMF and paclitaxel Thereforethe alteration of cell membrane permeability may be oneimportant mechanism underlying the effects of SMF andpaclitaxel on K562 cells

Strieth et al [98] analyzed the effects of SMF (le587mT)on tumor microcirculation In vivo fluorescence microscopywas performed in A-Mel-3 tumors growing in dorsal skinfoldchamber preparations of hamsters Short time exposureto SMF (ge150mT) resulted in a significant reduction ofcapillary red blood cells velocities (vRBC) and segmentalblood flow in tumor microvessels At the maximum strengthof 587mT a reversible reduction of vRBC (40) and offunctional vessel densities (FVD) (15) was observed Pro-longation of the exposure time (1 minute to 3 h) resulted inreductions Microvessel diameters and leukocyte-endothelialcell interactions remained unaffected by SMF exposuresHowever in contrast to tumor-free striated muscle controlsexposure at the maximum flux density of 587mT induced asignificant increase in platelet-endothelial cell adherence ina time-dependent manner that was reversible after reducingthe strength of the SMF The authors assumed that thesereversible changes may have implications for functionalmeasurements of tumor microcirculation by MRI and newtherapeutic strategies using strong SMFs The same researchgroup further evaluated the effects of an SMF (586mT for 3 h)on tumor angiogenesis and growth [99] Analysis of micro-circulatory parameters revealed a significant reduction ofFVD vessel diameters and RBC velocity in tumors after SMFexposure compared with the control tumors These changesreflect retarded vessel maturation by antiangiogenesis Theincreased edema after SMF-exposure indicated an increasedtumormicrovessel leakiness possibly enhancing drug uptakeThe authors concluded that SMF therapy appears to be apromising new anticancer strategy as an inhibitor of tumorgrowth and angiogenesis and as a potential sensitizer tochemotherapy

Chen et al [100] investigated whether 88mT SMFs canenhance the killing potency of cisplatin (DDP) on humanleukemic cells (K562) The results show that SMFs enhancedthe anticancer effect of DDP on K562 cells The mechanismcorrelated with the DNA damage model This study alsoshows the potentiality of SMFs as an adjunctive treatmentmethod for chemotherapy

Hao et al [83] investigated whether a moderate-intensitySMF can enhance the killing effect of ADM on K562 cells


and explore the effects of SMF combined with ADM onK562 cells The authors analyzed the metabolic activity ofcells cell cycle distribution DNA damage change in cellultrastructure and P-glycoprotein (P-gp) expression afterK562 cells were exposed continuously to a uniform 88mTSMF for 12 h with or without ADM Their results showedthat the SMF combined with ADM (25 ngmL) significantlyinhibited the metabolic activity of K562 cells while neitherADM nor the SMF alone affected the metabolic activity ofthese cells Cell ultrastructure was altered in the SMF+ADMgroup For example cell membrane was depressed someprotuberances were observable and vacuoles in the cyto-plasm became larger Cells were arrested at the G2M phaseand DNA damage increased after cells were treated withthe SMF+ADM ADM also induced the P-gp expression Incontrast in the SMF group and SMF+ADM group the P-gpexpression was decreased compared with the ADM groupTaken together these results showed that the 88mT SMFenhanced the cytotoxicity potency ofADMonK562 cells andthe decrease in P-gp expressionmay be one reasonunderlyingthis effect

Cells were treated with four anticancer drugs followed bytreatment with a combination of drugs and SMF [101] Indi-vidual cells were examined using atomic force microscopy(AFM)Thedrugswere taxol (alkaloid) doxorubicin (anthra-cycline) cisplatin (platinum compound) and cyclophos-phamide (alkylating agent) Holes were observed in cellsexposed to SMF but not in control groups The number sizeand shape of the holes were dependent on the drug typeSMF parameters and the duration of exposure The resultssuggest that the application of a SMF could alter membranepermeability increasing the flow of the anticancer drugsThismay be one of the reasons why SMF can strength then theeffect of anticancer drugs Observations were also made ofthe effect of using different anticancer drugs For examplethe effect of SMF combined with taxol or cyclophosphamideon the cells was additive while the effect of SMF combinedwith cisplatin or doxorubicin was synergistic The target sitesof cisplatin and doxorubicin are nucleic acids continousresearch is required into this important area to ascertain theeffect of SMF on nucleic acids

42 Strong and Ultrastrong Static Magnetic Fields and CancerRecently some studies have suggested that SMFs have thepotential as an adjunctive treatment method for chemother-apy since SMFs influence cell growth proliferation andstructure of cancer cells [98 99 102ndash107] In particularthe killing effect of antineoplastic drugs on cancer cellsis enhanced with a combined treatment of SMFs andchemotherapeutic drugs indicating that SMFs act synergi-cally with the pharmacological treatment [71 96 108] Forexample 64 h exposure to a 7 T uniform SMF produced areduction in viable cell number in HTB 63 (melanoma) HTB77 IP3 (ovarian carcinoma) and CCL 86 (lymphoma Rajicells) cell lines [102]

Ghibelli et al [109] examined whether exposure to theSMF of NMR (1 T) generated by anNMR apparatus can affectapoptosis induced on reporter tumor cells of hematopoi-etic origin The impressive result was the strong increase

(by 18ndash25-fold) of damage-induced apoptosis by NMRThispotentiation is due to cytosolic Ca2+ overload to NMR-promoted Ca2+ influx since it is prevented by intracellular(BAPTA-AM) and extracellular (EGTA) Ca2+ chelation or byinhibition of plasma membrane L-type Ca2+ channels A 3-day followup of treated cultures showed that NMR decreaseslong-term cell survival thus increasing the efficiency ofcytocidal treatments Mononuclear white blood cells are notsensitized to apoptosis by NMR showing that NMR mayincrease the differential cytotoxicity of antitumor drugs ontumor versus normal cells The authors suggested that thisstrong differential potentiating effect of NMR on tumorcell apoptosis may have important implications as in fact apossible adjuvant for antitumor therapies

5 Summary and Conclusions

In recent years an abundance of research papers reviewpapers and books has been published describing the possiblephysical and biological interactions of magnetic fields

Considering these articles comprehensively the con-clusions are as follows the primary cause of changes incells after incubation in external SMF is disruption of freeradicalmetabolism and elevation of their concentration Suchdisruption causes oxidative stress and as a result damagesion channels leading to changes in cell morphology andexpression of different genes and proteins and also changesin apoptosis and proliferation Moreover based on availabledata it was concluded that exposure to SMFs alone has noor extremely small effects on cell growth and genetic toxicityregardless of the magnetic density However in combinationwith other external factors such as ionizing radiation andsome chemicals such as cadmium there is evidence stronglysuggesting that an SMF modifies their effects Effects ofSMFs on apoptosis are a potentially interesting phenomenonHowever these effects often depended on a cell type andwere not found in various types of cells Many researchershave observed the effects of SMFs on tumor cells particularlythe inhibiting effects In order to reduce the toxicity andresistance of single anticancer drugs a variety of unifiedtreatments were requiredThe synergy of magnetic fields andanticancer drugs was one of the methods It provides a newstrategy for the effective treatment of cancer

These studies provide valuable insight into the phe-nomenon of biomagnetism and open new avenues for thedevelopment of newmedical applications Further studies arenecessary to explore the mechanisms of the SMF action inmore detail

References

[1] R Saunders ldquoStatic magnetic fields animal studiesrdquo Progress inBiophysics and Molecular Biology vol 87 no 2-3 pp 225ndash2392005

[2] M S Markov ldquolsquoBiological windowsrsquo a tribute toW Ross AdeyrdquoEnvironmentalist vol 25 no 2ndash4 pp 67ndash74 2005

[3] WRAdey ldquoModels ofmembranes of cerebral cells as substratesfor information storagerdquo BioSystems vol 8 no 4 pp 163ndash1781977


[4] W R Adey ldquoThe sequence and energetic of cell membranecoupling to intracellular enzyme systemsrdquo Bioelectrochemistryand Bioenergetics vol 15 no 3 pp 447ndash456 1986

[5] M S Markov ldquoElectromagnetic field influence onmembranesrdquoin Interfacial Phenomena in Biological System M Bender Edpp 171ndash192 Marcel Dekker 1991

[6] World Health Organization ldquoStatic Fieldsrdquo EnvironmentalHealth Criteria 232 Geneva Switzerland 2006

[7] A P Colbert J Souder and M Markov ldquoStatic magneticfield therapy methodological challenges to conducting clinicaltrialsrdquo Environmentalist vol 29 no 2 pp 177ndash185 2009

[8] A H Hashish M A El-Missiry H I Abdelkader and R HAbou-Saleh ldquoAssessment of biological changes of continuouswhole body exposure to static magnetic field and extremely lowfrequency electromagnetic fields in micerdquo Ecotoxicology andEnvironmental Safety vol 71 no 3 pp 895ndash902 2008

[9] M J McLean R R Holcomb AWWamil J D Pickett and AV Cavopol ldquoBlockade of sensory neuron action potentials bya static magnetic field in the 10mT rangerdquo Bioelectromagneticsvol 16 no 1 pp 20ndash32 1995

[10] M S Markov ldquoTherapeutic application of static magneticfieldsrdquo Environmentalist vol 27 no 4 pp 457ndash463 2007

[11] H Sahebjamei P Abdolmaleki and F Ghanati ldquoEffects of mag-netic field on the antioxidant enzyme activities of suspension-cultured tobacco cellsrdquo Bioelectromagnetics vol 28 no 1 pp42ndash47 2007

[12] G Zhao S Chen L Wang et al ldquoCellular ATP contentwas decreased by a homogeneous 85 T static magnetic fieldexposure role of reactive oxygen speciesrdquo Bioelectromagneticsvol 32 no 2 pp 94ndash101 2011

[13] S Ueno and T Shigemitsu ldquoBiological effects of static magneticfieldsrdquo in Handbook of Biological Effects of ElectromagneticFields Bioengineering andBiophysical Aspects of ElectromagneticFields F S Barnes and B Greenebaum Eds CRC Press BocaRaton Fla USA 3rd edition 2007

[14] S Ueno and K Harada ldquoExperimental difficulties in observingthe effects of magnetic fields on biological and chemicalprocessesrdquo IEEE Transactions on Magnetics vol 22 no 5 pp868ndash873 1986

[15] K AMcLauchlan andU E Steiner ldquoThe spin correlated radicalpair as a reaction intermediaterdquo Molecular Physics vol 73 no2 pp 241ndash263 1991

[16] J R Connor and S L Menzies ldquoCellular management of ironin the brainrdquo Journal of the Neurological Sciences vol 134supplement pp 33ndash44 1995

[17] W R Markesbery ldquoOxidative stress hypothesis in Alzheimerrsquosdiseaserdquo Free Radical Biology and Medicine vol 23 no 1 pp134ndash147 1997

[18] WH Koppenol ldquoTheHaber-Weiss cyclemdash70 years laterrdquoRedoxReport vol 6 no 4 pp 229ndash234 2001

[19] International Commission on Non-Ionizing Radiation Protec-tion (ICNIRP) ldquoGuidelines on limits of exposure to staticmagnetic fieldsrdquoHealth Physics vol 96 no 4 pp 504ndash514 2009

[20] N Mohtat F L Cozens T Hancock-Chen J C Scaiano JMcLean and J Kim ldquoMagnetic field effects on the behaviorof radicals in protein and DNA environmentsrdquo Photochemistryand Photobiology vol 67 no 1 pp 111ndash118 1998

[21] Q M Zhang M Tokiwa T Doi et al ldquoStrong static mag-netic field and the induction of mutations through elevatedproduction of reactive oxygen species in Escherichia coli soxRrdquoInternational Journal of Radiation Biology vol 79 no 4 pp 281ndash286 2003

[22] H Okano ldquoEffects of static magnetic fields in biology role offree radicalsrdquo Frontiers in Bioscience vol 13 no 16 pp 6106ndash6125 2008

[23] L Dini ldquoPhagocytosis of dying cells influence of smoking andstatic magnetic fieldsrdquo Apoptosis vol 15 no 9 pp 1147ndash11642010

[24] J Miyakoshi ldquoEffects of static magnetic fields at the cellularlevelrdquo Progress in Biophysics and Molecular Biology vol 87 no2-3 pp 213ndash223 2005

[25] AGNIR ldquoELF electromagnetic fields and the risk of cancerReport of an Advisory Group on Non-Ionising RadiationrdquoDocuments of the NRPB vol 12 no 1 2001

[26] WHO ldquoMagnetic Fields Environmental Health Criteria 69rdquoWorld Health Organisation Geneva Switzerland 1987

[27] C I Kowalczuk Z J Sienkiewicz and R D Saunders ldquoBiolog-ical effects of exposure to non-ionising electromagnetic fieldsand radiation I Static electric and magnetic fieldsrdquo Tech RepNRPB-R238 NRPB Chilton Wis USA 1991

[28] ICNIRP ldquoGuidelines on limits of exposure to static magneticfieldsrdquo Health Physics vol 66 no 1 pp 100ndash106 1994

[29] ICNIRP ldquoBiological effects of static and ELF electric andmagnetic fieldsrdquo in Proceedings of the International Seminaron Biological Effects of Static and ELF Electric and MagneticFields and Related Health Risks Bologna Italy (ICNIRP rsquo97)R Matthes J H Bernhardt and M H Repacholi Eds vol 4Markl-Druck Munchen Germany 1997

[30] M H Repacholi and B Greenebaum ldquoInteraction of static andextremely low frequency electric andmagnetic fields with livingsystems health effects and research needsrdquo Bioelectromagneticsvol 20 no 3 pp 133ndash160 1999

[31] International Agency for Research on Cancer (IARC) IARCMonographs on the Evaluation of Carcinogenic Risks to HumansNon-Ionising Radiation Part 1 Static and Extremely Low Fre-quency (ELF) Electric and Magnetic Fields vol 80 IARC LyonFrance 2002

[32] ICNIRP ldquoExposure to static and low frequency electromag-netic fieldsrdquo in Biological Effects and Health Consequences(0ndash100 kHz) (ICNIRP rsquo03) R Matthes A F McKinlay J HBernhardt P Vecchia and B Veyret Eds vol 13Markl-DruckMunchen Germany 2003

[33] A FMcKinlay S GAllen R Cox et al ldquoReviewof the scientificevidence for limiting exposure to electromagnetic fields (0ndash300GHz)rdquo Documents of the NRPB vol 15 no 3 2004

[34] L Dini and L Abbro ldquoBioeffects of moderate-intensity staticmagnetic fields on cell culturesrdquoMicron vol 36 no 3 pp 195ndash217 2005

[35] J L Phillips N P Singh andH Lai ldquoElectromagnetic fields andDNAdamagerdquo Pathophysiology vol 16 no 2-3 pp 79ndash88 2009

[36] S Ueno and H Okano ldquoStatic low-frequency and pulsedmagnetic fields in biological systemsrdquo in Electromagnetic Fieldsin Biological Systems chapter 3 pp 115ndash196 Taylor amp FrancisGroup LLC 2012

[37] S Engstrom ldquoMagnetic field effects on free radical reactionsin biologyrdquo in Handbook of Biological Effects of ElectromagneticFields Bioengineering andBiophysical Aspects of ElectromagneticFields F S Barnes and B Greenebaum Eds CRC Press BocaRaton Fla USA 3rd edition 2007

[38] C Nathan ldquoNitric oxide as a secretory product of mammaliancellsrdquoThe FASEB Journal vol 6 no 12 pp 3051ndash3064 1992

[39] H M Lander ldquoAn essential role for free radicals and derivedspecies in signal transductionrdquo The FASEB Journal vol 11 no2 pp 118ndash124 1997


[40] V J Thannickal and B L Fanburg ldquoReactive oxygen species incell signalingrdquo American Journal of Physiology vol 279 no 6pp L1005ndashL1028 2000

[41] B Brocklehurst and K A McLauchlan ldquoFree radical mecha-nism for the effects of environmental electromagnetic fields onbiological systemsrdquo International Journal of Radiation Biologyvol 69 no 1 pp 3ndash24 1996

[42] S Amara H Abdelmelek C Garrel et al ldquoEffects of subchronicexposure to static magnetic field on testicular function in ratsrdquoArchives of Medical Research vol 37 no 8 pp 947ndash952 2006

[43] S Amara T Douki C Garel et al ldquoEffects of static magneticfield exposure on antioxidative enzymes activity and DNA inrat brainrdquo General Physiology and Biophysics vol 28 no 3 pp260ndash265 2009

[44] S Amara T Douki J L Ravanat et al ldquoInfluence of a staticmagnetic field (250mT) on the antioxidant response and DNAintegrity in THP1 cellsrdquo Physics in Medicine and Biology vol 52no 4 pp 889ndash898 2007

[45] S Chater H Abdelmelek T Douki et al ldquoExposure to staticmagnetic field of pregnant rats induces hepatic GSH elevationbut not oxidative DNA damage in liver and kidneyrdquo Archives ofMedical Research vol 37 no 8 pp 941ndash946 2006

[46] S Ghodbane S Amara C Garrel et al ldquoSelenium supplemen-tation ameliorates static magnetic field-induced disorders inantioxidant status in rat tissuesrdquo Environmental Toxicology andPharmacology vol 31 no 1 pp 100ndash106 2011

[47] B Kula A Sobczak and R Kuska ldquoEffects of static and ELFmagnetic fields on free-radical processes in rat liver and kidneyrdquoElectromagnetic Biology and Medicine vol 19 no 1 pp 99ndash1052000

[48] M Zmyslony J Jajte E Rajkowska and S Szmigielski ldquoWeak(5MT) staticmagnetic field stimulates lipid peroxidation in iso-lated rat livermicrosomes in vitrordquoElectro- andMagnetobiologyvol 17 no 2 pp 109ndash113 1998

[49] S Ghodbane S Amara J Arnaud et al ldquoEffect of seleniumpre-treatment on plasma antioxidant vitamins A (retinol) and e(120572-tocopherol) in staticmagnetic field-exposed ratsrdquoToxicologyand Industrial Health vol 27 no 10 pp 949ndash955 2011

[50] S Amara H Abdelmelek C Garrel et al ldquoZinc supplemen-tation ameliorates static magnetic field-induced oxidative stressin rat tissuesrdquo Environmental Toxicology and Pharmacology vol23 no 2 pp 193ndash197 2007

[51] J Walleczek and R P Liburdy ldquoNonthermal 60Hz sinusoidalmagnetic-field exposure enhances 45Ca2+ uptake in rat thymo-cytes dependence onmitogen activationrdquo FEBS Letters vol 271no 1-2 pp 157ndash160 1990

[52] H Abdelmelek A Molnar S Servais et al ldquoSkeletal muscleHSP72 and norepinephrine response to static magnetic field inratrdquo Journal of Neural Transmission vol 113 no 7 pp 821ndash8272006

[53] S Chater H Abdelmelek D Couton et al ldquoEffects of sub-acuteexposure to magnetic field on synthesis of plasma corticos-terone and liver metallothionein levels in female ratsrdquo PakistanJournal of Medical Sciences vol 20 no 3 pp 219ndash223 2004

[54] S Chater H Abdelmelek D Couton V JoulinM Sakly and KBen Rhouma ldquoSub-acute exposure to magnetic field inducedapoptosis in thymus female ratsrdquo Pakistan Journal of MedicalSciences vol 21 no 3 pp 292ndash297 2005

[55] D Agay R A Anderson C Sandre et al ldquoAlterations ofantioxidant trace elements (Zn Se Cu) and related metallo-enzymes in plasma and tissues following burn injury in ratsrdquoBurns vol 31 no 3 pp 366ndash371 2005

[56] D Duda J Grzesik and K Pawlicki ldquoChanges in liver andkidney concentration of coppermanganese cobalt and iron ratsexposed to static and low-frequency (50Hz) magnetic fieldsrdquoJournal of Trace Elements and Electrolytes in Health and Diseasevol 5 no 3 pp 181ndash186 1991

[57] A S Monfared S G Jorsaraei and R Abdi ldquoProtective effectsof vitamins C and E on spermatogenesis of 15 tesla magneticfield exposed ratsrdquo Journal of Magnetic Resonance Imaging vol30 no 5 pp 1047ndash1051 2009

[58] J Jajte M Zmyslony and E Rajkowska ldquoProtective effect ofmelatonin and vitamin E against prooxidative action of ironions and static magnetic fieldrdquo Medycyna Pracy vol 54 no 1pp 23ndash28 2003

[59] K Sullivan A K Balin and R G Allen ldquoEffects of staticmagnetic fields on the growth of various types of human cellsrdquoBioelectromagnetics vol 32 no 2 pp 140ndash147 2011

[60] H Kabuto I Yokoi N Ogawa A Mori and R P LiburdyldquoEffects ofmagnetic fields on the accumulation of thiobarbituricacid reactive substances induced by iron salt andH

2O2inmouse

brain homogenates or phosphotidylcholinerdquo Pathophysiologyvol 7 no 4 pp 283ndash288 2001

[61] S Amara C Garrel A Favier K Ben Rhouma M Sakly andH Abdelmelek ldquoEffect of static magnetic field andor cadmiumin the antioxidant enzymes activity in rat heart and skeletalmusclerdquo General Physiology and Biophysics vol 28 no 4 pp414ndash419 2009

[62] S Amara T Douki C Garrel et al ldquoEffects of static magneticfield and cadmium on oxidative stress and DNA damage inrat cortex brain and hippocampusrdquo Toxicology and IndustrialHealth vol 27 no 2 pp 99ndash106 2011

[63] S Chater T Douki A Favier C Garrel M Sakly and HAbdelmelek ldquoInfluence of static magnetic field on cadmiumtoxicity study of oxidative stress and DNA damage in pregnantrat tissuesrdquo Electromagnetic Biology and Medicine vol 27 no 4pp 393ndash401 2008

[64] O Sirmatel C Sert F Sirmatel S Selek and B Yokus ldquoTotalantioxidant capacity total oxidant status and oxidative stressindex in the men exposed to 15 T static magnetic fieldrdquoGeneralPhysiology and Biophysics vol 26 no 2 pp 86ndash90 2007

[65] M Satoh Y Tsuji Y Watanabe et al ldquoMetallothionein contentincreased in the liver of mice exposed to magnetic fieldsrdquoArchives of Toxicology vol 70 no 5 pp 315ndash318 1996

[66] Y Watanabe M Nakagawa and Y Miyakoshi ldquoEnhancementof lipid peroxidation in the liver of mice exposed to magneticfieldsrdquo Industrial Health vol 35 no 2 pp 285ndash290 1997

[67] F Cintolesi T Ritz C W M Kay C R Timmel and P J HoreldquoAnisotropic recombination of an immobilized photoinducedradical pair in a 50-120583T magnetic field a model avian photo-magnetoreceptorrdquoChemical Physics vol 294 no 3 pp 385ndash3992003

[68] O Efimova and P J Hore ldquoRole of exchange and dipolarinteractions in the radical pair model of the avian magneticcompassrdquoBiophysical Journal vol 94 no 5 pp 1565ndash1574 2008

[69] R W Kay ldquoGeomagnetic storms association with incidenceof depression as measured by hospital admissionrdquo The BritishJournal of Psychiatry vol 164 no 3 pp 403ndash409 1994

[70] M Berk S Dodd and M Henry ldquoDo ambient electromagneticfields affect behaviour A demonstration of the relationshipbetween geomagnetic storm activity and suiciderdquo Bioelectro-magnetics vol 27 no 2 pp 151ndash155 2006


[71] J R Gray C H Frith and J D Parker ldquoIn vivo enhancement ofchemotherapywith static electric ormagnetic fieldsrdquoBioelectro-magnetics vol 21 no 8 pp 575ndash583 2000

[72] M Zmyslony J Palus J Jajte E Dziubaltowska and ERajkowska ldquoDNA damage in rat lymphocytes treated in vitrowith iron cations and exposed to 7mTmagnetic fields (static or50Hz)rdquoMutation Research vol 453 no 1 pp 89ndash96 2000

[73] J Jajte J Grzegorczyk M Zmysacute and E RajkowskaldquoEffect of 7mT static magnetic field and iron ions on ratlymphocytes apoptosis necrosis and free radical processesrdquoBioelectrochemistry vol 57 no 2 pp 107ndash111 2002

[74] B Tenuzzo C Vergallo and L Dini ldquoEffect of 6mT staticmagnetic field on the bcl-2 bax p53 and hsp70 expression infreshly isolated and in vitro aged human lymphocytesrdquo Tissueand Cell vol 41 no 3 pp 169ndash179 2009

[75] C Fanelli S Coppola R Barone et al ldquoMagnetic fields increasecell survival by inhibiting apoptosis via modulation of Ca2+influxrdquoThe FASEB Journal vol 13 no 1 pp 95ndash102 1999

[76] M de Nicola S Cordisco C Cerella et al ldquoMagnetic fieldsprotect from apoptosis via redox alterationrdquo Annals of the NewYork Academy of Sciences vol 1090 pp 59ndash68 2006

[77] D Flipo M Fournier C Benquet et al ldquoIncreased apoptosischanges in intracellular Ca2+ and functional alterations inlymphocytes and macrophages after in vitro exposure to staticmagnetic fieldrdquo Journal of Toxicology and Environmental HealthA vol 54 no 1 pp 63ndash76 1998

[78] R Ishisaka T Kanno Y Inai et al ldquoEffects of a magnetic fieldson the various functions of subcellular organelles and cellsrdquoPathophysiology vol 7 no 2 pp 149ndash152 2000

[79] L Teodori J Grabarek P Smolewski et al ldquoExposure of cellsto static magnetic field accelerates loss of integrity of plasmamembrane during apoptosisrdquo Cytometry vol 49 no 3 pp 113ndash118 2002

[80] L Teodori W Gohde M G Valente et al ldquoStatic magneticfields affect calcium fluxes and inhibit stress-induced apoptosisin human glioblastoma cellsrdquo Cytometry vol 49 no 4 pp 143ndash149 2002

[81] L Teodori M C Albertini F Uguccioni et al ldquoStatic magneticfields affect cell size shape orientation and membrane surfaceof human glioblastoma cells as demonstrated by electron opticand atomic force microscopyrdquo Cytometry A vol 69 no 2 pp75ndash85 2006

[82] L Potenza C Martinelli E Polidori et al ldquoEffects of a 300mTstatic magnetic field on human umbilical vein endothelial cellsrdquoBioelectromagnetics vol 31 no 8 pp 630ndash639 2010

[83] Q Hao C Wenfang A Xia et al ldquoEffects of a moderate-intensity static magnetic field and adriamycin on K562 cellsrdquoBioelectromagnetics vol 32 no 3 pp 191ndash199 2011

[84] A S Sarvestani P Abdolmaleki S J Mowla et al ldquoStaticmagnetic fields aggravate the effects of ionizing radiation on cellcycle progression in bone marrow stem cellsrdquo Micron vol 41no 2 pp 101ndash104 2010

[85] J McCann F Dietrich C Rafferty and A Martin ldquoA criticalreview of the genotoxic potential of electric and magneticfieldsrdquoMutation Research vol 297 no 1 pp 61ndash95 1993

[86] Y Suzuki M Ikehata K Nakamura et al ldquoInduction ofmicronuclei in mice exposed to static magnetic fieldsrdquo Muta-genesis vol 16 no 6 pp 499ndash501 2001

[87] J W Lee M S Kim Y J Kim Y J Choi Y Lee and H WChung ldquoGenotoxic effects of 3 T magnetic resonance imagingin cultured human lymphocytesrdquo Bioelectromagnetics vol 32no 7 pp 535ndash542 2011

[88] W G Schreiber E M Teichmann I Schiffer et al ldquoLack ofmutagenic and co-mutagenic effects of magnetic fields duringmagnetic resonance imagingrdquo Journal of Magnetic ResonanceImaging vol 14 no 6 pp 779ndash788 2001

[89] N F Schwenzer R Bantleon B Maurer et al ldquoDetection ofDNA double-strand breaks using 120574H2AX after MRI exposureat 3 Tesla an in vitro studyrdquo Journal of Magnetic ResonanceImaging vol 26 no 5 pp 1308ndash1314 2007

[90] H Okonogi M Nakagawa and Y Tsuji ldquoThe effects of a 47tesla static magnetic field on the frequency of micronucleatedcells induced by mitomycin Crdquo The Tohoku Journal of Experi-mental Medicine vol 180 no 3 pp 209ndash215 1996

[91] T Kimura K Takahashi Y Suzuki et al ldquoThe effect ofhigh strength static magnetic fields and ionizing radiation ongene expression and DNA damage in Caenorhabditis elegansrdquoBioelectromagnetics vol 29 no 8 pp 605ndash614 2008

[92] T Koana M O Okada M Ikehata and M NakagawaldquoIncrease in the mitotic recombination frequency inDrosophilamelanogaster by magnetic field exposure and its suppression byvitamin E supplementrdquo Mutation Research vol 373 no 1 pp55ndash60 1997

[93] U Graf F E Wurgler and A J Katz ldquoSomatic mutation andrecombination test in Drosophila melanogasterrdquo EnvironmentalMutagenesis vol 6 no 2 pp 153ndash188 1984

[94] M Ikehata T Koana Y Suzuki H Shimizu andM NakagawaldquoMutagenicity and co-mutagenicity of static magnetic fieldsdetected by bacterial mutation assayrdquo Mutation Research vol427 no 2 pp 147ndash156 1999

[95] T Nakahara H Yaguchi M Yoshida and J Miyakoshi ldquoEffectsof exposure of CHO-K1 cells to a 10-T static magnetic fieldrdquoRadiology vol 224 no 3 pp 817ndash822 2002

[96] S Tofani D Barone M Berardelli et al ldquoStatic and ELF mag-netic fields enhance the in vivo anti-tumor efficacy of cis-platinagainst lewis lung carcinoma but not of cyclophosphamideagainst B16 melanotic melanomardquo Pharmacological Researchvol 48 no 1 pp 83ndash90 2003

[97] R G Sun W F Chen H Qi et al ldquoBiologic effects of SMF andpaclitaxel on K562 human leukemia cellsrdquo General Physiologyand Biophysics vol 31 no 1 pp 1ndash10 2012

[98] S Strieth D Strelczyk M E Eichhorn et al ldquoStatic magneticfields induce blood flow decrease and platelet adherence intumor microvesselsrdquo Cancer Biology ampTherapy vol 7 no 6 pp814ndash819 2008

[99] D Strelczyk M E Eichhorn S Luedemann et al ldquoStaticmagnetic fields impair angiogenesis and growth of solid tumorsin vivordquo Cancer Biology and Therapy vol 8 no 18 pp 1756ndash1762 2009

[100] W F Chen H Qi R G Sun Y Liu K Zhang and J Q LiuldquoStatic magnetic fields enhanced the potency of cisplatin onK562 cellsrdquo Cancer Biotherapy and Radiopharmaceuticals vol25 no 4 pp 401ndash408 2010

[101] Y Liu H Qi R G Sun and W F Chen ldquoAn investigationinto the combined effect of static magnetic fields and differentanticancer drugs on K562 cell membranesrdquo Tumori vol 97 no3 pp 386ndash392 2011

[102] R R Raylman A C Clavo and R LWahl ldquoExposure to strongstatic magnetic field slows the growth of human cancer cells invitrordquo Bioelectromagnetics vol 17 no 5 pp 358ndash363 1996

[103] A Chionna B Tenuzzo E Panzarini M B Dwikat L Abbroand L Dini ldquoTime dependent modifications of Hep G2 cellsduring exposure to static magnetic fieldsrdquo Bioelectromagneticsvol 26 no 4 pp 275ndash286 2005


[104] S W Feng Y J Lo W J Chang et al ldquoStatic magnetic fieldexposure promotes differentiation of osteoblastic cells grown onthe surface of a poly-L-lactide substraterdquo Medical amp BiologicalEngineering amp Computing vol 48 no 8 pp 793ndash798 2010

[105] S H Hsu and J C Chang ldquoThe static magnetic field acceleratesthe osteogenic differentiation andmineralization of dental pulpcellsrdquo Cytotechnology vol 62 no 2 pp 143ndash155 2010

[106] C F Martino L Portelli K McCabe M Hernandez and FBarnes ldquoReduction of the Earthrsquos magnetic field inhibits growthrates of model cancer cell linesrdquo Bioelectromagnetics vol 31 no8 pp 649ndash655 2010

[107] J C Yang S Y Lee C A Chen C T Lin C C Chen and HM Huang ldquoThe role of the calmodulin-dependent pathway instatic magnetic field-induced mechanotransductionrdquo Bioelec-tromagnetics vol 31 no 4 pp 255ndash261 2010

[108] J Sabo L Mirossay L Horovcak M Sarissky A Mirossay andJ Mojzis ldquoEffects of static magnetic field on human leukemiccell line HL-60rdquo Bioelectrochemistry vol 56 no 1-2 pp 227ndash231 2002

[109] L Ghibelli C Cerella S Cordisco et al ldquoNMR exposuresensitizes tumor cells to apoptosisrdquo Apoptosis vol 11 no 3 pp359ndash365 2006

Submit your manuscripts athttpwwwhindawicom

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Anatomy Research International

PeptidesInternational Journal of


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International Journal of

Volume 2014

Zoology


Molecular Biology International

GenomicsInternational Journal of


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BioinformaticsAdvances in

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Signal TransductionJournal of


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ArchaeaHindawi Publishing Corporationhttpwwwhindawicom Volume 2014


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Volume 2014

Stem CellsInternational



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Microbiology


Previous research showed that SMF influences biologicalsystem in a way that causes proinflammatory changes as wellas an increase in production of reactive oxygen species (ROS)[11 12] Throughout the past decades there have been severalexperimental results describing the effects of MFs on radicalpair recombination

As reviewed recently byUeno and Shigemitsu [13] severalbiophysical and biochemical effects can be expected whenbiological systems are simultaneously exposed to SMFs andother forms of energy such as light and radiation [14 15]

Although there is much speculation about this role theprimary mechanism is thought to be the result of oxidativestress that is free radical generation via Fenton reactionwhich is the iron-catalyzed oxidation of hydrogen peroxide(H2O2) [16ndash18]

Recent advance of biological science and technology canhelp us understand MF effects more clearly Studies on thebiological effects of MFs have resulted in significant develop-ments in themedical applications of SMF aswell as EMF afterthe development of high-strength superconducting magnetsThe mainstays of such medical applications are transcranialmagnetic stimulation (TMS) andMRIThese techniques havealso contributed much to the amazing progress made inunderstanding brain functions A guideline for exposure ofthe human body to SMFs set by the international commissionon nonionizing radiation protection (ICNIRP) [19] suggests2 T as the ceiling value for body parts except for arms andlegs in occupational exposure In the application of clinicalMRI the current exposure level is confirmed to be less than orequal to 2 T In SMFs at this strength it is not feasible to obtainresonance images except for hydrogen atoms There areseveral reports that strong SMF effects play significant rolesin endogenous and exogenous ROS generations Based onadvanced studies of SMF effects on oxidative stress reactionsthe potentially hazardous effect of SMF on living organisms isthat exposure to SMF can increase the activity concentrationand life time of paramagnetic free radicals whichmight causeoxidative stress genetic mutation andor apoptosis [20ndash23] In particular SMF exposure initiates an iron-mediatedprocess that increases free radical formation in brain cellsleading to the breaking of DNA strands and cell death

Genotoxic effects of exposure to static magnetic fieldshave been mostly examined in cell cultures [24] Few invivo studies of genotoxicity or possible effects on othercarcinogenic processes have been carried out Animal studiesare often used in the evaluation of suspected human car-cinogens [25] either screening for an increased incidence ofspontaneous tumors or of the incidence of tumors induced byknown carcinogens

The earlier literature has been summarized byWHO [26]Kowalczuk et al [27] and ICNIRP [28 29] Repacholi andGreenebaum [30] IARC [31] ICNIRP [32] McKinlay et al[33] andDini andAbbro [34] whilstmore recent studies havebeen reviewed by Okano [22] Phillips et al [35] and Uenoand Okano [36]

The focus of this review is on recent studies where pos-sible These studies are covered under three main sectionsfree radical generation and oxidative stress apoptosis andgenotoxicity and cancer

The objective of this review is to describe and shed lighton some of the most recent information on the biologicaleffects and medical applications of magnetic fields A dis-cussion of possible implications of these effects on biologicalsystems is also provided

2 Oxidative Stress

Biological free radicals are most commonly oxygen ornitrogen based with an unpaired electron leading to theterms ROS such as superoxide anion (O2minus) hydroxyl radical(OH∙) and singlet oxygen (

1O2) or ldquoreactive nitrogen species

(RNS)rdquo such as nitric oxide (NO) [37]TheROS andRNSplaysignificant roles in immunological defense [38] intracellularsignaling [39] and intercellular communication [40] It isassumed that SMF could change the lifetime of radical pairsyields of cage products and escape products If an SMF affectscells through the radical pair mechanism an SMF influencesthe spin of electrons in free radicals which may lead tochanges in chemical reaction kinetics and possibly alteringcellular function [41]

21 Moderate-Intensity Static Magnetic Fields and OxidativeStress There are several reports showing that moderate SMFcould influence the ROS modulation (generationreduction)from enzymatic reactions in cell-free solutions The SMFeffects also play significant roles in the endogenous andexogenous ROS modulation in biological systems in vitroand in vivo

Amara et al [42] investigated the effect of SMF expo-sure on testicular function and antioxidant status in ratsExposure to SMF (128mT 1 hday for 30 days) has noeffect on epididymal sperm count spermatozoa motility andgenital organ weight In contrast SMF induces an increaseof malondialdehyde (MDA) in the testis In the gonadSMF decreases the catalase (CAT) glutathione peroxidase(GPx) and mitochondrial Mn-superoxide dismutase (Mn-SOD) activities However cytosolic CuZn-SOD activity isunaffected

The latter group also investigated the effects of SMF(128mT 1 hday during 30 consecutive days) exposure on theantioxidative enzymes activity and MDA concentration inmale rat brain [43] The exposure of rats to SMF decreasedthe GPx CuZn-SOD and CAT activities in frontal cortexThe same treatment decreased the CuZn-SOD and Mn-SOD activities in hippocampus However the glutathionelevels remained unchanged in both brain structures In thehippocampus SMF-exposure increasedMDA concentrationThese results indicated that exposure to SMF induced oxida-tive stress in rat hippocampus and frontal cortex

SMF exposure alters antioxidant enzyme activity and thelabile zinc fraction in THP1 cells (monocyte line) [44] Cellculture flasks were exposed to SMF (250mT) during 1 h 2 hand 3 h Cell viability was slightly lower in SMF-exposedgroups compared to a sham-exposed group However SMFexposure failed to alter MDA GPx CAT and SOD levelseven by 3 h of exposition Cells stained with zinc-specificfluorescent probes zinpyr-1 showed a decrease of labile zinc





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2O2induced a























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References































































2O2inmouse




























































Volume 2014

Zoology






















Advances in

Virolog y



Volume 2014




Enzyme Research



Microbiology





2SeO3 02mgL















3 In contrast






















4


4injection









2





2(10mgmL)


2 there





2 to 25ndash





2O2 The H

2O2induced a























4 Cancer Studies


















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2O2inmouse




























































Volume 2014

Zoology






















Advances in

Virolog y



Volume 2014




Enzyme Research



Microbiology




















4


4injection









2





2(10mgmL)


2 there





2 to 25ndash





2O2 The H

2O2induced a























4 Cancer Studies


















References































































2O2inmouse




























































Volume 2014

Zoology






















Advances in

Virolog y



Volume 2014




Enzyme Research



Microbiology



2





2(10mgmL)


2 there





2 to 25ndash





2O2 The H

2O2induced a























4 Cancer Studies


















References































































2O2inmouse




























































Volume 2014

Zoology






















Advances in

Virolog y



Volume 2014




Enzyme Research



Microbiology















4 Cancer Studies


















References































































2O2inmouse




























































Volume 2014

Zoology






















Advances in

Virolog y



Volume 2014




Enzyme Research



Microbiology











References































































2O2inmouse




























































Volume 2014

Zoology






















Advances in

Virolog y



Volume 2014




Enzyme Research



Microbiology




























































2O2inmouse




























































Volume 2014

Zoology






















Advances in

Virolog y



Volume 2014




Enzyme Research



Microbiology

















































Volume 2014

Zoology






















Advances in

Virolog y



Volume 2014




Enzyme Research



Microbiology