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

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

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

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.

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.

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