Hindawi Publishing CorporationBioMed Research InternationalVolume 2013, Article ID 602987, 12 pageshttp://dx.doi.org/10.1155/2013/602987Review ArticleBioeffects of Static Magnetic Fields: Oxidative Stress, GenotoxicEffects, and Cancer StudiesSoumaya Ghodbane, Aida Lahbib, Mohsen Sakly, and Hafedh AbdelmelekUniversit e de Carthage, Laboratoire de Physiologie Int egr ee, Facult e des Sciences de Bizerte, 7021 Jarzouna, TunisiaCorrespondence should be addressed to Soumaya Ghodbane; ghodhbanes@yahoo.frReceived 24 April 2013; Revised 11 July 2013; Accepted 11 July 2013Academic Editor: Ali KhraibiCopyright 2013 Soumaya Ghodbane et al. Tis 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.Te interaction of static magnetic felds (SMFs) with living organisms is a rapidly growing feld of investigation. Te magneticfelds (MFs) efect 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, and/or apoptosis. Current evidence suggests that cell proliferation can be infuencedby a treatment with both SMFs and anticancer drugs. It has been recently found that SMFs can enhance the anticancer efect ofchemotherapeutic drugs; this may provide a new strategy for cancer therapy. Tis review focuses on our own data and other datafrom the literature of SMFs bioefects. Tree main areas of investigation have been covered: free radical generation and oxidativestress, apoptosis and genotoxicity, and cancer. Afer an introduction on SMF classifcation and medical applications, the basicphenomena to understand the bioefects are described. Te scientifc literature is summarized, integrated, and critically analyzedwith the help of authoritative reviews by recognized experts; international safety guidelines are also cited.1. IntroductionLiving organisms are continuously exposed to the naturalgeomagnetic feld of around 2070 T that exists over thesurface of the Earth and which is implicated inthe orientationand migration of certain animal species [1].Duringevolution, livingorganismsdevelopedspecifcmechanisms for perception of natural electric and magneticfelds.Tese mechanisms require specifc combinations ofphysical parameters of the applied feld to be detected bybiological systems. In order words, the windows are meansby which discrete MFs are detected by biological systems.Dependingonthe level of structural organizationthesemechanisms of detection and response may be seen at difer-ent levels, for example, at membrane, cellular, or tissue levels.Sometimes the windows function via signal transductioncascade, brainactivity, orthecentral nervoussystem[2].Tesensitivityofthebiological systemstoweakMFhasbeendescribedelsewhere[35], mainlyinrespecttothedependence of bioefects on the amplitude or the frequencyof applied felds.Te 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]. Terefore, it hasbecome necessary to systematically elucidate the infuenceof MFs on the body. In an attempt to explain the biologicalefects of SMFs, it is useful to classify them as weak (5 T).SMFs are time-independent felds whose intensity couldbe spatially dependent. Tere are four SMFparametersrelevant for the interaction with a biological system: targettissue(s), magnet characteristics, magnet support device, anddosingregimen[7]. SMFsaredifcult toshieldandcanfreelypenetratebiological tissues[8]. However, not onlythefeldintensity, but alsothegradient of thefeldhasimportant roleinbiological efectsof SMF[9, 10]. SMFcaninteractdirectlywithmovingcharges(ions, proteins,etc.) and magnetic materials found in tissues through severalphysical mechanisms [6].2 BioMed Research InternationalPrevious research showed that SMF infuences biologicalsystemin a way that causes proinfammatory changes, as wellas an increase in production of reactive oxygen species (ROS)[11, 12]. Troughout the past decades, there have been severalexperimental results describing the efects of MFs on radicalpair recombination.As reviewedrecently by Ueno andShigemitsu[13], severalbiophysical and biochemical efects 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 reaction,which is the iron-catalyzed oxidation of hydrogen peroxide(H2O2) [1618].Recent advance of biological science and technology canhelp us understand MF efects more clearly. Studies on thebiological efects of MFs have resulted in signifcant develop-ments in the medical applications of SMF as well as EMF, aferthe development of high-strength superconducting magnets.Te mainstays of such medical applications are transcranialmagnetic stimulation(TMS) and MRI. Tese techniques havealsocontributedmuchtotheamazingprogressmadeinunderstanding 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 confrmedto be less thanorequal to 2 T. In SMFs at this strength it is not feasible to obtainresonanceimages, except for hydrogenatoms. Tereareseveral reports that strong SMF efects play signifcant rolesin endogenous and exogenous ROS generations. Based onadvanced studies of SMF efects on oxidative stress reactions,the potentially hazardous efect of SMF on living organisms isthat exposure to SMF can increase the activity, concentration,and life time of paramagnetic free radicals, which might causeoxidativestress, geneticmutation, and/or apoptosis [2023]. In particular, SMF exposure initiates an iron-mediatedprocess that increases free radical formation in brain cells,leading to the breaking of DNA strands and cell death.Genotoxic efects of exposure to static magnetic feldshavebeenmostlyexaminedincell cultures[24]. Fewinvivostudies of genotoxicityor possible efects onothercarcinogenic processes have been carried out. Animal studiesare ofen 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.Te earlier literature has been summarized by WHO[26],Kowalczuk et al. [27] and ICNIRP [28, 29], Repacholi andGreenebaum [30], IARC [31], ICNIRP [32], McKinlay et al.[33], and Dini and Abbro [34] whilst more recent studies havebeen reviewed by Okano [22], Phillips et al. [35], and Uenoand Okano [36].Te focus of this review is on recent studies, where pos-sible. Tese studies are covered under three main sections:free radical generation and oxidative stress, apoptosis andgenotoxicity, and cancer.Te objective of this review is to describe and shed lighton some of the most recent information on the biologicalefects and medical applications of magnetic felds. A dis-cussion of possible implications of these efects on biologicalsystems is also provided.2. Oxidative StressBiological free radicals are most commonly oxygen ornitrogenbasedwithanunpairedelectron, leadingtotheterms ROS, such as superoxide anion (O2), hydroxyl radical(OH) and singlet oxygen (1O2), or reactive nitrogen species(RNS), such as nitric oxide (NO) [37]. Te ROS and RNS playsignifcant roles in immunological defense [38], intracellularsignaling [39], and intercellular communication [40]. It isassumed that SMF could change the lifetime of radical pairs,yields of cage products, and escape products. If anSMF afectscells through the radical pair mechanism, an SMF infuencesthespinof electronsinfreeradicals, whichmayleadtochanges in chemical reaction kinetics and possibly alteringcellular function [41].2.1. Moderate-Intensity Static Magnetic Fields and OxidativeStress. Tere are several reports showing that moderate SMFcould infuence the ROS modulation (generation/reduction)fromenzymaticreactionsincell-freesolutions. TeSMFefects alsoplaysignifcant roles intheendogenous andexogenous ROS modulation in biological systems, in vitroand in vivo.Amara et al. [42] investigated the efect of SMF expo-sureontesticularfunctionandantioxidantstatusinrats.Exposure toSMF(128 mT; 1 h/day for 30days) has noefect on epididymal sperm count, spermatozoa motility, andgenital organ weight. In contrast, SMF induces an increaseof malondialdehyde (MDA) inthe testis. Inthe gonad,SMF decreases the catalase (CAT), glutathione peroxidase(GPx), and mitochondrial Mn-superoxide dismutase (Mn-SOD)activities. However, cytosolicCuZn-SODactivityisunafected.Telatter groupalsoinvestigatedtheefects of SMF(128 mT, 1 h/day during 30 consecutive days) exposure on theantioxidative enzymes activity and MDA concentration inmale rat brain [43]. Te exposure of rats to SMF decreasedthe GPx, CuZn-SOD, and CAT activities in frontal cortex.Tesametreatment decreasedtheCuZn-SODandMn-SODactivitiesinhippocampus. However, theglutathionelevels remained unchanged in both brain structures. In thehippocampus, SMF-exposure increased MDAconcentration.Tese 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 fasks were exposed to SMF (250 mT) during 1 h, 2 h,and3 h. Cell viabilitywasslightlylowerinSMF-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-specifcfuorescent probes zinpyr-1 showed a decrease of labile zincBioMed Research International 3fractioninall groups exposedto SMF. SMFexposure (250 mT,during 3 h) did not cause oxidative stress in THP1 cells butaltered the intracellular labile zinc fraction.Chateretal. [45]evaluatedtheefectsofexposuretoSMF on some parameters indicative of oxidative stress inpregnant rat.Exposure to SMF (128 mT;1 h/day from day6 to day 19 of pregnancy) failed to alter plasma MDA andGPx activity. Moreover the same treatment did not alter liverconcentration of MDAand kidney activities of GPx CAT andSOD. By contrast, SMF induced an increase of liver GSHcontent. Similar results were reported by Ghodbane et al. [46]who show that liver GSH concentrations were signifcantlyhigher in SMF exposed rats than in the controls, indicatingan adaptive mechanism to electromagnetic pollution. GSHlevels canbe increaseddue to anadaptive mechanismto slightoxidative stress through an increase in its synthesis. However,a severe oxidative stress may decrease GSH levels due to theloss of adaptive mechanisms and the oxidation of GSH toGSSG.Exposure to SMF (128 mT; 1 h/day for 5 days) induces adecrease of selenium levels in kidney, muscle, and brain witha decrease of GPx activities inkidney and muscle. By contrast,SMFexposureincreasedtotal GSHlevelsandtotal SODactivities in liver, while glutathione reductase (GR) activity isunafected. Selenium supplementation (Na2SeO3, 0.2 mg/L,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]. Tus, subacute exposure to SMF altered the antioxidantresponse by decreasing tissues seleniumcontents, whileselenium supplementation ameliorates antioxidant capacityinrat exposedtoSMF. Regardingthe 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 diferent cells and organs[22, 47, 48]. However, Ghodbaneetal. [49]showedthatSMF exposure failed to alter plasma TBARs and total thiolgroups, indicating an adaptive mechanism to slight oxidativestress caused by electromagnetic feld as previously shownby Chater et al. [45]. By contrast, Amara et al. [50] showedanincreaseinMDAlevel inliverandkidney, indicatingoxidative stress under SMF (128 mT, 1 h/day during 30 con-secutive days).Tis discrepancy may be explained by theintensity and the duration of the exposure. Te cellular andmolecular modifcations 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 efect ofselenium (Se) supplementation in SMF-exposed rats.Pre-treatment with Se (Na2SeO3,0.2 mg/L,for 30 consecutivedays, per os) preventedplasma -tocopherol andretinoldecrease induced by SMF exposure.Amara et al. [50] examined the efect of zinc supplemen-tation on the antioxidant enzymatic system, lipid peroxida-tion and DNA oxidation in SMF-exposed rats. Te exposureof rats to SMF (128 mT, 1 h/day during 30 consecutive days)decreasedtheactivitiesof GPx, CAT, andSODactivitiesand increased MDA concentration in liver and kidneys. Zincsupplementation (ZnCl2, 40 mg/L, per os) in SMF-exposedrats 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. Te authors suggested that zinc supplementationminimizes oxidative damage induced by SMF in rat tissues.Te 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. Te SMF increases the concentration and/or 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].ExposuretoSMF(128 mT, 1 h/day, during5consecu-tivedays) inducedsympatheticneurons systemhyperac-tivity associated with hypoxia-like status [52] and elevatedplasmacorticosteroneandmetallothioneinconcentrationsand 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 defciency in tissues [43, 44, 46, 50]. Agayet al. [55] have demonstrated that alteration of antioxidanttraceelements(Zn, Se, andCu)disruptstheactivitiesofantioxidant enzymes. Dudaet al. [56]reportedachangeinliverand kidneysconcentration ofcopper, manganese,cobalt and iron in rats exposed to static and low-frequencymagneticfelds. SMFprobablyinduces aconformationalchangeofantioxidantenzymesthatleadstolossoftheircatalytic activity [56].A few studies concerning the supplemental antioxidantsvitamins Cand E have focused on the preventive and curativeproperties in damage induced by SMF exposure [57]. Jajteet al. [58] reported the efect of melatonin and vitamin Eon the level of lipid peroxidation in rat blood lymphocytesexposed to iron ions and/or SMF. When cells were treatedwith melatonin or vitamin E and then exposed to iron ionsandSMF, thelevel oflipidperoxidationwassignifcantlyreduced.Sullivanet al. [59] reportedthat SMF(230250 mT)exposure stimulates ROS productioninhumanfetal lung cells(WI-38) during the frst 18 h period when cells are attachingto the culture vessel. Tese results support the hypothesisthat increased ROS formation may account for SMF efectson cell attachment. However, SMF decreases growth in cellwhen the increase in ROS was abated, suggesting that othermechanisms account for SMF efects on cell growth.Kabuto et al. [60] showed that an SMF (5300 mT for40 min)hadnoefectontheaccumulationofTBARSinmousebrainhomogenatesinducedbyFeCl3. Incontrast,whenthehomogenateswereincubatedwithFeCl3inanSMF (24 mT), the accumulation of TBARS was decreased.Te accumulation of TBARS in phosphatidylcholine solution4 BioMed Research InternationalincubatedwithFeCl3andH2O2 was alsoinhibitedby the SMFexposure. Tese results suggest that the SMF could have aninhibitory efect on Fe2+-induced lipid peroxidation, and theefectiveness of this SMF suppression on Fe2+-induced ROSgeneration is restricted to a window of feld intensity of 2 to4 mT.Currently, environmental and industrial pollution causesmultiple stress conditions; the combined exposure to mag-netic feld and other toxic agents is recognized as an impor-tant research area, with a view to better protecting humanhealthagainst their probable unfavorable efects. Amaraet al. [61] investigated the efect of coexposure to SMF andcadmium(Cd) ontheantioxidant enzymes activityandMDAconcentrationinrat skeletal andcardiac muscles.Teexposureof rats toSMF(128 mT, 1 h/dayduring30consecutive days) decreased the activities of GPx and CuZn-SOD in heart muscle. Exposure to SMF increased the MDAconcentrationinratcardiacmuscle. Tecombinedefectof SMF and Cd (CdCl2,40 mg/L,per os) disrupted morethe antioxidant enzymes activity in rat skeletal and cardiacmuscles.Te combined efect of SMF (128 mT, 1 hour/day for 30consecutivedays)andCdCl2(40 mg/L, peros)decreasedSODactivity andglutathione level andincreasedMDAconcentrationinfrontal cortex as comparedwithCd-exposedrats [62].In pregnant rats coexposed to cadmium (CdCl2,3.0 mg/Kgbodyweight)andSMF(128 mT/1 h/day)for13consecutive days as from the 6th to 19th day of gestation,no efects on activities of antioxidant were observed in bothtissues compared to cadmium-treated group [63]. However,the associationbetweenSMFandCddecreasedplasmaMDA concentration, suggesting that a homeostatic defensemechanism was activated when SMF was associated to Cd inpregnant rats.2.2. Strong and Ultrastrong Static Magnetic Fields and Oxida-tive Stress. Although strong SMF is supposed to have thepotential to afect biological systems, the efects have not beenevaluated sufciently.Sirmatel etal. [64]investigatedtheefectsof ahigh-strength magnetic feld produced by an MRI apparatus onoxidativestress. Teefectsof SMF(1.50 T) onthetotalantioxidant capacity (TAC), total oxidant status (TOS), andoxidativestressindex(OSI)inmalesubjectswereinves-tigated. In this study, 33 male volunteers were exposed toSMFfor ashort time, andthe TAC, TOS, andOSI ofeachsubjectweredeterminedusingthemethodsofErel.Magneticfeldexposurewas providedusingamagneticresonance apparatus; radiofrequency was not applied. TACshowed a signifcant increase in postexposures compared topreexposures to the magnetic feld ( < 0.05). OSI and TOSshowed a signifcant decrease in postexposures compared topreexposures to SMF (for each of two, < 0.01). Te 1.50 TSMF used in the MRI apparatus did not yield a negative efect;on the contrary, it produced the positive efect of decreasingoxidative stress in men following short-term exposure.TeNakagawaresearchgroup[65, 66]measuredandevaluated a ROS scavenger,metallothionein (MT),a ROSproduct, and lipid peroxidation in the liver, kidneys, heart,lung, and brain of 8-week-old male BALB/c mice in vivo. Temice were exposed to an SMF of 3.0 and 4.70 T for 148 h. A4.70 T SMF exposure for 648 h increased both MT and lipidperoxidation levels in the liver alone. A 3.0 T SMF exposurefor 148 h did not induce any changes in both MT and lipidperoxidation levels in all the tissues. A single subcutaneousinjection of CCl4 (0.5 mL/kg) increased both MT and lipidperoxidationlevels intheliver, andthecombinationofCCl4 administration and a 4.70 T SMF for 24 h potentiatedbothMTandlipidperoxidationlevels. Te increase inactivities of both glutamic-oxaloacetic transaminase (GOT)and glutamic-pyruvic transaminase (GPT) caused by CCl4administration 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 CCl4 injection.3. Genotoxicity, DNA Damage, and ApoptosisHealth and environmental concerns have been raised becausethe SMF efects on oxidative stress leading to genetic muta-tion and apoptosis/necrosis have been found. It seems to takeplace from free radical generation.Several experiments have beenshown, and they discussedhow SMF can infuence 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 afect cells by dam-aging macromolecules, such as DNA, protein, and membranelipids. Several reports have indicated that SMF enhances freeradical activity in cells [6771], particularly via the Fentonreaction [70]. Te Fenton reaction is a process catalyzed byironinwhichhydrogenperoxide, aproduct of oxidativerespiration in the mitochondria, is converted into hydroxylfree radicals, which are very potent and cytotoxic molecules.3.1.Genotoxic Efects of Moderate-Intensity Static MagneticFields. Amaraet al. [44] investigatedthe efect of SMFexposure in DNA damage in THP1 cells (monocyte line).Cell culture fasks were exposed to SMF (250 mT) during1 h, 2 h, and 3 h. Te results showed that cell viability wasslightly lower in SMF-exposed groups compared to a sham-exposedgroup. DNAanalysis 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 afer 3 h of exposition.To further explore the oxidative DNA damage, cellular DNAwas isolated,hydrolyzed,and analyzed by HPLC-EC.Televel of 8-oxo-7,8-dihydro-2

-deoxyguanosine (8-oxodGuo)remained unchanged compared to the sham-exposed group(+6.5%, > 0.05). Te results showed that SMF exposure(250 mT, during 3 h) did not cause oxidative stress and DNAdamage in THP1 cells.Exposure of rats toSMF(128 mT, 1 h/dayduring30consecutive 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 oxidativeBioMed Research International 5damage [43]. Te same treatment elevated the 8-oxodGuoin kidneys but not in liver. Zinc supplementation (ZnCl2,40 mg/L, per os) attenuated DNA oxidation induced by SMFin kidneys to the control level [50].Simultaneousexposureof rat lymphocytestoa7 mTSMF and ferrous chloride (FeCl2) caused an increase in thenumber of cells with DNAdamage [72, 73]. No signifcant dif-ferences were observed between unexposed lymphocytes andlymphocytes exposed to a 7 mT SMF or FeCl2 (10 mg/mL).However, when lymphocytes were exposed to a 7 mT staticmagnetic feld and simultaneously treated with FeCl2, therewas a signifcant increase in the percentage of apoptotic andnecrotic cells accompanied by signifcant alterations in cellviability.However, anincreasingnumberof evidenceindicatesthat SMFs are capable of altering apoptosis, mainly throughmodulationof Ca2+infux. Tenuzzoet al. [74] observedthat exposure to a 6-mT SMF afects the apoptotic rate inisolated human lymphocytes, the expression and distributionof pro- and antiapoptotic genes, and the concentration ofintracellular Ca2+. Tey also suggest that modulation of theapoptotic rate is not a consequence of the direct physicalinteraction between the feld and the apoptotic inducers butthe fnal result of multiple perturbations of Ca2+-regulatedactivity and gene-related transcription factors and membranecomponents, which collectively afect the apoptotic response.SMFs above 600 mT were found to decrease the extent ofcell death by apoptosis induced by several agents in diferenthuman cell systems of U937 and CEM cells in an intensity-dependent fashion, reachingaplateauat 6 mT[75]. Teprotective efect was found to be mediated by the ability of thefelds to enhance Ca2+ infux from the extracellular medium;accordingly, it was limited to those cell systems where Ca2+infux was shown to have an antiapoptotic efect. In additionto the SMF-enhancing efect 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 efects of SMFson the cellular immune parameters of the C57BI/6 murinemacrophages, spleen lymphocytes, and thymic cells. Te cellswereexposedinvitrofor24 hat 37C, 5%CO2, to25150 mT SMF. Exposure to the SMF resulted in the decreasedphagocytic uptake of fuorescent latex microspheres, whichwasaccompaniedbyanincreasedintracellularCa2+levelinmacrophages. Exposure toSMFdecreasedmitogenicresponses in lymphocytes, as determined by incorporationof [3H] thymidine into the cells. Tis was associated withthe increased Ca2+ infux in concanavalin A-stimulated lym-phocytes. Furthermore, exposure to SMF produced markedlyincreased apoptosis of thymic cells, as determined by fowcytometry. Overall, in vitro exposure of immunocompetentcells to 25150 mT SMF altered several functional parametersof C57BI/6murinemacrophages, thymocytes, andspleenlymphocytes [77].Apoptosis induced by magnetic feld in female rats wasinvestigatedby using the Tdt mediateddUTPnick-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. Tedensityoftheapoptoticcellswassignifcantincortical zone, thaninthemedullarzone. Bycontrast,nolabelingwas foundinliver andkidneys followingSMF-exposure. Tus, it maybeconcludedthat SMFinducedapoptosis inthymic cell death but not inthe liver and kidneys.Although the mechanisms by which SMF initiates apoptosisin thymocytes are presently not known, and reactive oxygenspecies are likely to play a role.Ishisakaetal. [78]investigatedtheefectsofanSMF(25 mT for 1 h) on the apoptosis of human leukemic cell line(HL-60) induced by exogenous H2O2. Te H2O2 induced arapid DNA fragmentation and a slow decrease in viability ofHL-60 cells. However, the SMF itself (6 mT for 18 h) did notexert any efect on the H2O2-induced DNA fragmentation orviability.HL-60 cells were exposed to SMF of 6 mTwith or withoutDNA topoisomerase I inhibitor, camptothecin for 5 h. SMFalone did not produce any apoptogenic or neurogenic efectin HL-60 cells [79]. SMFs alone or in combination with cam-ptothecin did not afect overall cell viability, but they accel-erated the rate of cell transition from apoptosis to secondarynecrosis afer induction of apoptosis by camptothecin.In addition, Teodori et al. [80, 81] reported that a uniformSMF(6 mTfor18 h; 8and30 mTfor3 h)didnot afectviability of human glioblastoma cells. However, a uniformSMF of 300 mT for 3 h increased apoptosis. Te interferenceof the SMF (6 mT for 18 h) with physical(heat shock) orchemical (etoposide, VP16) induced apoptosis may be relatedto oxidative stress.Potenza et al. [82] describedthe efects of SMFoncell growthandDNAintegrityof humanumbilical veinendothelial cells (HUVECs). Te authors investigated thata 4 h exposure of HUVECs to SMFs of moderate intensity(300 mT) induced a transient DNA damage both at the nu-clear and mitochondrial levels. Tis response was par-alleledby increased mitochondrial DNA content and mitochondrialactivity and by a higher expression of some genes related tomitochondrial biogenesis 24 h afer SMF exposure.Hao et al. [83] investigated whether SMFs (8.8 mT, for12 h) can enhance the killing efect of adriamycin (ADM)in human leukemia cells (K562). Te 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 efect.Sarvestani et al. [84] evaluated the infuence of an SMF(15 mT, for 5 h) on the progression of cell cycle in rat BMSCs.Tecellsweredividedintotwogroups. Onegroupwasexposed to SMF alone, whereas the other group was exposedto X-rays before SMF exposure. Te population of cells didnot show any signifcant diference in the frst group,butthesecondgroupexposedtoacuteradiationbeforeSMFexposure showed a signifcant increase in the number of cellsin the G2/M phase. Te SMF intensifed the efects of X-rayexposure, whereas SMF alone did not have any detectableinfuence on cell cycle.6 BioMed Research International3.2. Genotoxic Efects of Strong and Ultrastrong Static MagneticFields. It is generally accepted that static felds below 1 T arenot genotoxic [32, 33, 85]. However, a recent study by Suzukiet al. [86] reported a signifcant, time- and dose-dependentincrease in micronucleus frequency in mice exposed to staticmagnetic felds of 2,3,or 4.7 T for 24,48,or 72 h,usinga standard micronucleus assay. Bone marrow smears weretakenimmediatelyafer exposure, andthe frequencyofmicronucleated polychromatic (immature) erythrocytes wasscored. Micronucleus frequency was signifcantly increasedfollowing exposure to 4.7 T for all three time periods and to3 T afer exposure for 48 or 72 h, whereas exposure to 2 Thad no signifcant efect. Te authors suggest that exposure tohigher felds may have induced a stress reaction or directlyafectedchromosomestructureor separationduringcelldivision.Te clinical and preclinical uses of high-feld intensity(HF, 3 Tandabove) magneticresonanceimaging(MRI)scanners have signifcantly increased in the past few years.However, potential health risks are implied in the MRI andespecially HF MRI environment due to high-static magneticfelds, fast gradient magneticfelds, andstrongradiofre-quencyelectromagneticfelds. Tegenotoxicpotential 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 electromagneticfelds generated during MRI scanning (clinical routine brainexamination protocols: three-channel head coil) for 22, 45,67, and 89 min. A signifcant 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 manner.Te frequencies of MN in lymphocytes exposed to complexelectromagneticfeldsfor0, 22, 45, 67, and89 minwere9.67, 11.67, 14.67, 18.00, and 20.33 per 1000 cells, respectively.Similarly, the frequencies of CAs in lymphocytes exposed for0, 45, 67, and 89 min were 1.33, 2.33, 3.67, and 4.67 per 200cells, respectively. Tese results suggest that exposure to 3 TMRI induces genotoxic efects in human lymphocytes.Schreiber et al. [88] reported no mutagenic and comuta-genic efects of magnetic felds used for MRI.Schwenzer et al. [89] evaluated the efects of the staticmagneticfeldandtypical imagingsequencesof ahigh-feld magnetic resonance scanner (3 T) on the induction ofdouble strandbreaks (DSBs) intwo diferent humancell lines.Human promyelocytic leukemia cells (HL-60) and humanacute myeloid leukemia cells (KG-1a) were exposed to theSMFaloneandtoturbospin-echo(TSE) andgradient-echo(GE)sequences. Flowcytometrywasusedtoquan-tify gammaH2AX expression of antibody-stained cells as amarkerfordeoxyribonucleicacidDSBsonehourand24hours afer magnetic feld exposure. X-ray-treated cells wereused as positive control. Neither exposure to the SMF alonenortotheappliedimagingsequencesshowedsignifcantdiferences in gammaH2AXexpression between exposed andsham-exposed cells.X-ray-treated cells as positive controlshowed a signifcant increase in gammaH2AX expression.SMF alone and MRI sequences at 3 T have no efect on theinduction of DSBs in HL-60 and KG-1a cells.Te efects of SMF (4.70 T) on the frequency of micronu-cleatedcells inCHL/IUcells inducedby mitomycinC(MMC) were studied in vitro [90]. Te 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 signifcantlydecreased the frequency of MMC-induced micronucleatedcell expression afer culture periods of 18, 42, 54, and 66 h.Tese results suggested that SMF (4.70 T) might have exertedan infuence 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 efect of 3 or 5 T SMFongeneexpressionintheexperimental model metazoanCaenorhabditis elegans. In addition, transient induction ofhps12 family genes was observed afer SMF exposure. Tesmall-hps gene, hps16, was alsoinducedbut toamuchlesser extent, and the lacZ-stained population of hps16-1::lacZtransgenic worms did not signifcantly increase afer SMFexposure with or without a second stressor, mild heat shock.Several genes encoding apoptotic cell death activators andsecretedsurfaceproteins wereupregulatedafer ionizingradiation (IR), but they were not induced by SMF. Te RT-PCR analyses for 12 of these genes confrmed the expres-sion diferences between worms exposed to SMF and thoseexposedto IR. Incontrast to IR, exposure to high SMFsdidnot induceDNAdouble-strandbreaks or germlinecell apoptosis during meiosis. Tese results suggest that theresponse of C. elegans to high SMFs is unique and capable ofadjustment during long exposure and that this treatment maybe less hazardous than other invasive treatments and drugs.Koanaetal. [92]examinedthegenotoxicefectsofa5 T SMF for 24 h in a DNA-repair defective mutant of D.melanogaster using the somatic mutation and recombinationtest (SMART) [93] because this test was useful to detect themutagenic activity of SMF and EMF. Tey reported that theSMF exposure increased the frequency of mutation in mei-41heterozygotes and that the increase was suppressed to controllevels by supplementation with vitamin E, which is a lipid-soluble antioxidant and a nonspecifc radical scavenger.An Escherichia coli (E. coli) mutation assay was used toassess the mutagenic efects of strong static magnetic felds[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. Te expression of the soxS::lacZfusion gene was assessed by measuring b-galactosidase activ-ity. Te results for survival or mutation obtained with thewild-type E. coli strain GC4468 and its derivatives defectivein DNArepair enzymes or redox-regulating enzymes showednoefect of exposure. Ontheotherhand, themutationfrequency was signifcantly increased by exposure to SMF of9 T in soxR and sodAsodB mutants, which are defective indefense mechanisms against oxidative stress.Ikehataet al. [94] examinedpossiblemutagenicandcomutagenicefectsof strongstaticmagneticfeldsusingthe bacterial mutagenicity test. No mutagenic efect of SMFsupto5 Twas detectedusingfour strains of SalmonellaBioMed Research International 7typhimuriumandE. coli WP2uvrA. Te mutationratein the exposed group was signifcantly higher than inthenonexposedgroupwhencells weretreatedwithN-ethyl-N0-nitro-N-nitrosoguanidine, N-methyl-N0-nitro-N-nitrosoguanidine, ethylmethanesulfonate, 4-nitroquinoline-N-oxide, 2-amino-3-methyl-3H-imidazo[4,5-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 afect cell growth rate or cell cycle distribution in Chinesehamster ovary CHO-K1 cells [95]. Exposure to SMF alonedid not afect micronucleus formation. In X-ray irradiatedcells, exposure to a 1 T SMF also did not afect micronucleusformation, but exposure to a 10 TSMF resulted ina signifcantincreaseinmicronucleusformationinducedafera4 Gyexposure. One of the mechanisms of this efect is attributableto the 10 T SMF-induced oxidative DNA damage.4. Cancer StudiesMany researchers have observed the efects of SMFs on tumorcells, particularly the inhibiting efects. Tey have used SMFas an entry point for investigating biological efects. In ordertoreducethetoxicityandresistanceof singleanticancerdrugs, avarietyofunifedtreatmentswererequired. Tesynergy of magnetic felds and anticancer drugs was one ofthe methods that provides a new strategy for the efectivetreatment of cancer.4.1. Moderate-IntensityStaticMagneticFields andCancer.Gray et al. [71] evaluated the efects of non-uniform 110 mTSMF for four 4 h periods, with 812 h between each exposure,anddoxorubicin(10 mg/kg, i.p.)onfemaleB6C3F1 micewith transplanted mammary adenocarcinoma. Teir resultsrevealedthatthegroupsexposedtoSMFcombinedwithdoxorubicin achieved signifcantly greater tumor regressionthanthe grouptreatedwithadriamycin(ADM) alone. Inaninvivo experiment, mice bearing murine Lewis lung carcinomas(LLCs) weretreatedwith3 mTSMFfor 35 min/dayandcisplatin(3 mg/kg, i.p.) [96]. Te survival time of micetreated with cisplatin and SMF was signifcantly longer thanthat of mice treated only with cisplatin or SMF exposure.Tese results show that SMF can inhibit the proliferation ofcancer cells, and the killing efects of SMF combined withantineoplastic drugs on cancer cells are greater than those ofSMFs or anticancer drugs alone. Tese observations suggest apotential strategy for chemotherapy, that is, the combinationtherapyof SMFs andchemotherapeuticdrugs. However,so far it remains unclear which mechanism underlies thekilling efects of SMFs combined with chemotherapy drugson cancer cells.Sun et al. [97] evaluated the ability of 8.8 mT SMFs toenhancetheinvitroactionof achemotherapeuticagent,paclitaxel, against K562 human leukemia cells. Te authorsanalyzed the cell proliferation, cell cycle distribution, DNAdamage, andalterationof cell surfaceandcell organelleultrastructureaferK562cellswereexposedtopaclitaxelinthe presence or absence of SMF. the results showedthat, in the presence of SMF, the efcient concentration ofpaclitaxel on K562 cells was decreased from 50 to 10 ng/mL.Cell cycleanalysisindicatedthat K562cellstreatedwithSMF plus paclitaxel were arrested at the G2 phase, whichwas mainly induced by paclitaxel. Trough comet assay, theauthors found that the cell cycle arrest efect of paclitaxelwith or without SMF on K562 cells was correlated with DNAdamage. Te 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 augmented.Te authors indicated that the potency of the combination ofSMF and paclitaxel was greater than that of SMF or paclitaxelalone on K562 cells, and these efects were correlated withDNAdamageinducedbySMFandpaclitaxel. Terefore,thealteration ofcell membrane permeabilitymaybeoneimportantmechanismunderlyingtheefectsof SMFandpaclitaxel on K562 cells.Strieth et al. [98] analyzed the efects of SMF (587 mT)on tumor microcirculation. In vivo fuorescence microscopywas performed in A-Mel-3 tumors growing in dorsal skinfoldchamber preparations of hamsters. Short time exposuretoSMF(150 mT) resultedinasignifcant reductionofcapillaryredbloodcellsvelocities(vRBC)andsegmentalblood fow in tumor microvessels. At the maximum strengthof 587 mT, areversiblereductionof vRBC(40%)andoffunctional 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 remainedunafectedbySMFexposures.However, in contrast to tumor-free striated muscle controls,exposure at the maximum fux density of 587 mT induced asignifcant increase in platelet-endothelial cell adherence ina time-dependent manner that was reversible afer reducingthestrengthoftheSMF. Teauthorsassumedthatthesereversible changes may have implications for functionalmeasurements of tumor microcirculation by MRI and newtherapeutic strategies using strong SMFs. Te same researchgroupfurther evaluatedthe efects of anSMF(586 mT, for 3 h)on tumor angiogenesis and growth [99]. Analysis of micro-circulatoryparametersrevealedasignifcant reductionofFVD, vessel diameters, and RBCvelocity in tumors afer SMFexposure compared with the control tumors. Tese changesrefect retarded vessel maturation by antiangiogenesis. Teincreased edema afer SMF-exposure indicated an increasedtumor microvessel leakiness possibly enhancing drug uptake.Te authors concluded that SMF therapy appears to be apromising new anticancer strategy, as an inhibitor of tumorgrowthandangiogenesisandasapotential sensitizertochemotherapy.Chen et al. [100] investigated whether 8.8 mT SMFs canenhance the killing potency of cisplatin (DDP) on humanleukemic cells (K562). Te results show that SMFs enhancedthe anticancer efect of DDP on K562 cells. Te mechanismcorrelatedwiththeDNAdamagemodel. Tisstudyalsoshows the potentiality of SMFs as an adjunctive treatmentmethod for chemotherapy.Hao et al. [83] investigated whether a moderate-intensitySMF can enhance the killing efect of ADM on K562 cells8 BioMed Research Internationalandexploretheefectsof SMFcombinedwithADMonK562 cells. Te authors analyzed the metabolic activity ofcells, cell cycledistribution, DNAdamage, changeincellultrastructure, andP-glycoprotein(P-gp) expressionaferK562 cells were exposed continuously to a uniform 8.8 mTSMF for 12 h, with or without ADM. Teir results showedthat the SMF combined with ADM (25 ng/mL) signifcantlyinhibited the metabolic activity of K562 cells, while neitherADM nor the SMF alone afected the metabolic activity ofthese cells. Cell ultrastructure was altered in the SMF +ADMgroup. Forexample, cell membranewasdepressed, someprotuberances wereobservable, and vacuolesinthe cyto-plasm became larger. Cells were arrested at the G2/M phaseandDNAdamageincreasedafercellsweretreatedwiththe 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 group.Taken together, these results showed that the 8.8 mT SMFenhanced the cytotoxicity potency of ADMonK562 cells, andthe decrease inP-gpexpressionmay be one reasonunderlyingthis efect.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). Te drugs were taxol (alkaloid), doxorubicin(anthra-cycline), cisplatin(platinumcompound), andcyclophos-phamide(alkylatingagent). Holeswereobservedincellsexposed to SMF but not in control groups. Te number, size,and shape of the holes were dependent on the drug type,SMF parameters, and the duration of exposure. Te resultssuggest that the application of a SMF could alter membranepermeability, increasing the fowof the anticancer drugs. Tismay be one of the reasons why SMF can strength then theefect of anticancer drugs. Observations were also made ofthe efect of using diferent anticancer drugs. For example,the efect of SMF combined with taxol or cyclophosphamideon the cells was additive while the efect of SMF combinedwith cisplatin or doxorubicin was synergistic. Te target sitesof cisplatinanddoxorubicinarenucleicacids; continousresearch is required into this important area to ascertain theefect of SMF on nucleic acids.4.2. Strong and Ultrastrong Static Magnetic Fields and Cancer.Recently, some studies have suggested that SMFs have thepotential as an adjunctive treatment method for chemother-apy, sinceSMFs infuencecell growth, proliferation, andstructureof cancer cells [98, 99, 102107]. Inparticular,thekillingefect of antineoplasticdrugs oncancer 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 an NMRapparatus can afectapoptosisinducedonreportertumorcellsofhematopoi-eticorigin. Teimpressiveresultwasthestrongincrease(by 1.82.5-fold) of damage-induced apoptosis by NMR. Tispotentiationis duetocytosolicCa2+overloadtoNMR-promoted Ca2+ infux, 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-termcell survival, thus increasingthe efciencyofcytocidal treatments. Mononuclear white blood cells are notsensitized to apoptosis by NMR,showing that NMR mayincrease the diferential cytotoxicity of antitumor drugs ontumor versus normal cells. Te authors suggested that thisstrong, diferential potentiatingefect of NMRontumorcell apoptosis may have important implications, as in fact apossible adjuvant for antitumor therapies.5. Summary and ConclusionsInrecentyears, anabundanceofresearchpapers, reviewpapers, and books has been published describing the possiblephysical and biological interactions of magnetic felds.Considering these articles comprehensively, the con-clusionsareasfollows: theprimarycauseof changesincells afer incubation in external SMF is disruption of freeradical metabolismand elevationof their concentration. Suchdisruption causes oxidative stress and, as a result, damagesionchannels, leadingtochangesincell morphologyandexpression of diferent 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 efects 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 stronglysuggestingthat anSMFmodifes their efects. Efects ofSMFs on apoptosis are a potentially interesting phenomenon.However,these efects ofen depended on a cell type andwere not found in various types of cells. Many researchershave observed the efects of SMFs on tumor cells, particularlytheinhibitingefects. Inordertoreducethetoxicityandresistanceof singleanticancerdrugs, avarietyof unifedtreatments were required. Te synergy of magnetic felds andanticancer drugs was one of the methods. It provides a newstrategy for the efective treatment of cancer.Tese studies provide valuable insight intothe 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, Static magnetic felds: animal studies, Progress inBiophysics and Molecular Biology, vol. 87, no. 2-3, pp. 225239,2005.[2]M. S. Markov, Biological windows: a tribute to W. Ross Adey,Environmentalist, vol. 25, no. 24, pp. 6774, 2005.[3]W. R. Adey, Models of membranes of cerebral cells as substratesfor information storage, BioSystems, vol. 8, no. 4, pp. 163178,1977.BioMed Research International 9[4]W.R.Adey,Te sequence and energetic of cell membranecoupling to intracellular enzyme systems, Bioelectrochemistryand Bioenergetics, vol. 15, no. 3, pp. 447456, 1986.[5]M. S. Markov, Electromagnetic feld infuence on membranes,in Interfacial Phenomena in Biological System, M. Bender, Ed.,pp. 171192, Marcel Dekker, 1991.[6]WorldHealthOrganization, Static Fields, EnvironmentalHealth Criteria, 232, Geneva, Switzerland, 2006.[7]A. P. Colbert, J. Souder, andM. Markov, Staticmagneticfeld therapy: methodological challenges to conducting clinicaltrials, Environmentalist, vol. 29, no. 2, pp. 177185, 2009.[8]A. H. Hashish, M. A. El-Missiry, H. I. Abdelkader, and R. H.Abou-Saleh, Assessment of biological changes of continuouswhole body exposure to static magnetic feld and extremely lowfrequency electromagnetic felds in mice, Ecotoxicology andEnvironmental Safety, vol. 71, no. 3, pp. 895902, 2008.[9]M. J. McLean, R. R. Holcomb, A. W. Wamil, J. D. Pickett, and A.V. Cavopol, Blockade of sensory neuron action potentials bya static magnetic feld in the 10 mT range, Bioelectromagnetics,vol. 16, no. 1, pp. 2032, 1995.[10]M. S. Markov, Terapeutic applicationof static magneticfelds, Environmentalist, vol. 27, no. 4, pp. 457463, 2007.[11]H. Sahebjamei, P. Abdolmaleki, and F. Ghanati, Efects of mag-netic feld on the antioxidant enzyme activities of suspension-cultured tobacco cells, Bioelectromagnetics, vol. 28, no. 1, pp.4247, 2007.[12]G. Zhao, S. Chen, L. Wanget al., Cellular ATPcontentwas decreased by a homogeneous 8.5 T static magnetic feldexposure: role of reactive oxygen species, Bioelectromagnetics,vol. 32, no. 2, pp. 94101, 2011.[13]S. Ueno and T. Shigemitsu, Biological efects of static magneticfelds,inHandbookof Biological Efects of ElectromagneticFields: Bioengineering and Biophysical Aspects of ElectromagneticFields, F. S. Barnes and B. Greenebaum, Eds., CRC Press, BocaRaton, Fla, USA, 3rd edition, 2007.[14]S. Ueno and K. Harada, Experimental difculties in observingthe efects of magnetic felds onbiological andchemicalprocesses, IEEE Transactions on Magnetics, vol. 22, no. 5, pp.868873, 1986.[15]K. A. McLauchlan and U. E. Steiner, Te spin correlated radicalpair as a reaction intermediate, Molecular Physics, vol. 73, no.2, pp. 241263, 1991.[16]J. R. Connor and S. L. Menzies, Cellular management of ironinthebrain,Journal of theNeurological Sciences, vol. 134,supplement, pp. 3344, 1995.[17]W. R. Markesbery, Oxidative stress hypothesis in Alzheimersdisease, Free Radical Biology and Medicine, vol. 23, no. 1, pp.134147, 1997.[18]W. H. Koppenol, Te Haber-Weiss cycle70 years later, RedoxReport, vol. 6, no. 4, pp. 229234, 2001.[19]International Commission on Non-Ionizing Radiation Protec-tion(ICNIRP), Guidelines onlimits of exposuretostaticmagnetic felds, Health Physics, vol. 96, no. 4, pp. 504514, 2009.[20]N.Mohtat,F.L.Cozens,T.Hancock-Chen,J.C.Scaiano,J.McLean, and J. Kim, Magnetic feld efects on the behaviorof radicals in protein and DNA environments, Photochemistryand Photobiology, vol. 67, no. 1, pp. 111118, 1998.[21]Q.M.Zhang,M.Tokiwa,T.Doi et al.,Strong static mag-netic feld and the induction of mutations through elevatedproduction of reactive oxygen species in Escherichia coli soxR,International Journal of Radiation Biology, vol. 79, no. 4, pp. 281286, 2003.[22]H. Okano, Efects of static magnetic felds in biology: role offree radicals, Frontiers in Bioscience, vol. 13, no. 16, pp. 61066125, 2008.[23]L. Dini, Phagocytosis of dying cells: infuence of smoking andstatic magnetic felds, Apoptosis, vol. 15, no. 9, pp. 11471164,2010.[24]J. Miyakoshi, Efects of static magnetic felds at the cellularlevel, Progress in Biophysics and Molecular Biology, vol. 87, no.2-3, pp. 213223, 2005.[25]AGNIR,ELF electromagnetic felds and the risk of cancer.Report of anAdvisoryGrouponNon-IonisingRadiation,Documents of the NRPB, vol. 12, no. 1, 2001.[26]WHO, Magnetic Fields, Environmental Health Criteria 69,World Health Organisation, Geneva, Switzerland, 1987.[27]C. I. Kowalczuk, Z. J. Sienkiewicz, and R. D. Saunders, Biolog-ical efects of exposure to non-ionising electromagnetic feldsand radiation. I. Static electric and magnetic felds, Tech. Rep.NRPB-R238, NRPB, Chilton, Wis, USA, 1991.[28]ICNIRP, Guidelines on limits of exposure to static magneticfelds, Health Physics, vol. 66, no. 1, pp. 100106, 1994.[29]ICNIRP, Biological efects of static andELFelectric andmagneticfelds,in ProceedingsoftheInternational Seminaron Biological Efects of Static and ELF Electric and MagneticFields and Related Health Risks, Bologna, Italy (ICNIRP 97),R. Matthes, J. H. Bernhardt, and M. H. Repacholi, Eds., vol. 4,M arkl-Druck, M unchen, Germany, 1997.[30]M. H. Repacholi and B. Greenebaum, Interaction of static andextremely lowfrequency electric and magnetic felds with livingsystems: health efects and research needs, Bioelectromagnetics,vol. 20, no. 3, pp. 133160, 1999.[31]International Agency for Research on Cancer (IARC), IARCMonographs on the Evaluation of Carcinogenic Risks to Humans.Non-Ionising Radiation. Part 1: Static and Extremely Low Fre-quency (ELF) Electric and Magnetic Fields, vol. 80, IARC, Lyon,France, 2002.[32]ICNIRP,Exposure to static and low frequency electromag-netic felds, inBiological Efects andHealthConsequences(0100 kHz) (ICNIRP 03), R. Matthes, A. F. McKinlay, J. H.Bernhardt, P. Vecchia, and B. Veyret, Eds., vol. 13, M arkl-Druck,M unchen, Germany, 2003.[33]A. F. McKinlay, S. G. Allen, R. Cox et al., Reviewof the scientifcevidence for limiting exposure to electromagnetic felds (0300GHz), Documents of the NRPB, vol. 15, no. 3, 2004.[34]L. Dini and L. Abbro, Bioefects of moderate-intensity staticmagnetic felds on cell cultures, Micron, vol. 36, no. 3, pp. 195217, 2005.[35]J. L. Phillips, N. P. Singh, and H. Lai, Electromagnetic felds andDNAdamage, Pathophysiology, vol. 16, no. 2-3, pp. 7988, 2009.[36]S. UenoandH. Okano, Static, low-frequency, andpulsedmagnetic felds in biological systems, in Electromagnetic Fieldsin Biological Systems, chapter 3, pp. 115196, Taylor & FrancisGroup, LLC, 2012.[37]S. Engstr om, Magnetic feld efects on free radical reactionsin biology, in Handbook of Biological Efects of ElectromagneticFields: Bioengineering and Biophysical Aspects of ElectromagneticFields, F. S. Barnes and B. Greenebaum, Eds., CRC Press, BocaRaton, Fla, USA, 3rd edition, 2007.[38]C. Nathan, Nitric oxide as a secretory product of mammaliancells, Te FASEB Journal, vol. 6, no. 12, pp. 30513064, 1992.[39]H. M. Lander, An essential role for free radicals and derivedspecies in signal transduction, Te FASEB Journal, vol. 11, no.2, pp. 118124, 1997.10 BioMed Research International[40]V. J. Tannickal and B. L. Fanburg, Reactive oxygen species incell signaling, American Journal of Physiology, vol. 279, no. 6,pp. L1005L1028, 2000.[41]B. Brocklehurst and K. A. McLauchlan, Free radical mecha-nism for the efects of environmental electromagnetic felds onbiological systems, International Journal of Radiation Biology,vol. 69, no. 1, pp. 324, 1996.[42]S. Amara, H. Abdelmelek, C. Garrel et al., Efects of subchronicexposure to static magnetic feld on testicular function in rats,Archives of Medical Research, vol. 37, no. 8, pp. 947952, 2006.[43]S. Amara, T. Douki, C. Garel et al., Efects of static magneticfeld exposure on antioxidative enzymes activity and DNA inrat brain, General Physiology and Biophysics, vol. 28, no. 3, pp.260265, 2009.[44]S. Amara, T. Douki, J. L. Ravanat et al., Infuence of a staticmagnetic feld (250 mT) on the antioxidant response and DNAintegrity in THP1 cells, Physics in Medicine and Biology, vol. 52,no. 4, pp. 889898, 2007.[45]S. Chater, H. Abdelmelek, T. Douki et al., Exposure to staticmagnetic feld of pregnant rats induces hepatic GSH elevationbut not oxidative DNA damage in liver and kidney, Archives ofMedical Research, vol. 37, no. 8, pp. 941946, 2006.[46]S. Ghodbane, S. Amara, C. Garrel et al., Selenium supplemen-tation ameliorates static magnetic feld-induced disorders inantioxidant status in rat tissues, Environmental Toxicology andPharmacology, vol. 31, no. 1, pp. 100106, 2011.[47]B. Kula, A. Sobczak, and R. Kuska, Efects of static and ELFmagnetic felds onfree-radical processes inrat liver and kidney,Electromagnetic Biology and Medicine, vol. 19, no. 1, pp. 99105,2000.[48]M. Zmyslony, J. Jajte, E. Rajkowska, and S. Szmigielski, Weak(5 MT) static magnetic feld stimulates lipid peroxidation in iso-latedrat liver microsomes invitro, Electro- and Magnetobiology,vol. 17, no. 2, pp. 109113, 1998.[49]S. Ghodbane, S. Amara, J. Arnaud et al., Efect of seleniumpre-treatment on plasma antioxidant vitamins A(retinol) and e(-tocopherol) in static magnetic feld-exposed rats, Toxicologyand Industrial Health, vol. 27, no. 10, pp. 949955, 2011.[50]S. Amara, H. Abdelmelek, C. Garrel et al., Zinc supplemen-tation ameliorates static magnetic feld-induced oxidative stressin rat tissues, Environmental Toxicology and Pharmacology, vol.23, no. 2, pp. 193197, 2007.[51]J. Walleczek and R. P. Liburdy, Nonthermal 60 Hz sinusoidalmagnetic-feld exposure enhances 45Ca2+ uptake in rat thymo-cytes: dependence onmitogenactivation, FEBS Letters, vol. 271,no. 1-2, pp. 157160, 1990.[52]H. Abdelmelek, A. Molnar, S. Servais et al., Skeletal muscleHSP72 and norepinephrine response to static magnetic feld inrat, Journal of Neural Transmission, vol. 113, no. 7, pp. 821827,2006.[53]S. Chater, H. Abdelmelek, D. Couton et al., Efects of sub-acuteexposure to magnetic feld on synthesis of plasma corticos-terone and liver metallothionein levels in female rats, PakistanJournal of Medical Sciences, vol. 20, no. 3, pp. 219223, 2004.[54]S. Chater, H. Abdelmelek, D. Couton, V. Joulin, M. Sakly, and K.Ben Rhouma, Sub-acute exposure to magnetic feld inducedapoptosis in thymus female rats, Pakistan Journal of MedicalSciences, vol. 21, no. 3, pp. 292297, 2005.[55]D. Agay, R. A. Anderson, C. Sandreet al., Alterations ofantioxidant trace elements (Zn, Se, Cu) and related metallo-enzymes in plasma and tissues following burn injury in rats,Burns, vol. 31, no. 3, pp. 366371, 2005.[56]D. Duda, J. Grzesik, and K. Pawlicki, Changes in liver andkidney concentrationof copper, manganese, cobalt andironratsexposed to static and low-frequency (50 Hz) magnetic felds,Journal of Trace Elements and Electrolytes in Health and Disease,vol. 5, no. 3, pp. 181186, 1991.[57]A. S. Monfared, S. G. Jorsaraei, and R. Abdi, Protective efectsof vitamins C and E on spermatogenesis of 1.5 tesla magneticfeld exposed rats, Journal of Magnetic Resonance Imaging, vol.30, no. 5, pp. 10471051, 2009.[58]J. Jajte, M. Zmyslony, and E. Rajkowska, Protective efect ofmelatonin and vitamin E against prooxidative action of ironions and static magnetic feld, Medycyna Pracy, vol. 54, no. 1,pp. 2328, 2003.[59]K. Sullivan, A. K. Balin, andR. G. Allen, Efectsof staticmagnetic felds on the growth of various types of human cells,Bioelectromagnetics, vol. 32, no. 2, pp. 140147, 2011.[60]H. Kabuto, I. Yokoi, N. Ogawa, A. Mori, and R. P. Liburdy,Efects of magnetic felds onthe accumulationof thiobarbituricacidreactive substances inducedby ironsalt andH2O2 inmousebrain homogenates or phosphotidylcholine, Pathophysiology,vol. 7, no. 4, pp. 283288, 2001.[61]S. Amara, C. Garrel, A. Favier, K. Ben Rhouma, M. Sakly, andH. Abdelmelek, Efect of static magnetic feld and/or cadmiumin the antioxidant enzymes activity in rat heart and skeletalmuscle, General Physiology and Biophysics, vol. 28, no. 4, pp.414419, 2009.[62]S. Amara, T. Douki, C. Garrel et al., Efects of static magneticfeld and cadmium on oxidative stress and DNA damage inrat cortex brain and hippocampus, Toxicology and IndustrialHealth, vol. 27, no. 2, pp. 99106, 2011.[63]S. Chater, T. Douki, A. Favier, C. Garrel, M. Sakly, andH.Abdelmelek, Infuence of static magnetic feld on cadmiumtoxicity: study of oxidative stress and DNA damage in pregnantrat tissues, Electromagnetic Biology and Medicine, vol. 27, no. 4,pp. 393401, 2008.[64]O. Sirmatel, C. Sert, F. Sirmatel, S. Selek, and B. Yokus, Totalantioxidant capacity, total oxidant status and oxidative stressindex in the men exposed to 1.5 T static magnetic feld, GeneralPhysiology and Biophysics, vol. 26, no. 2, pp. 8690, 2007.[65]M. Satoh, Y. Tsuji, Y. Watanabe et al., Metallothionein contentincreasedintheliverof miceexposedtomagneticfelds,Archives of Toxicology, vol. 70, no. 5, pp. 315318, 1996.[66]Y. Watanabe, M. Nakagawa, and Y. Miyakoshi, Enhancementof lipid peroxidation in the liver of mice exposed to magneticfelds, Industrial Health, vol. 35, no. 2, pp. 285290, 1997.[67]F. Cintolesi, T. Ritz, C. W. M. Kay, C. R. Timmel, and P. J. Hore,Anisotropic recombination of an immobilized photoinducedradical pair in a 50-T magnetic feld: a model avian photo-magnetoreceptor, Chemical Physics, vol. 294, no. 3, pp. 385399,2003.[68]O. EfmovaandP. J. Hore, Roleof exchangeanddipolarinteractions in the radical pair model of the avian magneticcompass, Biophysical Journal, vol. 94, no. 5, pp. 15651574, 2008.[69]R. W. Kay, Geomagnetic storms: association with incidenceof depression as measured by hospital admission, Te BritishJournal of Psychiatry, vol. 164, no. 3, pp. 403409, 1994.[70]M. Berk, S. Dodd, and M. Henry, Do ambient electromagneticfeldsafectbehaviour?Ademonstrationoftherelationshipbetween geomagnetic storm activity and suicide, Bioelectro-magnetics, vol. 27, no. 2, pp. 151155, 2006.BioMed Research International 11[71]J. R. Gray, C. H. Frith, and J. D. Parker, In vivo enhancement ofchemotherapy with static electric or magnetic felds, Bioelectro-magnetics, vol. 21, no. 8, pp. 575583, 2000.[72]M. Zmyslony, J. Palus, J. Jajte, E. Dziubaltowska, and E.Rajkowska, DNA damage in rat lymphocytes treated in vitrowith iron cations and exposed to 7 mT magnetic felds (static or50 Hz), Mutation Research, vol. 453, no. 1, pp. 8996, 2000.[73]J. Jajte, J. Grzegorczyk, M. Zmysacute, andE. Rajkowska,Efect of 7 mTstaticmagneticfeldandironions onratlymphocytes:apoptosis,necrosis and free radical processes,Bioelectrochemistry, vol. 57, no. 2, pp. 107111, 2002.[74]B. Tenuzzo, C. Vergallo, andL. Dini, Efectof6 mTstaticmagnetic feld on the bcl-2, bax, p53 and hsp70 expression infreshly isolated and in vitro aged human lymphocytes, Tissueand Cell, vol. 41, no. 3, pp. 169179, 2009.[75]C. Fanelli, S. Coppola, R. Barone et al., Magnetic felds increasecell survival by inhibiting apoptosis via modulation of Ca2+infux, Te FASEB Journal, vol. 13, no. 1, pp. 95102, 1999.[76]M. de Nicola, S. Cordisco, C. Cerella et al., Magnetic feldsprotect from apoptosis via redox alteration, Annals of the NewYork Academy of Sciences, vol. 1090, pp. 5968, 2006.[77]D. Flipo, M. Fournier, C. Benquet et al., Increased apoptosis,changes inintracellular Ca2+, andfunctional alterations inlymphocytes and macrophages afer in vitro exposure to staticmagnetic feld, Journal of Toxicology and Environmental HealthA, vol. 54, no. 1, pp. 6376, 1998.[78]R. Ishisaka, T. Kanno, Y. Inai et al., Efects of a magnetic feldson the various functions of subcellular organelles and cells,Pathophysiology, vol. 7, no. 2, pp. 149152, 2000.[79]L. Teodori, J. Grabarek, P. Smolewski et al., Exposure of cellsto static magnetic feld accelerates loss of integrity of plasmamembrane during apoptosis, Cytometry, vol. 49, no. 3, pp. 113118, 2002.[80]L. Teodori, W. G ohde, M. G. Valente et al., Static magneticfelds afect calcium fuxes and inhibit stress-induced apoptosisin human glioblastoma cells, Cytometry, vol. 49, no. 4, pp. 143149, 2002.[81]L. Teodori, M. C. Albertini, F. Uguccioni et al., Static magneticfelds afect cell size, shape, orientation, and membrane surfaceof human glioblastoma cells, as demonstrated by electron, optic,and atomic force microscopy, Cytometry A, vol. 69, no. 2, pp.7585, 2006.[82]L. Potenza, C. Martinelli, E. Polidori et al., Efects of a 300 mTstatic magnetic feld on human umbilical vein endothelial cells,Bioelectromagnetics, vol. 31, no. 8, pp. 630639, 2010.[83]Q. Hao, C. Wenfang, A. Xiaetal., Efectsofamoderate-intensity static magnetic feld and adriamycin on K562 cells,Bioelectromagnetics, vol. 32, no. 3, pp. 191199, 2011.[84]A. S. Sarvestani, P. Abdolmaleki, S. J. Mowlaet al., Staticmagnetic felds aggravate the efects of ionizing radiation on cellcycle progression in bone marrow stem cells, Micron, vol. 41,no. 2, pp. 101104, 2010.[85]J. McCann, F. Dietrich, C. Raferty, and A. Martin, A criticalreviewof thegenotoxicpotential of electricandmagneticfelds, Mutation Research, vol. 297, no. 1, pp. 6195, 1993.[86]Y. Suzuki, M. Ikehata, K. Nakamura et al., Inductionofmicronuclei in mice exposed to static magnetic felds, Muta-genesis, vol. 16, no. 6, pp. 499501, 2001.[87]J. W. Lee, M. S. Kim, Y. J. Kim, Y. J. Choi, Y. Lee, and H. W.Chung, Genotoxic efects of 3 T magnetic resonance imagingin cultured human lymphocytes, Bioelectromagnetics, vol. 32,no. 7, pp. 535542, 2011.[88]W. G. Schreiber, E. M. Teichmann, I. Schifer et al., Lack ofmutagenic and co-mutagenic efects of magnetic felds duringmagnetic resonance imaging, Journal of Magnetic ResonanceImaging, vol. 14, no. 6, pp. 779788, 2001.[89]N. F. Schwenzer, R. Bantleon, B. Maurer et al., Detection ofDNA double-strand breaks using H2AX afer MRI exposureat 3 Tesla:an in vitro study, Journal of Magnetic ResonanceImaging, vol. 26, no. 5, pp. 13081314, 2007.[90]H. Okonogi, M. Nakagawa, and Y. Tsuji, Te efects of a 4.7tesla static magnetic feld on the frequency of micronucleatedcells induced by mitomycin C, Te Tohoku Journal of Experi-mental Medicine, vol. 180, no. 3, pp. 209215, 1996.[91]T. Kimura, K. Takahashi, Y. Suzuki et al., Te efect ofhigh strength static magnetic felds and ionizing radiation ongene expression and DNA damage in Caenorhabditis elegans,Bioelectromagnetics, vol. 29, no. 8, pp. 605614, 2008.[92]T. Koana, M. O. Okada, M. Ikehata, and M. Nakagawa,Increase in the mitotic recombination frequency in Drosophilamelanogaster by magnetic feld exposure and its suppression byvitamin E supplement, Mutation Research, vol. 373, no. 1, pp.5560, 1997.[93]U. Graf, F. E. Wurgler, and A. J. Katz, Somatic mutation andrecombination test in Drosophila melanogaster, EnvironmentalMutagenesis, vol. 6, no. 2, pp. 153188, 1984.[94]M. Ikehata, T. Koana, Y. Suzuki, H. Shimizu, and M. Nakagawa,Mutagenicityandco-mutagenicityof staticmagneticfeldsdetected by bacterial mutation assay, Mutation Research, vol.427, no. 2, pp. 147156, 1999.[95]T. Nakahara, H. Yaguchi, M. Yoshida, and J. Miyakoshi, Efectsof exposure of CHO-K1 cells to a 10-T static magnetic feld,Radiology, vol. 224, no. 3, pp. 817822, 2002.[96]S. Tofani, D. Barone, M. Berardelli et al., Static and ELF mag-netic felds enhance the in vivo anti-tumor efcacy of cis-platinagainstlewislungcarcinoma, butnotofcyclophosphamideagainst B16 melanotic melanoma, Pharmacological Research,vol. 48, no. 1, pp. 8390, 2003.[97]R. G. Sun, W. F. Chen, H. Qi et al., Biologic efects of SMF andpaclitaxel on K562 human leukemia cells, General Physiologyand Biophysics, vol. 31, no. 1, pp. 110, 2012.[98]S. Strieth, D. Strelczyk, M. E. Eichhorn et al., Static magneticfeldsinducebloodfowdecreaseandplateletadherenceintumor microvessels, Cancer Biology & Terapy, vol. 7, no. 6, pp.814819, 2008.[99]D. Strelczyk, M. E. Eichhorn, S. Luedemannet al., Staticmagnetic felds impair angiogenesis and growth of solid tumorsin vivo, Cancer Biology and Terapy, vol. 8, no. 18, pp. 17561762, 2009.[100]W. F. Chen, H. Qi, R. G. Sun, Y. Liu, K. Zhang, and J. Q. Liu,Static magnetic felds enhanced the potency of cisplatin onK562 cells, Cancer Biotherapy and Radiopharmaceuticals, vol.25, no. 4, pp. 401408, 2010.[101]Y. Liu, H. Qi, R. G. Sun, and W. F. Chen, An investigationinto the combined efect of static magnetic felds and diferentanticancer drugs on K562 cell membranes, Tumori, vol. 97, no.3, pp. 386392, 2011.[102]R. R. Raylman, A. C. Clavo, and R. L. Wahl, Exposure to strongstatic magnetic feld slows the growth of human cancer cells invitro, Bioelectromagnetics, vol. 17, no. 5, pp. 358363, 1996.[103]A. Chionna, B. Tenuzzo, E. Panzarini, M. B. Dwikat, L. Abbro,and L. Dini, Time dependent modifcations of Hep G2 cellsduring exposure to static magnetic felds, Bioelectromagnetics,vol. 26, no. 4, pp. 275286, 2005.12 BioMed Research International[104]S. W. Feng, Y. J. Lo, W. J. Chang et al., Static magnetic feldexposure promotes diferentiationof osteoblastic cells grownonthe surface of a poly-L-lactide substrate, Medical & BiologicalEngineering & Computing, vol. 48, no. 8, pp. 793798, 2010.[105]S. H. Hsu and J. C. Chang, Te static magnetic feld acceleratesthe osteogenic diferentiation and mineralization of dental pulpcells, Cytotechnology, vol. 62, no. 2, pp. 143155, 2010.[106]C. F. Martino, L. Portelli, K. McCabe, M. Hernandez, and F.Barnes, Reduction of the Earths magnetic feld inhibits growthrates of model cancer cell lines, Bioelectromagnetics, vol. 31, no.8, pp. 649655, 2010.[107]J. C. Yang, S. Y. Lee, C. A. Chen, C. T. Lin, C. C. Chen, and H.M. Huang, Te role of the calmodulin-dependent pathway instatic magnetic feld-induced mechanotransduction, Bioelec-tromagnetics, vol. 31, no. 4, pp. 255261, 2010.[108]J. Sabo, L. Mirossay, L. Horovcak, M. Sarissky, A. Mirossay, andJ. Mojzis, Efects of static magnetic feld on human leukemiccell line HL-60, Bioelectrochemistry, vol. 56, no. 1-2, pp. 227231, 2002.[109]L. Ghibelli, C. Cerella, S. 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