EMF EXPERTS DISCUSS EMFS AND VGCCS
From: Joel MOSKOWITZ
Objet: Is
a toxicology model appropriate as a guide for biological research with
electromagnetic fields?
Date: March 16 2015 16:23:11 UTC−4
My
comments: Allan
Frey, a pioneer in the research on the biologic effects of EMF, published this
insightful letter 25 years ago.
Had
governmental agencies followed his advice, it is likely that we would now fully
understand the nonthermal effects of EMF on health, and governments would have
adopted regulatory standards on EMF that protect the health of humans and other
species.
--
Is a
toxicology model appropriate as a guide for biological research with
electromagnetic fields?
Allan H.
Frey. Letter to Editor: Is a toxicology model appropriate as a guide for
biological research with electromagnetic fields? Journal of Bioelectricity.
9(2):233-234. 1990.
"...
most people use a toxicology model as their frame of reference in the selection,
funding, design and analysis of experiments. Data and theory show, however,
that this is the wrong model (2-4). Thus much of the research has inappropriate
or irrelevant. This is one reason why hundreds of millions of dollars have been
spent on EMF biological research with so little return for investment."
" ...
living beings are electrochemical systems that use very low frequency EMFs in
everything from protein folding through cellular communication to nervous
system function."
" ...
if we impose a very weak EMF signal on a living being, it has the possibility
of interfering with normal function if it is properly tuned. This is the model
that much biological data and theory tell us to use, not a toxicology
model."
The letter
can be viewed at: http://bit.ly/AFrey1990
--
Joel M.
Moskowitz, Ph.D.
Director
Center
for Family and Community Health
The UC Berkeley Prevention Research
Center
School of Public Health
University of California, Berkeley
Mail: 50 University
Hall
Berkeley, CA 94720-7360
Phone: 510-643-7314
__________________________________________________
On 2015-03-18 à 05:48, Pall, Martin L wrote:
Dear Andre
Fauteux and others:
I agree that
toxicology is not an appropriate model, in part because there are many dozens
of targets of toxicant action, making this model unnecessarily complex.
Fortunately, EMF action is much simpler. The sole target of EMFs is the
voltage sensor of the voltage regulated ion channels including especially the
calcium channels. This is the target in both animal cells and in
plants. The reason that this is the sole target is that it is millions of
times more sensitive to the fields than are other charged groups in the cell.
So we have
solved this problem and it is time to move on to the many biological
consequences of this mechanism of action.
Martin Pall
__________________________________________________
On 2015-03-18 at 19:19, Martin
Blank wrote:
Andre,
Re your posting on a toxicology model, I am sending you the
abstract of a study showing interaction of EMF with particular groups in DNA to
initiate stress protein synthesis (i.e., initiation of the cellular response to
a harmful stimulus). One would expect interactions of EMF with many
cellular components, but this is the natural response of a cell, and the cell
is more sensitive to EMF than to temperature (heat shock).
Journal of Cellular Biochemistry 81:143-148 (2001)
Regulating Genes with Electromagnetic Response Elements
Hana Lin,1 Martin Blank,2 Karin Rossol-Haseroth,3 and Reba
Goodman1*
1Department of Pathology, Columbia University Health Sciences,
New York, NY 10032
2Department of Physiology,
3Department of Medicine,
Abstract A 900 base pair segment of the c-myc promoter,
containing eight nCTCTn sequences, is required for the induction of c-myc
expression by electromagnetic (EM) fields. Similarly, a 70 bp region of the
HSP70 promoter,
containing three nCTCTn sequences, is required for the induction
of HSP70 expression by EM fields. Removal of the 900 base pair segment of the
c-myc promoter eliminates the ability of EM fields to induce c-myc expression.
Similarly, removal of the 70 bp region of the HSP70 promoter, with its three
nCTCTn sequences, eliminates the response to EM fields. The nCTCTn sequences
apparently act as electromagnetic field response elements (EMRE). To test if
introducing EMREs imparts the ability to respond to applied EM fields, the 900
bp segment of the c-myc promoter (containing eight EMREs) was placed upstream
of CAT or luciferase reporter constructs that were otherwise unresponsive to EM
fields. EMREs-reporter constructs were transfected into HeLa cells and exposed
to 8 mT 60Hz ®elds. Protein extracts from EM field-exposed transfectants had
significant increases in activity of both CAT and luciferase, compared with
identical transfectants that were sham-exposed. Transfectants with CAT or
luciferase constructs lacking EMREs remained unresponsive to EM fields, i.e.,
there was no increase in either CAT or luciferase activity. These data support
the idea that EMREs can be used as switches to regulate exogenously introduced
genes in gene therapy. J. Cell. Biochem. 81:143-148, 2001. ß 2001 Wiley-Liss,
Inc.
Key words: electromagnetic field response elements; gene therapy
Low frequency electromagnetic (EM) fields induce increased
expression of the stress response gene HSP70 [Lin et al., 1997; Goodman and
Blank, 1998]. There are several parallels in the biochemical pathways induced
by EM fields and heat shock, but there are striking differences as well. Both
pathways involve the binding of heat shock factor 1 (HSF1) to a heat shock
element (HSE), but regulation of HSP70 gene expression byEM®elds requires three
nCTCTn binding sites in the HSP70 promoter that lie between ÿ230 and ÿ160,
upstream from the transcription initiation site. These three nCTCTn sequences
appear to act as electromagnetic field response elements (EMREs), since the
ability of an EM ®eld to induce stress proteins gradually gradually disappears
as the EMREs are mutated one by one [Lin et al., 1998a, 1999]. Removal of EMREs
by mutation does not affect the response to heat shock, since the heat shock
domain is downstream from the EM ®eld domain in the HSP70 promoter (between
ÿ106 and ÿ67) [Lin et al., 1997, 1998b, 1999].
__________________________________________________
On 2015-03-20 à 08:13, Dariusz
Leszczynski wrote :
André and others,
I certainly and fully agree with Martin Blank when he states
that stress response is activated by EMF and, especially, when he states “One
would expect interactions of EMF with many cellular components”. Absolutely so.
There might be many targets for interaction with EMF and Martin Blank speaks
from experience of doing research in EMF area.
I absolutely disagree with what Martin Pall is saying. Calcium
channels might be a target but it is not proven yet. Especially not proven that
it takes place in human body. However, Martin Pall writes as if it would be a
sure thing when he says “Fortunately, EMF action is much simpler. The
sole target of EMFs is the voltage sensor of the voltage regulated ion channels
including especially the calcium channels.” Especially his statement about “The
sole target of EMFs” is not justified by any scientific data.
Martin Pall is speaking as if he would be a student that found
something “new” and thinks that it is an “epicenter of everything”. I would
expect somewhat more balanced scientific opinion from retired professor and not
outburst like “So we have solved this problem and it is time to move on to the
many biological consequences of this mechanism of action”. This is not correct.
But this might be no wonder. Marin Pall did not do any research in EMF area.
He did not publish any studies on EMF effects. He also did not do any research
in area of calcium channels. Therefore, his claims of expertise are dubious…
What is even more concerning, is that Martin Pall goes around
and speaks such unbalanced opinions to other scientists, like e.g. two lectures
in Finland last week, and as expert witness in hearings before politicians and
decision-makers. Any scientist, really experienced in the area of EMF research,
will dismiss Martin Pall’s “sole target” claims easily. Using such out of
balance opinions, e.g. as expert testimonials, might be unwise as these
opinions will be easily dismissed, and rightly!
There are several potential mechanisms and all of them are to
some degree plausible. Research needs to validate them and prove that they take
place in human body, not just in cells grown in laboratory.
Best wishes,
Dariusz
__________________________________________________
"Pall, Martin L"
Objet: RE: Calcium channels are the main,
possibly the sole target for EMFs
Date: March 21 2015
05:46:46 UTC−4
Dariusz Leszinski seems to have forgotten that science is not a
matter of unsupported opinion, but rather of what the evidence shows. He
was present at one of my presentations in Finland last week and failed to raise
any questions about the presentation, despite having ample opportunity to do
so. There was widespread agreement among the other scientists present on
the strong support for the view that EMFs act via VGCC activation.
We now have the following types of evidence, each of which
provides strong support for VGCC activation, with the calcium channel blocker
studies alone providing compelling evidence. These include the following:
There are 26 different studies showing that calcium channel
blockers, agents specific for blocking the VGCCs, block or greatly lower all
effects of EMF exposure that were measured in each study. These include 5
classes of calcium channel blockers, with each acting of different sites and
having different structural properties. Each of these are thought to be
highly specific agents and we have, therefore, no alternative interpretation to
these results - the EMFs are activating the VGCCs.
The VGCCs and other voltage-gated ion channels have voltage
sensors located in the plasma membranes of cells, which based in their location
and structural properties, are predicted based on the physics to be exquisitely
sensitive to activation by these EMFs.
There is published evidence that pulsed microwave exposures
produce an almost instantaneous increase in intracellular calcium levels,
strongly supporting a direct activation of the VGCCs by these EMFs, as
suggested in the previous paragraph.
The VGCCs have been shown to have a universal or near-universal
role in converting electrical effects into chemical changes in cells, so it
should not be surprising that there appears to be a universal or near-universal
role of the VGCCs in producing biological responses to EMFs.
There are extensive published studies (close to 1000) showing
changes calcium fluxes and/or calcium signaling following microwave frequency
exposures with each of these, including the calcium efflux studies, providing
support for the VGCC activation mechanism.
There are a wide range of repeatedly reported responses to
microwave EMF exposures that can be explained as being caused by downstream
effects of VGCC activation and consequent increases in intracellular calcium,
including:
Oxidative stress, single strand and double strand breaks in
cellular DNA, other genotoxic responses including increases in 8-nitroguanine
and 8-oxoguanine, cancer, cardiac effects including tachycardia, bradycardia,
arrhythmia, possibly leading to sudden cardiac death, widespread
neuropsychiatric effects, male and female infertility and low levels of
melatonin. Many of these effects have been shown to be produced by
excessive activity of the VGCCs in humans, based on genetic studies.
Microwave EMFs act in plants act very similarly to the way they
act in animals, activating voltage regulated calcium channels and producing
large increases in calcium signaling responses. The plant responses are
also blocked by calcium channel blockers, including some the same blockers that
work in animals. The plant calcium channels have voltage sensors with
similar properties to the VGCCs in animals, thus providing an explanation for
the exquisite sensitivity of the plant channels to these fields.
It should be obvious, that the calcium channel blocker studies
provide the key piece of evidence pointing directly to the VGCCs (and plant
channels) as the targets of these fields, but the other types of evidence
provide powerful and extensive support for this conclusion from various types
of diverse evidence.
Science is and always has been a matter of evidence, preferably
evidence that examine a theory from a variety of different perspectives, such
that it can be tested not just from one perspective, but from many. It is
not and never has been based on unsupported opinion, Dr. Leszczynski.
Martin
Pall
__________________________________________________
On 2015-03-21 à 09:08, D L Henshaw a écrit :
Andre
Re: Exchanges between Daruisz and Martin Pall
I am very confused by these exchanges, so I have one question I
would like to ask and then to make a simple point.
Martin have you actually said: "The sole target of EMFs is
the voltage sensor of the voltage regulated ion channels including especially
the calcium channels." ?
If so, the claim of "sole target" in the context of
the interaction of magnetic fields with biological systems is clearly not
correct.
I refer of course to the near-explosion of research in recent
years into animal magneto-reception and navigation in the Earth's static
magnetic field. If I may remind you, evidence suggests exquisite MF sensitivity
to MF changes - some would say as low as 10 nT, but not to overstate it, let's
say below 50 nt. To name just three areas, such sensitivity includes animal
orientation, navigation and effects on pain threshold.
In the field of animal magnetoreception, two primary
MF interaction mechanisms are well-discussed: (i) magnetic particles in the
body and (ii) the ability of low intensity MFs to alter chemical reaction
pathways by operating on the spin states of pairs of radicals - the so-called
Radical Pair Mechanism. This mechanism is deemed to take place in cryptochrome
protein molecules in the eye, functioning as the magnetic compass in birds and
other species.
Whether ion channels are part of the process of magnetoreception
downstream of magnetic particle and/or RPM interactions is a
separate question.
I cite no references here. There are many, those interested may
do a Google search
Regards
Denis Henshaw
By all means circulate these comments
__________________________________________________
Le 2015-03-21 à 23:43, Henry Lai a écrit :
Hi André,
Please forward the following to the other people of concern,
Marty and Dariusz, etc. Thanks.
Henry Lai
-----------
I agree with Marty Pall that “calcium channels” is an important
topic of investigation on the mechanisms of EMF bio-effects. But, I am not sure
that “calcium channels” is the “sole” answer to the mechanism of EMF
interaction with living materials. The idea that EMF (particularly ELF
EMF) affects calcium channels is not new. But, there are some concerns on how
big a role it plays.
1
It is quite difficult to envision how alternating EMF affects
calcium channels. The channels are activated when membrane potential
depolarizes. That means the change that triggers the effect is spatially
directional, i.e., the outer part of the cell membrane becomes “less positive”
and a cell in question has to be aligned in a certain orientation with the
detection of the EMF. This may be true in in vitro experiment,
but not in in vivo experiments and “human exposure situations”
when an animal (human) moves in the field.
2
Temporally, it is difficult to understand how oscillating EMF
affects calcium channels. The time period of change when exposed to an AC-field
in the environment is probably too fast for the channels to detect, for ELF
field and particularly for RF field. One has to consider that RFR may exert its
effect by its low-frequency modulation-component and not the carrier frequency
(see the study by Ross Adey on calcium efflux). If this was true, one would
expect that modulated-RFR should be more potent that continuous-wave RFR of the
same frequency and SAR. The literature does not support this.
3
In 1992, Liburdy published a study (which I consider to be an
ingenious experimental design and concept) showing that ELF-EMF affected
calcium channels by “induced current” (or electric field, and not magnetic
field). What it means is that to show effect on calcium channels, one has to
use very low-frequency fields (< 10 Hz) and/or high intensity. In most of
the recent studies on calcium channels, relatively high fields were used (1-10
mT). How could the results from “calcium channels” explain the epidemiological
effects of increased cancer risk at 0.4 uT?
4
How can “power intensity” and “frequency window” effects be
explained by the assumption that EMF affects calcium channels?
5
It is quite puzzling that most of the effects reported have been
on the L-form of calcium channels. However, there are reports showing that ELF
EMF inhibited the T-form. And, ELF had no significant effect on the N-form, but
RFR activated it. If change in membrane polarization by EMF is the cause,
should one expect similar effects on all forms of calcium channel? Do they use
the same positively-charged polypeptide domain to open the channel?
6.
How does “cyclotron resonance” fit into this? There are
many reports on calcium cyclotron resonance and EMF (probably as many as the
“calcium antagonist” studies.) Much lower field intensity is needed for the
cyclotron resonance effect (and 7 Hz).
In general, I think it is not a good idea to make very definite
conclusion on scientific matters as stated in the title of André’s e-mail:
“Calcium channels are the main, possibly the sole target for EMFs”. As Einstein
said, “who can be so sure about nature?”, particularly, for scientists.
Best,
Henry Lai
__________________________________________________
From: "Dariusz Leszczynski"
Objet: RE: Martin Pall responds to Dariusz Leszinski
Date: 22 mars 2015 13:34:38 UTC−4
À: 'André Fauteux' , "'Henry
Lai'"
André,
Here is my response to Marin Pall and Henry Lai and others…
Please, pass it along to all interested…
Best,
Dariusz
PS In your subject line, my surname is misspelled – it should be
Leszczynski
************
Henry Lai explained in detail what the problem is, with
statements made by Martin Pall. In comparison with me, Henry was more
elaborate, I was very brief… but the conclusion is similar – do not jump to
premature conclusions about biological systems, as Martin Pall does.
I remain unconvinced by the below seen response of Martin Pall
to my message and I stick firmly to what I said before. I am now highlighting
some fragments of my earlier e-mail using red bold fonts, to make sure that my
points are understood and not misunderstood.
In my earlier message, responding to Martin Pall claims (seen
towards the bottom of this e-mail chain), I said as follows:
“…I certainly and fully agree with Martin Blank when he
states that stress response is activated by EMF and, especially, when he
states “One would expect interactions of EMF with many cellular components”.
Absolutely so. There might be many targets for interaction with EMF and
Martin Blank speaks from experience of doing research in EMF area.
I absolutely disagree with what Martin Pall is saying. Calcium
channels might be a target but it is not proven yet. Especially not
proven that it takes place in human body. However, Martin Pall writes as if it
would be a sure thing when he says “Fortunately, EMF action is much
simpler. The sole target of EMFs is the voltage sensor of the voltage
regulated ion channels including especially the calcium channels.” Especially
his statement about “The sole target of EMFs” is not justified by any
scientific data.
Martin Pall is speaking as if he would be a student that found
something “new” and thinks that it is an “epicenter of everything”. I would
expect somewhat more balanced scientific opinion from retired professor and not
outburst like “So we have solved this problem and it is time to move on to the
many biological consequences of this mechanism of action”. This is not
correct. But this might be no wonder. Marin Pall did not do any
research in EMF area. He did not publish any studies on EMF effects. He also
did not do any research in area of calcium channels. Therefore, his claims
of expertise are dubious…
What is even more concerning, is that Martin Pall goes around
and speaks such unbalanced opinions to other scientists, like e.g. two lectures
in Finland last week, and as expert witness in hearings before politicians and
decision-makers. Any scientist, really experienced in the area of EMF
research, will dismiss Martin Pall’s “sole target” claims easily. Using such
out of balance opinions, e.g. as expert testimonials, might be unwise as these
opinions will be easily dismissed, and rightly!
There are several potential mechanisms and all of them are to
some degree plausible. Research needs to validate them and prove that they take
place in human body, not just in cells grown in laboratory…”
I also fully agree with Henry Lai that explaining the “sole
target” as calcium channels might be difficult, based on our current knowledge.
Table of the “26 studies” referred by Martin Pall and published
in his article in 2013 (attached) shows his inexperience in EMF research. Table
is a mixed-bag of all possible electromagnetic fields (see column 2) and it
fits well with what Henry Lai is saying – difficult to imagine how the calcium
channel would be affected and how important it might be as mechanism…
As Henry Lai wisely quoted Einstein: “who can be so sure about
nature?” As H
I consider the statements, by Martin Pall concerning, calcium
channels and EMF as the sole mechanism for all of the EMF types (sic!) as
mostly unfounded and misleading and his expertise in EMF research as
insufficient for providing expert testimonials.
Best wishes,
Dariusz
__________________________________________________
From: "Dimitris Panagopoulos"
Object: Rép : Dariusz Leszczynski responds to Martin Pall
Date: March 22 2015 20:18:13 UTC−4
À: André Fauteux
Cc: "DEBORAH RUBIN"
Attached is a biophysical mechanism (Panagopoulos et
al 2000; 2002) in very good agreement with what Dr Pall says....Irregular
gating of electrosensitive channels on plasma membranes by EMFs is
a most plausible direct mechanism. The rest effects like stress
response, DNA damage, etc, are secondary effects.
It is shown by physics and molecular data that the lower
frequency fields (ELF) and the pulsed fields are more bioactive, which explains
many observed effects. A key point is that all man-made EMFs are polarized
in contarst to natural ones. Polarized oscillating EMFs induce parallel
forced-oscillations in all charged molecules in biological tissue, especially
in the mobile ions. The combined polarized (parallel and in phase) movement of
several ions in the vicinity of the voltage-sensors of an electrosensitive
channel, exerts combined forces that cause the irregular opening or closing of
the channel. This causes alteration in the physiological ion
concentrations within the cell, which initiates secondary effects that Dr
Pall very well describes in his papers, and which finally disrupt cell function.
The above biophysical mechanism seems to be the only one
which is verified by numerical test in computer (Halgamuge 2011).
Thanks
Dimitris J. Panagopoulos
__________________________________________________
De: Igor Beliaev
Objet: Rép : Dimitris Panagopoulos: Irregular gating of
electrosensitive channels on plasma membranes by EMFs is a most plausible
direct mechanism
Date: 23 mars 2015 07:46:32 UTC−4
À: André Fauteux
Dear Andre and All,
To my knowledge, membrane/ion channels biophysical
mechanisms have been considered for long time, since studies by H. Frohlich and
F. Kaiser. Please, see my recent review on the RF biophysical mechanisms in the
attachment. Some of the membrane/ion channels mechanisms as well as other
mechanisms were numerically tested. See for example studies by F. Srobar and V.
Binhi. However, numerical tests cannot be considered as a final prove of
mechanism. Particularly because some parameters are usually defined for the
numerical calculations and the outcome is sensitive to these definitions.
Although RF may affect coherent behavior of membranes/ion channels, our studies
show that DNA is a target for resonance interaction of RF with leaving cells
(see in attachment).
Best regards,
Igor
Igor Belyaev, Dr.Sc.
Head, Laboratory of Radiobiology
Cancer Research Institute
Slovak Academy of Science
Vlárska 7, 833 91 Bratislava
Slovak Republic
From: Martin Blank
Object: Rép : California knew smart meters were dangerous (url of my English summary)
Date: Aprl 1 2015 01:09:20 UTC−4
Response to Martin Pall’s March 26 email
From: Martin Blank
Object: Rép : California knew smart meters were dangerous (url of my English summary)
Date: Aprl 1 2015 01:09:20 UTC−4
Response to Martin Pall’s March 26 email
Martin Pall’s March 26 email provided many examples of the effect of EMF on Ca-transporting systems. However, the question is whether one can designate this as the initial interaction of EMF with cells that initiates a chain of reactions. After all, EMF interacts with many cellular systems, and judging from the earlier studies of Lai and Singh (Int. J. Radiat. Biol. 69:513–521, 1996), one would certainly expect interactions with the DNA in cells.Goodman and Blank (Adv in Chemistry 250:423-436, 1995; Cell Stress & Chaperones 3:79-88, 1998) showed EMF interaction with DNA to initiate the cellular stress response and synthesis of stress protein hsp70. They also identified a combination of DNA bases that EMF interacts with, suggesting that there are bound to be many places on the two meter long molecule that have this combination and can interact (Lin, Blank, Rossol-Haseroth and Goodman, J Cell Biochem 81:143-148, 2001). Because of the extensive coiling of DNA needed to enable the molecule to fit into the nucleus, there are coils of many sizes. The coiling of DNA provides a structural basis for why DNA acts as a fractal antenna (Blank and Goodman, Internat. J. Radiation Biol 87: 409-15, 2011). The different size coils in the DNA interact with different EMF wave lengths.The DNA research has important practical implications:· * The cellular stress response is the cell’s reaction to a variety of potentially harmful stimuli (e.g., changes in temperature, pH, etc.), and indicates that EMF is a potentially harmful stimulus according to the biological criterion.· * The threshold for response to EMF is lower than for changes in temperature, i.e., ‘heat shock’. This shows that the ‘thermal criterion’ for judging EMF safety for cells is incorrect according to the ‘biological criterion’.· * This also shows that despite the claims of regulatory agencies, there is a recognized cell-EMF interaction mechanism.· * It is important for regulatory agencies considering EMF safety issues to include biologists who are familiar with relevant cell biology research.
De: "Pall, Martin L"
Objet: RE: Response to Martin Blank’s April 1 emailDate: 4 avril 2015 21:07:33 UTC−4À: André FauteuxDear Martin Blank:Thank you for your thoughtful and substantive response to my earlier message - it is much appreciated and I have spent considerable time going over the relevant papers. Let me reiterate that the question I am raising is whether VGCC activation and downstream effects produced by such activation can explain the important experimental results that you have obtained - or not. I have posted that the activation of the heat shock transcription factor can be produced by excessive intracellular calcium levels and that this response to [Ca2+]i has been found in diverse eukaryotic organisms including diverse animals (including Drosophila and Ceanorhabditis and both vertebrates and other invertebrates) , higher plants and in yeast. What you show is that the stress response you have been studying is produced in part via heat shock transcription factor activation and in part via other mechanisms. What you also show is that you have a plausible mechanism based on the direct interaction of EMFs with DNA which may explain, at least in part, your studies. The question is whether this plausible mechanism is fundamentally correct.You have evidence that several other transcription factors are activated EMF exposures, notably Ap-1, Ap-2, and Sp-1. Ap-1 is, of course, well known to be activated by oxidants and therefore, may be expected to be activated by the peroxynitrite/free radical/oxidative stress pathway that is an important downstream pathway of VGCC activation and consequent elevation of [Ca2+]i. I don't know enough about Ap-2 and Sp-1 to comment on them. Calcium, of course has important roles in transcriptional regulation and activation of the L-type VGCCs was shown to have a direct important role in transcriptional regulation as well, a role in addition to its role in increasing [Ca2+]i (see Dolmetsch et al, Science 2001;294(5541):333-339). Other possible effects that are downstream of VGCC activation involves the known role of elevated peroxynitrite, acting through its free radical breakdown products, in producing both single strand and double strand breaks in DNA, a mechanism discussed in my 2013 EMF paper. That paper also discusses an important flaw in the Friedman paper which concluded that NADH oxidase was the source of oxidants following EMF exposure - the "specific" NADH oxidase inhibitor is, in fact not specific, but rather is also an ion channel blocker, raising the question of whether peroxynitrite is the main source of oxidants following exposures, rather than NADH oxidase. One of the consequences of DNA strand breaks is that they produce a major activation of poly-ADP-ribosylation of chromosomal proteins which can both have major effects on chromosome and therefore DNA structure and can also lead to a depletion of NAD/NADH pools, with the NADH effect, leading to greatly lowered energy metabolism. All of these things can produce major stresses on the cell, and therefore in principle, each could have a role in the stress response that you have been studying.The 5 calcium channel blockers that have been used in the VGCC studies each act on different sites and are each thought to be highly specific of VGCC blockage, although they are each specific for one of 4 different families of VGCCs. So we have strong evidence for a causal role of the VGCCs in responding to the fields. We also have the Pilla 2012 study which showed that the VGCCs are activated almost instantaneously by the EMFs, producing an almost instantaneous increase in calcium/calmodulin-dependent NO synthesis. And we know that the VGCCs and the other voltage-gated ion channels each have a voltage sensor which I have argued is exquisitely sensitive to EMFs - and the voltage sensor of the VGCCs has a universal or near universal role in converting electrical effects into chemical changes in the cell. I am going to email you directly a paper that considers many of these issues including the voltage sensor properties.It seems to me that we each have a plausible set of mechanisms leading to the stress response you are studying - so my question for you is whether you see any definitive evidence that DNA is the EMF target leading to those stress responses?One other thing, I think that your last section in the DNA fractals paper, on implications for safety standards, is absolutely bang on. The safety standards are off by orders of magnitude from where they need to be. Whatever differences we may have on the issue of mechanism should not detract from our fundamental agreement that the ICNIRP and other safety standards are without scientific merit.Martin Pall
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