[AI] Cell phone & the cell

Shadab Husain shadabhsn at gmail.com
Thu May 1 02:40:28 EDT 2008


Cell phone & the cell

R. RAMACHANDRAN

On recent studies in Finland, the land of Nokia.

THE widespread use of mobile, or cell, phones has been accompanied by
controversy over the adverse health effects of the electromagnetic
field (EMF) radiation
emitted by them. The controversy remains despite years of research.
Most of the claimed effects, and the consequent research that these
have triggered,
have to do with genotoxicity, mutations, cancer and male sterility.
But there are also reports about mobile phone radiation, whose
frequencies (900–1,800
megahertz, or MHz) are in the microwave region of the EM spectrum (see
diagram), causing such non-life-threatening ailments as sleep
disorders, headaches
and allergic symptoms.

A series of studies by a research team led by Dariusz Leszczynski, at
STUK, the Finnish Radiation and Nuclear Safety Authority, Helsinki,
has now demonstrated
that the radiation emitted by ordinary mobile phones – which is
essentially a low-energy radio-frequency-modulated EMF (RF-EMF) – can
cause subtle biological
effects in tissues, such as alteration in the protein expression of
certain genes active in the exposed tissues and increased
phosphorylation (which is
the addition of phosphate groups to proteins and is a measure of their
biochemical activity). Following earlier in vitro experiments with
human cell lines,
Leszczynski's team has now demonstrated for the first time that such
molecular level changes occur in human tissues in vivo too.

In this experiment, a small area of skin on the forearm of 10 female
volunteers was exposed for one hour to a 900 MHz GSM (Global System
for Mobile communication)
signal of strength similar to a normal mobile phone's signal. The
response of the skin tissue to this RF-EMF was studied by carrying out
biopsies for all
extractable proteins on exposed and non-exposed areas of skin. This
was done with a technique known as two-dimensional electrophoresis
(2-DE). The technique
came up with 579 proteins, an analysis of which identified eight
proteins, two of which were common to all the volunteers, that were
statistically significantly
altered. The results of the experiment were published on February 11
in BioMed Central's open access online journal BMC Genomics. According
to the authors,
the results were similar to those seen in their earlier in vitro
experiments. Since findings in vitro do not necessarily imply that
similar responses would
be seen in living tissues as well, this in vivo study strengthens
their earlier findings.

It is generally believed that radiation from mobile phones is unlikely
to cause any biological effects. A major reason for this belief is
that the energy
deposited in a tissue by a mobile phone is far lower than the energy
needed to break a chemical bond, which is about one electronvolt (eV).
The energy
required to knock off electrons from a molecule is an order of
magnitude higher, about 10 eV. Electromagnetic energy is carried by
photons. The higher
the frequency, the higher the energy in each photon (see diagram). The
frequency at which the radiation becomes ionising is around the upper
end of the
ultraviolet (UV) range, a little below the frequency where X-rays begin.

Thus, the energy carried by a 900 MHz GSM mobile phone (4 × 10-6 eV)
or by a 1,800 MHz GSM mobile phone (7 × 10-6 eV) is about a million
times less than
that required to cause chemical reactions. Nevertheless, at high
intensities, all non-ionising radiation – for instance, extreme low
frequency (ELF) fields
such as those produced by high voltage electrical wires, RF,
microwaves, infrared, visible light and low-frequency UV – can cause
heating of the material
on which the energy is deposited, including tissues. For this reason,
safety regulations for RF and microwave devices fix their exposure
levels on the
basis of their well-understood thermal effects when sufficient energy
is deposited to cause a measurable increase in the temperature of the
sample. Therefore,
many question whether this low energy would be able to induce
biological effects at all, and since the physical mechanism remains
unknown, the biological
effects reported are often dismissed as artefacts of the experiment,
Leszczynski points out in a paper.

But there are many animal and in vitro studies on mobile phone
exposure that suggest the possibility of non-thermal biological
effects such as levels of
expression and activity of certain proteins, which get activated by
external stress even when it is too small to cause a rise in
temperature. The well-known
British report (2000) by the Independent Expert Group on Mobile Phones
of the erstwhile National Radiological Protection Board, headed by Sir
William Stewart,
and the report of the expert panel of the Royal Society of Canada
(1999) took cognisance of such findings and advocated a precautionary
approach to the
use of wireless devices pending definitive proof of their potential
health risks. The Finnish study should, therefore, be viewed as one
that has gone a
step further through its in vivo findings in humans.

In the first of the earlier studies done in 2002, and reported in the
journal Differentiation, Leszczynski's team exposed a human
endothelial cell line
(a single layer of smooth, flattened cells characteristic of the
linings of the heart, blood vessels and lymph vessels) called EA.hy926
to a 900 MHz GSM
mobile phone for one hour to see whether the signal activated a stress
response much like the higher energy EMFs. The unit that is commonly
used to measure
the energy deposited in biological systems is the specific absorption
rate (SAR), which is defined in watts per kilogram (W/kg) and is the
rate of absorption
of EM energy in a unit mass of tissue. In the experiment, the
GSM-mobile-phone-simulating signal was maintained at a SAR of 2.4
W/kg, which is slightly
above the European safety limit of 2.0 W/kg.

One of the proteins affected in the study was identified as heat-shock
protein-27 (Hsp27). It was found that mobile phone exposure caused a
transient increase
(two- to sevenfold) in the phosphorylation of Hsp27, which was
prevented by a specific inhibitor called SB203580 derived from a
protein kinase designated
as p38 mitogen-activated protein kinase (p38 MAPK). (Protein kinases
are enzymes that activate phosphorylation and MAPKs are protein
kinases that respond
to external stimuli and regulate cellular processes.) It was also
found that the exposure caused transient changes in the protein
expression levels of
Hsp27 (twofold) and p38 MAPK.

The observed increase in the expression and phosphorylation of Hsp27
in cells led the researchers to suggest that the cells in EA.hy926 had
recognised RF-EMF
as an external stress factor and this is what elicited an
Hsp27-dependent defence. All these effects were non-thermal because,
as was determined using
temperature probes, irradiation intensity was maintained at levels so
as to not alter the temperature of the cell culture, which remained
throughout the
irradiation period at 37 ± 0.3° C. On the basis of this finding, the
researchers suggested that mobile phone radiation activated a variety
of cellular
signal transduction pathways, the stress response pathway involving
Hsp27 and p38 MAPK being one of them.

Heat-shock proteins are a class of proteins that get expressed as a
result of cell response to external stress factors, such as heat and
radiation, including
intense sunlight. The response is designed to be the cell's defence
mechanism against the external stress. Changes in protein expression
and phosphorylation
levels can be detected within seconds of exposure, according to
Leszczynski. The difference between these detectable cellular
responses and RF-EMF-induced
stress is that, as noted earlier, the energy deposited by heat
(infrared), sunlight (visible light) or UV radiation is far greater
than that of microwave
or radio frequency radiation.

In a paper on "Activation of cellular stress response by RF-EMF and
its possible impact on cell physiology", Leszczynski noted:
"Comparison of the extent
of RF-EMF-induced stress response (weak stimulus) with the extent of
stress response induced by heat (strong stimulus) for the purpose of
claims that the
RF-EMF-induced stress is negligible is incorrect; it would be like
comparing response to 'tickling with feeder' with response to 'hitting
with hammer'."
In an e-mail communication, Leszczynski pointed out that such a
quantitative comparison was difficult because classical heating and
heating with microwaves
had different kinetics. The new finding of Leszczynski's group is that
even the weak stimulus of RF-EMF-induced stress is sufficient to
elicit a cellular
response in Hsp27 and associated biochemical pathways.
Shrinking of cells

Investigating further whether these changes had any impact on cellular
physiology, the scientists examined the status of stress fibres in the
exposed cells
because phosphorylation of Hsp27 was known to regulate the stability
of certain (F-actin) stress fibres.

It was found that the stability of the stress fibres increased after
the period of irradiation and did not decline during the subsequent
one-hour incubation
period. This induction of increased stability of stress fibres, which
could be prevented by the inhibitor SB203580, was found to cause cells
to visibly
shrink. On the basis of this finding, the researchers hypothesised
that increased stabilisation of stress fibres and the cell shrinking
caused by it, if
they occurred in the endothelial lining of brain's blood vessels,
might have an effect on the functioning of the blood-brain barrier.
This they observed
could explain the increased permeability of the blood-brain barrier in
certain animal experiments under RF-EMF exposure.

Exposure of forearm with a dipole antenna at 900 MHz.

They further noted that Hsp27's overexpression and increased
phosphorylation also resulted in inhibition of programmed cell death,
or apoptosis, owing to
the formation of a new chemical complex with the protein complex
apoptosome. This, they hypothesised, could support the survival of
cells that transformed
spontaneously or were damaged by external factors. The study also
found changes in certain proteins of the cytoskeleton (the scaffolding
or the skeleton
of the cytoplasm in the cells).

The cell line showed up as many as 1,300 altered proteins by the 2-DE
technique, of which 49 were found to be statistically significantly
altered. Among
these 49 were certain cytoskeletal proteins known as vimentins. Thus,
the upshot of the experiment is that there is a possibility that
RF-EMF-induced molecular
events could lead to alteration in cell physiology. "Whether any
impact on organs or whole body will be exerted by this change remains
to be determined
by in vivo studies," the researchers noted. This set the stage for the
human volunteer project, and as a first step, human skin cells were
exposed to low-energy
RF-EMF from mobile phones.

To an e-mail query whether exposure to higher energy EM radiation,
such as heat or sunlight, would result in similar
blood-brain-barrier-related and apoptotic
effects, Leszczynski said: "Obviously, sunlight has no effect on the
blood-brain barrier, at least directly." He further emphasised that
the effects on
stress proteins and stress fibres induced by mobile phone radiation
were transient and cells returned to their normal state after a few
hours. "Whether
repeated exposures could lead to a permanent up-regulation of the
stress status of cells, we simply do not know," he added.

Since we know that continuous exposure to higher energy sunlight and
heat (particularly in tropical and desert climates) causes no other
long-term remarkable
physiological changes in general populations (except in the cases of
heat strokes, which can be fatal and in cases where UV exposure of
non-melanin-rich
populations can cause skin cancer in the long term), one could argue a
priori that mobile phones are unlikely to cause any long-term health
impact. "No,"
Leszczynski said in his e-mail response. "It is not correct because
mobile phone radiation might induce non-thermal effects. Furthermore,
body physiology
has mechanisms to adjust to increased temperature caused by slow
heating (sunshine). Heating with microwaves is fast and the body has
no time to adjust
physiology so fast. Therefore, the responses in respect to health
might be different. However, this is only a hypothesis, and we do not
know whether it
is correct. We simply do not have studies that would examine such a
possibility."

In another related study, Leszczynski and colleagues carried out the
same experiment on two closely related variants of the human
endothelial cell line:
EA.hy296 and EA.hy296v1. While they found that gene and protein
expression were altered in both the cell lines in response to a
one-hour radiation exposure
at an average SAR of 2.8 W/kg, it was found that the same genes and
proteins were affected by the exposure differently. "Therefore," the
researchers observed
an important facet of the biological effects seen, "it is likely that
different types of cells and from different species might have
different sensitivity
to this weak stimulus. Our findings might also explain, at least in
part, the origin of discrepancies in replication studies between
different laboratories."

ARUNANGSU ROY CHOWDHURY

The energy carried by mobile phones is about a million times smaller
than that required to cause chemical reactions.

In all these studies, Leszczynski and associates made a paradigm shift
in the technique used for such analyses. Conventional methods are not
suited for
detecting the small changes in protein expression or phosphorylation
that could occur because of "weak stimuli", such as RF-EMF-induced
stress, and which
might be insufficient to cause any physiological changes or potential
health effects, as against effects due to "strong stimuli". The
researchers employed
the new approach of high throughput screening techniques (HTST) that
have come into use with the increasing automation in biological
laboratory methods.
This allows a researcher to carry out thousands of biochemical,
pharmacological or genetic tests rapidly on samples at hand. Using
this technique, one
can quickly identify active compounds, antibodies or genes that are
involved in a particular biomolecular pathway. This technique has come
particularly
into vogue in the fields of proteomics (the study of all protein
expressions in a given population of cells) and transcriptomics (the
study of the expression
of all the genes at a time), which have emerged as the natural next
steps to derive maximum knowledge out of genomics (the deciphering of
complete genomes
of organisms).

In an editorial in Proteomics in 2006, before the latest in vivo
experiment, Leszczynski pointed out that finding and validating any
potential health hazard
using the normal epidemiological approach might not be possible
because of the "low sensitivity" of the methodology, which would be
insufficient to reliably
detect the weak biological effects of low-energy EMF. Further, he
pointed out that most epidemiological studies are focussed on the
induction of cancer.
"Therefore, independent of their outcome, these studies will provide
information only about cancer," he wrote.

"The research executed so far," he said in the editorial, "has not
produced convincing or robust evidence about the possibility of
induction of biological
effects by mobile phone radiation….The use of HTST…might be a useful
approach to determine possible molecular targets of EMF on the
sub-cellular level.
The HTST approach seems to be particularly well suited for studying
biological effects of EMF because it might reveal effects that are not
possible to
predict based on the presently available knowledge…. [I]t is necessary
to remember that HTST can pick up small changes in protein or gene
expression which
might be of insufficient magnitude to alter cell physiology…. [T]he
use of the HTST approach will likely lead to the identification of
cellular signalling
pathways that respond to EMF exposure. This will allow the formulation
of much better, knowledge-based hypotheses aimed at determining
whether there might
be any health hazard associated with the EMF exposures." Thus, the
method of using genome-wide and proteome-wide screening techniques was
aimed at quickly
identifying all the genes and proteins that respond to low-energy
RF-EMF rather than detecting any possible health effects. The human
volunteer project
has demonstrated that living human skin does respond to mobile phone radiation.

"The human volunteer studies conducted so far," the authors point out
in the paper, "have focussed on cognitive responses to RF-EMF and
there is no information
available about the proteome, as well as the transcriptome, response
to mobile phone radiation in humans." Their findings imply that the
response of human
skin to RF-EMF results in the alteration of protein expression.
However, as they emphasise, this does not necessarily mean that these
observed biochemical
changes would have any effect on health or cell physiology. This, they
point out, requires a further, larger study. Accordingly, a more
extensive study
with 50-100 volunteers is now planned at STUK. Depending upon the
availability of funding, they plan to launch the study in 2009. The
present study was
funded by Tekes (the Finnish Funding Agency for Technology and
Innovation) and STUK, and it was a part of the Finnish research
programme on Health Risk
Assessment of Mobile Communications (HERMO).•

http://www.frontlineonnet.com/stories/20080509250909900.htm




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