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Review Paper 1



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  • 1. Review Paper Cell Phone Use and Brain-Related Problems Lester J. Rosario Rodríguez University of Puerto Rico, Cayey Campus Department of BiologyAbstract Scientists support the idea that exposure to electromagnetic fields could has anegative effect on human health. Electromagnetic fields are radiated from cell phones(today at frequencies from 800 MHz to 1900 MHz), and this technology has been rising inuse over the years. Today there are several studies whose purposes are to find if there isany association between cell phones use and brain-related problems on humans. Thisreview provides information about the different effects that exposure to electromagneticradiation has on human brain. In resume, the problems found in some researches areassociated with: the developing of malignant tumors and acoustic neuroma, thedysregulation of gene expression related to cell death pathways in neurons and astrocytes,the negative effects on neural function, the oxidative damage to mitochondrial DNA inprimary cultured neurons, the albumin extravasation over the blood-brain barrier, and thealteration of oxygen affinity and tertiary structure of human hemoglobin.1. Introduction1.1 Cell Phones and Electromagnetic Radiation (EMR) Cell phones are one of today’s great advances in technology. This gadget wascreated to satisfy people’s need for communication in an easier way; in order that theycould communicate being geographically distant. The cell phones are now part of aperson’s daily life. Today about a half of the people all around the world are cell phoneusers (Nittby et al. 2009). The society knows how to use them, but many of the peopledon’t know how they work. Cell phone technology incorporates base stations, namely, transmission towerantennae, and cell phone hand-held units. Cell phone networks were first deployed inSweden in 1981 via the Nordic Mobile Telephone System (analogue; 450 MHz; firstgeneration or ―1G‖). The digital system (Global System for Mobile Communication, orGSM) started in 1991, representing the second generation of cell phone systems, or ―2G.‖ The latest system currently in mass deployment is about frequencies of 800 and 1900MHz; called the ―3G‖. Cell phone base stations or masts emit electromagnetic radiations(EMR) continuously and at far greater power than cell phones which emit EMRcontinuously only during calls. Between calls or ―at rest‖ with the ―screen asleep‖ but thepower on, cell phones emit a regular pulse of EMR in order for base stations tocontinuously keep track of the geographic position of the phones in their ―cellular
  • 2. network.‖ An EMF is composed of an electric field generated by differences in voltage anda magnetic field generated by the flow of current. The field propagates at the speed of lightin waves of a certain length that oscillate at a certain frequency. In the electromagneticrange, gamma rays given off by radioactive materials, cosmic rays, and x-rays are alldangerous to humans and other organisms because of the relatively high-energy they carryvia high-frequency or short-wavelength waves. Such rays lead to dangerous ―ionizing‖radiation with an ability to break intermolecular bonds. Cell phone systems also act viaEMR but in the ―microwave‖ or ―radiofrequency‖ range close to that of a microwave oven. These systems are supposedly safe because of the lower-energy they carry via relativelylow-frequency or long-wavelength waves that are ―nonionizing‖ because of insufficientenergy to break intermolecular bonds. (Nittby et al. 2009). In spite of that, the relationshipbetween exposure to electromagnetic fields (ELFs) and brain tumor incidence has longbeen a subject of concern and research in the neurosciences and oncology. (Pawl 2008).1.2 The Brain The human brain is the center of the human nervous system and is a highly complexorgan. The brain monitors and regulates the bodys actions and reactions. It continuouslyreceives sensory information, and rapidly analyzes this data and then responds, controllingbodily actions and functions. The central nervous system (CNS) is the part of the nervoussystem that integrates the information that it receives from, and coordinates the activity of,all parts of the bodies of bilaterian animals—that is, all multicellular animals exceptsponges and radially symmetric animals such as jellyfish. It contains the majority of thenervous system and consists of the brain and the spinal cord. The central nervous systemconsists of neurons and glial cells. Neurons constitute about half the volume of the CNSand glial cells make up the rest. The four main functions of glial cells are: to surroundneurons and hold them in place, to supply nutrients and oxygen to neurons, to insulate oneneuron from another, and to destroy and remove the carcasses of dead neurons. Theastrocytes are one type of the glial cells of the central nervous system. The peripheralnervous system, or PNS, consists of the nerves and ganglia outside of the brain and thespinal cord. The main function of the PNS is to connect the central nervous system (CNS)to the limbs and organs. Schwann cells are the principal glia of the peripheral nervoussystem. These cells are involved in: the conduction of nervous impulses along axons, nervedevelopment and regeneration, trophic support for neurons, production of the nerveextracellular matrix, modulation of neuromuscular synaptic activity, and presentation ofantigens to T-lymphocytes. (Hardell et al. 2009). Worldwide use of cell phones has raisedconcerns that such technology may increase the risk of malignant brain tumors and ofacoustic neuroma (AN), a benign tumor arising from the eighth cranial nerve that leadsfrom the brain to the inner ear. (Han 2009). Also there are other brain-related problemsassociated with the exposure to EMR.2. Brain Tumors: Glioma and Acoustic Neuroma The glioma is a cancer of the brain that begins in glial cells. Hardell andcollaborators in 2007 associated long-term use of cell phones (>10 years) with thedevelopment of glioma and acoustic neuroma. The study was of limited value due tomethodological shortcomings in the study. Of the 16 case–control studies, 11 gave results
  • 3. for ≥10 years’ use or latency period. Most of these results were based on low numbers. Anassociation with acoustic neuroma was found in four studies in the group with at least 10years’ use of a mobile phone. No risk was found in one study, but the tumor size wassignificantly larger among users. Six studies gave results for malignant brain tumors in thatlatency group. All gave increased odd ratios (OR), especially for ipsilateral exposure (theside of the head where the mobile phone is used). However, there are several studies whereno association or significance has been found.3. Neurons A dysregulation of gene expression related to cell death pathways in neurons andastrocytes was associated with exposure to GSM mobile phones at a frequency of 1900MHz. The results showed that even relatively short-term exposure to cell phoneradiofrequency emissions can up-regulate elements of apoptotic pathways in cells derivedfrom the brain, and that neurons appear to be more sensitive to this effect than astrocytes(Zhao et al. 2007). Another research done by Croft and collaborators in 2002 suggests thatexposure to an active mobile phone (MP) affects human neural function. Cells communicate with each other producing tiny electrical impulses. Theseimpulses can be measured by an electroencephalogram (EEG), placing electrodes on thescalp. In this research, twenty-four subjects participated in a single-blind fullycounterbalanced cross-over design, where both resting EEG (eyes closed) and phase-lockedneural responses to auditory stimuli were measured while a MP was either operating orturned off. MP exposure altered resting EEG, decreasing 1–4 Hz activity (righthemisphere sites), and increasing 8–12 Hz activity as a function of exposure duration(midline posterior sites). MP exposure also altered early phase-locked neural responses,attenuating the normal response decrement over time in the 4–8 Hz band, decreasing theresponse in the 12-30 Hz band globally and as a function of time, and increasing midlinefrontal and lateral posterior responses in the 30–45 Hz band. In conclusion, active MPsaffect neural function in humans and do so as a function of exposure duration. The temporalnature of this effect may contribute to the lack of consistent results reported in theliterature. In 2007, it was reported that GSM electromagnetic fields (GSM-EMFs) ofmobile phones modulate – after a prolonged exposure – inter-hemispheric synchronizationof temporal and frontal resting electroencephalographic (EEG) rhythms in normal youngsubjects (Vecchio et al. 2007). Later, in 2010, another group directed by Vecchio foundthat elderly subjects showed a statistically significant (p < 0.001) increment of the inter-hemispheric coherence of frontal and temporal alpha rhythms (about 8–12 Hz) during theGSM condition, comparing them with the young subjects. This means that physiologicalaging is related to changes in the functional organization of cortical neural synchronization.3.1 Oxidative stress The oxidative stress represents an imbalance between the production of reactiveoxygen species (ROS) and a biological systems ability to readily detoxify the reactiveintermediates or to repair the resulting damage. Increasing evidence indicates thatoxidative stress may be involved in the adverse effects of radiofrequency (RF) radiation onthe brain. The mitochondrial DNA (mtDNA) defects are closely associated with various
  • 4. nervous system diseases and mtDNA is particularly susceptible to oxidative stress.Scientists exposed primary cultured cortical neurons to pulsed RF electromagnetic fields ata frequency of 1800 MHz modulated by 217 Hz at an average special absorption rate(SAR) of 2 W/kg. At 24 h after exposure, they found that RF radiation induced asignificant increase in the levels of 8-hydroxyguanine (8-OHdG), a common biomarker ofDNA oxidative damage, in the mitochondria of neurons. Concomitant with this finding, thecopy number of mtDNA and the levels of mitochondrial RNA transcripts showed anobvious reduction after RF exposure. These results suggested that 1800 MHz RF radiationcould cause oxidative damage to mtDNA in primary cultured neurons. Oxidative damage tomtDNA may account for the neurotoxicity of RF radiation in the brain. (Xu et al.2010).According to Campisi and collaborators (2010), even acute exposure to low intensityelectromagnetic field (EMF) inducesROS production and DNA fragmentation in astrocytesin primary cultures, which represent the principal target of modulated EMF.4. The Blood-Brain Barrier (BBB) The Blood-Brain Barrier (BBB) is formed by the vascular endothelial cells of thecapillaries of the brain and the glial cells wrapped around them. An intact BBB isnecessary for the protection of the mammalian brain from potentially harmful substancescirculating in the blood. In the normal brain, the passage of compounds over the BBB ishighly restricted and homeostasis within the sensitive environment of the brain parenchymacan be maintained. In a research, forty-eight rats were exposed in TEM-cells for 2 h atnon-thermal specific absorption rates (SARs) of 0 mW/kg, 0.12 mW/kg, 1.2 mW/kg,12 mW/kg and 120 mW/kg. Albumin extravasation (escape) over the BBB, neuronalalbumin uptake and neuronal damage were assessed. There was a low, but significantcorrelation between the exposure level (SAR-value) and occurrence of focal albuminextravasation (Nittby et al. 2009). Another study found that after exposing humans for 30minutes to a mobile phone the serum levels of transthyretin (a cerebrospinal fluid carrier ofthe thyroid hormone thyroxine and retinol) increased in the last blood sample recollectedafter the exposure. However, the significance of this finding, if any, is unknown(Söderqvist et al. 2009).5. Human Adult Hemoglobin (HbA) Hemoglobin is a protein whose physiological function is to transport oxygen fromthe lungs to the tissues. Seyed and collaborators in 2009 investigated the effects of mobilephone radiofrequency (910 MHz and 940 MHz) on the structure and function ofhemoglobin (HbA). Oxygen affinity was measured by sodium dithionite with Ultraviolet–visible spectrophotometer. Structural changes were studied by circular dichroism(characterizes protein structure) and fluorescence spectroscopy. It was found that mobilephone electromagnetic fields (EMFs) altered oxygen affinity and tertiary structure of HbA. The decrease of oxygen affinity of HbA corresponded to the EMFs intensity and time ofexposure.
  • 5. Conclusions There are significant results of researches that associate exposure to electromagneticfields of cell phones with brain-related problems. An association with acoustic neuromawas found in four studies with at least 10 years’ use of a mobile phone. Another six studiesgave results for malignant brain tumors within the same period of time. All those studiesgave results especially for ipsilateral exposure (the side of the head where the mobile phoneis used). However, there are several studies where no association or significance has beenfound. The results of a study about neurons of the brain showed that even relatively short-term exposure to cell phone radiofrequency emissions (1900 MHz) can up-regulateelements of apoptotic pathways in cells derived from the brain, and that neurons appear tobe more sensitive to this effect than astrocytes. Two reasearches suggest that active mobilephones can affect neural function in humans and do so as a function of exposure duration.Another research suggests that physiological aging is related to changes in the functionalorganization of cortical neural synchronization (in the brain). A research suggests that1800 MHz radiofrequency radiation could cause oxidative damage to mtDNA in primarycultured neurons. Also it was found in another study that even acute exposure to lowintensity electromagnetic field (EMF) induces reactive oxygen species production andDNA fragmentation in astrocytes in primary cultures. About the blood-brain barrier(BBB), it was found in rats that there was a low, but significant correlation between theexposure level and occurrence of focal albumin extravasation over the BBB. Finally, it wasfound that mobile phone electromagnetic fields (910 MHz and 940 MHz) altered oxygenaffinity and tertiary structure of human hemoglobin (HbA). The decrease of oxygenaffinity of HbA corresponded to the EMFs intensity and time of exposure.References:Campisi A, Gulino M, Acquaviva R, Bellia P, Raciti G, Grasso R, Musumeci F, VanellaA,Triglia A. 2010. Reactive oxygen species levels and DNA fragmentation on astrocytes inprimary culture after acute exposure to low intensity microwave electromagnetic fieldNeuroscience Letters 493(1): 52-53Croft R, Chandler J, Burgess A, Barry R, Williams J, Clarke A. 2002. Acute mobile phoneoperation affects neural function in humans. Clinical Neurophysiology 113(10): 1623-1632Han Y, Kano H, Davis D, Niranjan A, and Lunsford L. 2009. Cell phone use and acousticneuroma: the need for standardized questionnaires and access to industry data. SurgicalNeurology 72(3): 216-222Hardell L, Carlberg M, Söderqvist F, Mild K, Morgan L. 2007. Long-term use of cellularphones and brain tumours: increased risk associated with use for ≥10 years. Occupationaland Environmental Medicine 64: 626-632Hardell L, Carlberg M, Mild K. 2009. Epidemiological evidence for an associationbetween use of wireless phones and tumor diseases. Pathophysiology 16(2-3): 113-122
  • 6. Nittby H, Brun A, Eberhardt J, Malmgren L, Persson BR, Leif SG. 2009. Increasedblood–brain barrier permeability in mammalian brain 7 days after exposure to the radiationfrom a GSM-900 mobile phone. Pathophysiology 16(2-3): 103-112.Pawl R. 2008. Cell phones more dangerous than cigarettes! Surgical Neurology 70(5):445-446Seyed M, Gholam R, Mahmood K, Hadi A, Naghmeh S, Ahmad S, Shahrokh S, Faizan Aand Ali M. 2009. Effects of mobile phone radiofrequency on the structure and function ofthe normal human hemoglobin. International Journal of Biological Macromolecules44(3):278-285.Söderqvist F, Carlberg M, Mild K,Hardell L. 2009. Exposure to an 890-MHz mobilephone-like signal and serum levels of S100B and transthyretin in volunteers. ToxicologyLetters 189(1): 63-66Vecchio F,Babiloni C,Ferreri F, Buffo P,Cibelli G, Curcio G, Dijkman S, Melgari J,Giambattistelli F, Rossini P. 2010. Clinical Neurophysiology 121(2): 163-171Xu S, Zhou Z, Zhang L, Yung Z, Zhang W, Wang Y, Wang X, Li M, Chen Y, Chen C, HeM, Zhang G, Zhong M. 2010. Exposure to 1800 MHz radiofrequency radiation inducesoxidative damage in mitochondrial DNA in primary cultured neurons. Brain Research1311: 189-196Zhao T, Zou S, Knapp P. 2007. Exposure to cell phone radiation up-regulates apoptosisgenes in primary cultures of neurons and astrocytes. Neuroscience Letters 412(1): 34-38