This review paper summarizes research on the effects of cell phone electromagnetic radiation exposure on the brain. Several studies found associations between long-term cell phone use (>10 years) and brain tumor development, especially on the side of the head most used. Exposure has been shown to up-regulate cell death pathways in neurons and affect neural function in humans. It may also cause oxidative damage to neuronal mitochondrial DNA and alter blood-brain barrier permeability. Additionally, cell phone radiation was found to change the oxygen affinity and structure of hemoglobin as well as disrupt inter-hemispheric brain synchronization. While some studies found no effects, overall the review indicates that cell phone use may pose brain-related health risks.

1. Review Paper
Cell Phone Use and Brain-Related Problems
Lester J. Rosario Rodríguez
University of Puerto Rico, Cayey Campus
Department of Biology
Abstract
Scientists support the idea that exposure to electromagnetic fields could has a
negative 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 in
use over the years. Today there are several studies whose purposes are to find if there is
any association between cell phones use and brain-related problems on humans. This
review provides information about the different effects that exposure to electromagnetic
radiation has on human brain. In resume, the problems found in some researches are
associated with: the developing of malignant tumors and acoustic neuroma, the
dysregulation of gene expression related to cell death pathways in neurons and astrocytes,
the negative effects on neural function, the oxidative damage to mitochondrial DNA in
primary cultured neurons, the albumin extravasation over the blood-brain barrier, and the
alteration of oxygen affinity and tertiary structure of human hemoglobin.
1. Introduction
1.1 Cell Phones and Electromagnetic Radiation (EMR)
Cell phones are one of today’s great advances in technology. This gadget was
created to satisfy people’s need for communication in an easier way; in order that they
could communicate being geographically distant. The cell phones are now part of a
person’s daily life. Today about a half of the people all around the world are cell phone
users (Nittby et al. 2009). The society knows how to use them, but many of the people
don’t know how they work.
Cell phone technology incorporates base stations, namely, transmission tower
antennae, and cell phone hand-held units. Cell phone networks were first deployed in
Sweden in 1981 via the Nordic Mobile Telephone System (analogue; 450 MHz; first
generation or ―1G‖). The digital system (Global System for Mobile Communication, or
GSM) 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 1900
MHz; called the ―3G‖. Cell phone base stations or masts emit electromagnetic radiations
(EMR) continuously and at far greater power than cell phones which emit EMR
continuously only during calls. Between calls or ―at rest‖ with the ―screen asleep‖ but the
power on, cell phones emit a regular pulse of EMR in order for base stations to
continuously 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 and
a magnetic field generated by the flow of current. The field propagates at the speed of light
in waves of a certain length that oscillate at a certain frequency. In the electromagnetic
range, gamma rays given off by radioactive materials, cosmic rays, and x-rays are all
dangerous to humans and other organisms because of the relatively high-energy they carry
via 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 via
EMR 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 relatively
low-frequency or long-wavelength waves that are ―nonionizing‖ because of insufficient
energy to break intermolecular bonds. (Nittby et al. 2009). In spite of that, the relationship
between exposure to electromagnetic fields (ELFs) and brain tumor incidence has long
been 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 complex
organ. The brain monitors and regulates the body's actions and reactions. It continuously
receives sensory information, and rapidly analyzes this data and then responds, controlling
bodily actions and functions. The central nervous system (CNS) is the part of the nervous
system 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 except
sponges and radially symmetric animals such as jellyfish. It contains the majority of the
nervous system and consists of the brain and the spinal cord. The central nervous system
consists of neurons and glial cells. Neurons constitute about half the volume of the CNS
and glial cells make up the rest. The four main functions of glial cells are: to surround
neurons and hold them in place, to supply nutrients and oxygen to neurons, to insulate one
neuron from another, and to destroy and remove the carcasses of dead neurons. The
astrocytes are one type of the glial cells of the central nervous system. The peripheral
nervous system, or PNS, consists of the nerves and ganglia outside of the brain and the
spinal 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 nervous
system. These cells are involved in: the conduction of nervous impulses along axons, nerve
development and regeneration, trophic support for neurons, production of the nerve
extracellular matrix, modulation of neuromuscular synaptic activity, and presentation of
antigens to T-lymphocytes. (Hardell et al. 2009). Worldwide use of cell phones has raised
concerns that such technology may increase the risk of malignant brain tumors and of
acoustic neuroma (AN), a benign tumor arising from the eighth cranial nerve that leads
from the brain to the inner ear. (Han 2009). Also there are other brain-related problems
associated 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 and
collaborators in 2007 associated long-term use of cell phones (>10 years) with the
development of glioma and acoustic neuroma. The study was of limited value due to
methodological 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. An
association with acoustic neuroma was found in four studies in the group with at least 10
years’ use of a mobile phone. No risk was found in one study, but the tumor size was
significantly larger among users. Six studies gave results for malignant brain tumors in that
latency group. All gave increased odd ratios (OR), especially for ipsilateral exposure (the
side of the head where the mobile phone is used). However, there are several studies where
no association or significance has been found.
3. Neurons
A dysregulation of gene expression related to cell death pathways in neurons and
astrocytes was associated with exposure to GSM mobile phones at a frequency of 1900
MHz. The results showed that even relatively short-term exposure to cell phone
radiofrequency emissions can up-regulate elements of apoptotic pathways in cells derived
from 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 that
exposure to an active mobile phone (MP) affects human neural function.
Cells communicate with each other producing tiny electrical impulses. These
impulses can be measured by an electroencephalogram (EEG), placing electrodes on the
scalp. In this research, twenty-four subjects participated in a single-blind fully
counterbalanced cross-over design, where both resting EEG (eyes closed) and phase-locked
neural responses to auditory stimuli were measured while a MP was either operating or
turned off. MP exposure altered resting EEG, decreasing 1–4 Hz activity (right
hemisphere 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 the
response in the 12-30 Hz band globally and as a function of time, and increasing midline
frontal and lateral posterior responses in the 30–45 Hz band. In conclusion, active MPs
affect neural function in humans and do so as a function of exposure duration. The temporal
nature of this effect may contribute to the lack of consistent results reported in the
literature. In 2007, it was reported that GSM electromagnetic fields (GSM-EMFs) of
mobile phones modulate – after a prolonged exposure – inter-hemispheric synchronization
of temporal and frontal resting electroencephalographic (EEG) rhythms in normal young
subjects (Vecchio et al. 2007). Later, in 2010, another group directed by Vecchio found
that 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 the
GSM condition, comparing them with the young subjects. This means that physiological
aging 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 reactive
oxygen species (ROS) and a biological system's ability to readily detoxify the reactive
intermediates or to repair the resulting damage. Increasing evidence indicates that
oxidative stress may be involved in the adverse effects of radiofrequency (RF) radiation on
the 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 at
a 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 a
significant increase in the levels of 8-hydroxyguanine (8-OHdG), a common biomarker of
DNA oxidative damage, in the mitochondria of neurons. Concomitant with this finding, the
copy number of mtDNA and the levels of mitochondrial RNA transcripts showed an
obvious reduction after RF exposure. These results suggested that 1800 MHz RF radiation
could cause oxidative damage to mtDNA in primary cultured neurons. Oxidative damage to
mtDNA 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 intensity
electromagnetic field (EMF) inducesROS production and DNA fragmentation in astrocytes
in 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 the
capillaries of the brain and the glial cells wrapped around them. An intact BBB is
necessary for the protection of the mammalian brain from potentially harmful substances
circulating in the blood. In the normal brain, the passage of compounds over the BBB is
highly restricted and homeostasis within the sensitive environment of the brain parenchyma
can be maintained. In a research, forty-eight rats were exposed in TEM-cells for 2 h at
non-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, neuronal
albumin uptake and neuronal damage were assessed. There was a low, but significant
correlation between the exposure level (SAR-value) and occurrence of focal albumin
extravasation (Nittby et al. 2009). Another study found that after exposing humans for 30
minutes to a mobile phone the serum levels of transthyretin (a cerebrospinal fluid carrier of
the thyroid hormone thyroxine and retinol) increased in the last blood sample recollected
after 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 from
the lungs to the tissues. Seyed and collaborators in 2009 investigated the effects of mobile
phone radiofrequency (910 MHz and 940 MHz) on the structure and function of
hemoglobin (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 mobile
phone 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 of
exposure.

5. Conclusions
There are significant results of researches that associate exposure to electromagnetic
fields of cell phones with brain-related problems. An association with acoustic neuroma
was found in four studies with at least 10 years’ use of a mobile phone. Another six studies
gave results for malignant brain tumors within the same period of time. All those studies
gave results especially for ipsilateral exposure (the side of the head where the mobile phone
is used). However, there are several studies where no association or significance has been
found. 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-regulate
elements of apoptotic pathways in cells derived from the brain, and that neurons appear to
be more sensitive to this effect than astrocytes. Two reasearches suggest that active mobile
phones 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 functional
organization of cortical neural synchronization (in the brain). A research suggests that
1800 MHz radiofrequency radiation could cause oxidative damage to mtDNA in primary
cultured neurons. Also it was found in another study that even acute exposure to low
intensity electromagnetic field (EMF) induces reactive oxygen species production and
DNA 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 the
exposure level and occurrence of focal albumin extravasation over the BBB. Finally, it was
found that mobile phone electromagnetic fields (910 MHz and 940 MHz) altered oxygen
affinity and tertiary structure of human hemoglobin (HbA). The decrease of oxygen
affinity 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, Vanella
A,Triglia A. 2010. Reactive oxygen species levels and DNA fragmentation on astrocytes in
primary culture after acute exposure to low intensity microwave electromagnetic field
Neuroscience Letters 493(1): 52-53
Croft R, Chandler J, Burgess A, Barry R, Williams J, Clarke A. 2002. Acute mobile phone
operation affects neural function in humans. Clinical Neurophysiology 113(10): 1623-1632
Han Y, Kano H, Davis D, Niranjan A, and Lunsford L. 2009. Cell phone use and acoustic
neuroma: the need for standardized questionnaires and access to industry data. Surgical
Neurology 72(3): 216-222
Hardell L, Carlberg M, Söderqvist F, Mild K, Morgan L. 2007. Long-term use of cellular
phones and brain tumours: increased risk associated with use for ≥10 years. Occupational
and Environmental Medicine 64: 626-632
Hardell L, Carlberg M, Mild K. 2009. Epidemiological evidence for an association
between 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. Increased
blood–brain barrier permeability in mammalian brain 7 days after exposure to the radiation
from a GSM-900 mobile phone. Pathophysiology 16(2-3): 103-112.
Pawl R. 2008. Cell phones more dangerous than cigarettes! Surgical Neurology 70(5):
445-446
Seyed M, Gholam R, Mahmood K, Hadi A, Naghmeh S, Ahmad S, Shahrokh S, Faizan A
and Ali M. 2009. Effects of mobile phone radiofrequency on the structure and function of
the normal human hemoglobin. International Journal of Biological Macromolecules
44(3):278-285.
Söderqvist F, Carlberg M, Mild K,Hardell L. 2009. Exposure to an 890-MHz mobile
phone-like signal and serum levels of S100B and transthyretin in volunteers. Toxicology
Letters 189(1): 63-66
Vecchio F,Babiloni C,Ferreri F, Buffo P,Cibelli G, Curcio G, Dijkman S, Melgari J,
Giambattistelli F, Rossini P. 2010. Clinical Neurophysiology 121(2): 163-171
Xu S, Zhou Z, Zhang L, Yung Z, Zhang W, Wang Y, Wang X, Li M, Chen Y, Chen C, He
M, Zhang G, Zhong M. 2010. Exposure to 1800 MHz radiofrequency radiation induces
oxidative damage in mitochondrial DNA in primary cultured neurons. Brain Research
1311: 189-196
Zhao T, Zou S, Knapp P. 2007. Exposure to cell phone radiation up-regulates apoptosis
genes in primary cultures of neurons and astrocytes. Neuroscience Letters 412(1): 34-38