Ion Channels, EMF and RF Radiation, Tissue types and Cancer, the links. By Dr Chris Barnes, Bangor Scientific and Educational Consultants, Bangor, Gwynedd, Wales, e-mail firstname.lastname@example.org
The common denominator which accounts for the above apparent dichotomy of ELF/modulated RF presenting sometimes as a carcinogen and sometimes as a promoter is undoubtedly the presence of ion channels and moreover their specific type and distribution of expression. For RF to act as a carcinogen, the balance of available evidence suggests that the carcinogenesis must take place in a tissue wherein ion channels are normally and widely expressed from the start. In brain tissue GSM modulation is shown to disturb calcium and serine transport via ICR leading to malignant transformation. Normal liver and lung tissue are known to have potassium channels, see above. Verizon CDMA mobile phone signal stimulates potassium ICR extremely close to the first sub-harmonic. AM Radio transmission is confirmed to be a Leukemia risk in association with ICR disruption of potassium metabolism. Previous observation of childhood leukemia in association with 50 Hz fields in the UK and with 60 Hz fields in the USA are shown to be due especially to strong ICR effects in potassium channels. Analysis of UK TV transmitter modulation as used in the 1970’s and 1980’s ( Dolk studies) not stimulate any significant ICR harmonics of Potassium hence accounting for the insignificance of their result. Finally UK TETRA emissions are confirmed not to be a cancer risk on the same basis..
Although human kind has been exposed to both ELF EMF (50/60 Hz) and RF radiation (radio broadcasts and the like) since the 1920’s concern as to RF safety has mainly grown since the advent of mobile phone communications and wifi for all.
Studies on RF and EMF safety have taken 3 main forms, these are; animal studies, cell culture studies and human population epidemiology studies.
On balance just over half of the animal studies and cell culture studies flag up some sort of a problem. Several research groups note changes in calcium efflux in brain tissue. others note DNA changes. Epidemiological studies usually note associations with brain and haemopoietic cancers (refs).
The present author has noticed associations with other types of cancer as well (refs). Moreover, the present author has also shown that although the epidemiological studies of Dolk (1997) produce inconclusive results, it is possible to reconcile such apparent differences if a) RF radiation is regarded rather as a cancer promoter than an initiator and b) if levels of atmospheric pollution at and around each transmitter site are taken into account. There is some support for the notion that TV emissions are more potent than mixed emissions or FM only emissions and this is line with the earlier work and suggestion of Morton and Phillips 1983. In respect of RF as a cancer promoter, I have previously pointed out the ‘p53’ link, big risk for some small for others. In other words, my observation was that in individuals with a faulty tumor suppressor gene exposure to an unknown carcinogen together with RF as the promoter could be very dangerous whereas for others nature would make the necessary repairs and neoplastic transformation would not occur (refs). I have also commented on how growing use of RF technologies may be causing and apparent fall in cancer latency periods. ( refs).
Directly contrary to the notion of RF as a cancer promoter, others have provided, very recently indeed, using rodent studies that it may be a cancer initiator or carcinogen, US Department of Health NTP observation (2018 rodent study)
Findings of the NPT study at 900 MHz: AT&T and T-Mobile use GSM frequencies are that there was some evidence linking RFR with malignant schwannoma in the hearts of male rats, no evidence for same in female rats. Equivocal evidence linking exposure to malignant brain glioma in females. Other tumors of various types in both sexes “may have been related to cell phone RFR exposure,”. Less serious “nonneoplastic lesions” were more frequent in exposed males and females.
Findings At 1900 MHz: Sprint, Verizon, and US Cellular use CDMA frequencies
Equivocal evidence of carcinogenicity in lung, liver and other organ tissues in both male and female mice.
I shall spend the rest of this paper explaining and reconciling the link between RF as a carcinogenic and RF as a promoter.
Tissue type, Ion Channels and RF/EMF a promoter, a carcinogen or both?
It is well known that high level RF radiation could interact with biology. With thermal interaction, the displacement current is sufficient to cause ohmic heating not compensated for by the counter-cooling effect of blood flow and this heating directly causes burning, scarring and tissue damage. High levels of pulsed electric field are also sufficient to cause cell membrane insulation breakdown by so called electro-proration. The latter has been used as a technique for fusing cells.
Less known are the effects of athermal electromagnetic radiation when the cooling exceeds the SAR or specific absorption rate. There are several hypotheses including for instance frequency locking of polaron or soliton modes, rectification of the electric field component by ion channels and over ions by purely forced vibration and magnetic influence over ion currents by either Lorentz force or cyclotron resonance. There is evidence of soliton modes in proteins in biological systems but the interaction frequencies are many orders of magnitude higher than those used in radio communication and mobile telephony. Theoretical considerations suggest that it is far easier for the magnetic field of an ELF EMF or modulated RF signal to perturb ions in a channel than it is for the electric field.
Weak sinusoidal electric fields modify the calcium efflux from freshly isolated chick and cat cerebral tissues bathed in Ringer's solution, at 36 degrees, see Bawin and Adey (1976).
Experimental evidence for the perturbation of calcium ions by such fields exists, see for example CF BlEffects of ELF (1–120 Hz) and modulated (50 Hz) RF fields on the efflux of calcium ions from brain tissue in vitro
C. F. Blackman S. G. Benane D. E. House W. T. Joinesackman, SG Benane, LS Kinney, WT Joines… - Radiation …, 1982 - rrjournal.org. and Effects of ELF (1–120 Hz) and modulated (50 Hz) RF fields on the efflux of calcium ions from brain tissue in vitroC. F. Blackman S. G. Benane D. E. House and W. T. Joines (1995).
Experimental evidence for calcium ion perturbation has been shown by Smith et al using diatoms ‘Calcium cyclotron resonance and diatom mobility’ (1987).
Tenford (1991) reviews both experimental evidence and theoretical models which relate pericellular currents and electrochemical events at the outer membrane surface to transmembrane signaling pathways and cytoplasmic responses. Biological responses to ELF fields at the tissue, cellular and molecular levels are summarized, including new evidence that ELF field exposure produces alterations in messenger RNA synthesis, gene expression and the cytoplasmic concentrations of specific proteins.
The common denominator which accounts for the above apparent dichotomy of ELF/modulated RF presenting sometimes as a carcinogen and sometimes as a promoter is undoubtedly the presence of ion channels and moreover their specific type and distribution of expression. For RF to act as a carcinogen, the balance of available evidence suggests that the carcinogenesis must tale place in a tissue wherein ion channels are normally and widely expressed from the start.
So let us consider and reiterate the findings of the NPT study at 900 MHz: AT&T and T-Mobile use GSM frequencies which was that there was some evidence linking RFR with malignant schwannoma in the hearts of male rats, no evidence for same in female rats. Equivocal evidence linking exposure to malignant brain glioma in females. Other tumors of various types in both sexes “may have been related to cell phone RFR exposure,”. Less serious “nonneoplastic lesions” were more frequent in exposed males and females.
The common dominator in heart and brain tissues is that they are both excitable tissues where sodium, potassium, calcium and chloride channels are normally expressed. All that is required is that an ELF EMF or a modulation frequency in an RF source disturbs one or more of these channels for a sizeable part of the cell cycle and on a regular basis and serious dysregulation of cellular processes, including the possibility of malignant transformation can happen.
Next I consider and re-iterate the findings of the same study at 1900 MHz using Sprint, Verizon, and US Cellular CDMA frequencies where there was found equivocal evidence of carcinogenicity in lung, liver and other organ tissues in both male and female mice.
Once again, the common dominator is ion channels. Voltage gated potassium channels associated with the KCND2 (HGNC Symbol) gene are expressed in normal lung and liver tissue, see http://www.proteinatlas.org/ENSG00000184408-KCND2/tissue
Voltage-gated potassium (Kv) channels represent the most complex class of voltage-gated ion channels from both functional and structural standpoints. Their diverse functions include regulating neurotransmitter release, heart rate, insulin secretion, neuronal excitability, epithelial electrolyte transport, smooth muscle contraction, and cell volume. Four sequence-related potassium channel genes - shaker, shaw, shab, and shal - have been identified in Drosophila, and each has been shown to have human homolog(s). This gene encodes a member of the potassium channel, voltage-gated, shal-related subfamily, members of which form voltage-activated A-type potassium ion channels and are prominent in the repolarization phase of the action potential. This member mediates a rapidly inactivating, A-type outward potassium current which is not under the control of the N terminus as it is in Shaker channels.
Voltage-gated H+ channels are known to be present in alveolar epithelial cells but their purpose is not fully understood.
Once again, I propose that all that is required is that an ELF EMF or a modulation frequency in an RF source disturbs one or more of these channels for a sizeable part of the cell cycle and on a regular basis and serious dysregulation of cellular processes, including the possibility of malignant transformation can happen.
So what of tissue that has already gone malignant transformation and commenced metastasis. It is known from multiple sources (refs) that ion channels and also mutated isoforms of the same are aberrantly expressed in multiple types of cancer tissue (refs). Moreover, that different ions channels are active as inwardly or outwardly rectifying at different parts of the cell cycle.
Hence I postulate that ELF EMF and/or modulated RF with appropriate modulation frequencies could enhance activity in appropriate channels within metastasizing tissues and hence speed metastasis. This not only and elegantly explains the observation I have made previously of RF as a cancer promoter (ref) but also explains the observation of apparently reducing latency periods for a number of common cancers.
Specific cases, which ions are involved and do they match with both the cancer type and the earth geomagnetic field at the place of observation?
The accepted mechanism for EMF or modulated RF interference with the flow of ions in a channel is one of Ion Cyclotron Resonance (ICR) (refs). Although there are objections as to the precise physics and physical chemistry of the process in terms of ion damping and mean free path and various modifications to the theory have been suggested such as the Ion Parametric Resonance Model (IPR) of Lednev, the essential resonance frequency calculation always is of a similar form and always involves the value of the earth’s geomagnetic field. ICR in biology has been tested experimentally using the propulsive motion of diatoms.
Basically in ICR the EMF causes ions at the membrane surface to break free and engage in a helical path suited to entry into or exit from a similarly shaped ion channel.
Case 1: The NPT study.
It is believed the NPT study took place in North Carolina. The average geomagnetic field there is some 52 micro-Tesla.
First I will consider a 900 or 1800 MHz GSM signal. There are major modulation components at 217 Hz and 8.3 Hz. It is known that harmonics of IPR frequencies also stimulate IPR.
It can be seen that the Ca 3rd ICR harmonic is active and also the Serine transporter is disturbed at the fundamental ICR frequency.
Both calcium and serine transport are crucial in properly functioning brain tissue and disturbance will lead to several problems.
An increase in the concentration of free calcium ions during metaphase appears to stimulate the onset of anaphase. Such an increase, regulated by the cell itself, may contribute to the initiation of chromosome separation in mammalian cells.
Mismatch between the external time and the internal circadian time causes loss of circadian organization and is frequently linked to cancer, see Kiessling and Cermakian 2017. Thus exposure to GSM 10 minutes on , 10 minutes off for 9 hours per day as in the NPT study would do just this.
D-serine fulfills criteria for defining its functionality as a neurotransmitter and challenges the dogma relating to neurotransmission, for it is the “unnatural” isomeric form of an amino acid and interestingly it is derived from glia rather than neurons.
Hyashi et al (1997) suggest that C6 glioma cells may accumulate d- and l-serine through a common ASCT-like transporter and provide a useful model for the glial uptake of extracellular d- and l-serine in the brain.
Verizon CDMA produces a band of modulation as a pseudo random comb 2-16 Hz with peaks at 2Hz intervals. The calculated ICR harmonics and sub-harmonics for various ions at 52uT and at Verizon CDMA modulation frequencies are shown in Table 2 below:
Numerous ion channels and amino acid transporter channels are seen to be disturbed. Normal liver and lung tissue are known to have potassium channels, see above. The data, table 2, shows that Verizon CDMA mobile phone signal stimulates potassium ICR extremely close to the first sub-harmonic.
Saier et al (1988) discusses the ‘Neutral amino acid transport systems in animal cells: Potential targets of oncogene action and regulators of cellular growth’. Clearly the Verizon modulation disturbs transport of 4 essential amino acids and here we have a probable mechanism of oncogene induction and malignant transformation.
Case 2 AM Radio Transmitters South Korea Ha et al (2007)
The odds ratio for all types of leukemia was 2.15 (95% confidence interval (CI): 1.00, 4.67) among children who resided within 2 km of the nearest AM radio transmitter as compared with those resided more than 20 km from it. For total RFR exposure from all transmitters, odds ratios for lymphocytic leukemia were 1.39 (95% CI: 1.04, 1.86) and 1.59 (95% CI: 1.19, 2.11) for children in the second and third quartiles, respectively, versus the lowest quartile. Brain cancer and infantile cancer were not associated with AM RFR.
Case 3 AM Radio Transmitters Vatican City, Rome Italy.
The risk of childhood leukemia was higher than expected for the distance up to 6 km from the radio station (standardized incidence rate = 2.2, 95% confidence interval: 1.0, 4.1), and there was a significant decline in risk with increasing distance both for male mortality (p = 0.03) and for childhood leukemia (p = 0.036).
Case 2 and Case 3 analysis
I shall analyze each case separately since ICR depends on the geomagnetic field as it differs in South Korea and Rome, being 50 micro-Tesla on average in the former location and 46 uT in the latter.
Regarding modulation frequencies, AM radio channels are separated by 9KHZ on the Medium and Longwave and by 5 KHZ on the Shortwaves. I thus expect two equal sidebands of 4.5 and 2.5 KHZ respectively, effectively an audio continuum. Clearly, I can’t analyze for all frequencies so I will be forced to make certain assumptions. Assuming music transmission I assume a peak at half the passband so I will analyze for a modulation frequency of 2.25 and 1.25 KHz respectively. When voice modulation is used I will take the bandwidth limits and the average peak frequencies for the average male and female voice thus I will analyze for the following modulation frequencies which are: 85 Hz, 165 Hz, 180 Hz, 255 Hz and 125 Hz.
Case 2 Analysis Data Table : see below
Case 3 Analysis data table: see below
On the basis that excess Leukemia cases are found in both South Korea and Rome Italy with virtually the same odds ratio, I have decided to treat the data by seeking commonalities in the ions and amino acid transporters in each case. Firstly I dismiss HP042- because I have unpublished data which suggests that higher order ICR harmonics are associated with channel blocking rather than enhancement. In this respect we see enhancement in case 2 and blocking in case 3. I further dismiss bicarbonate and proton because they are only found in case 2 and not case 3. Although there is much debate about the significance of Lithium as a biological ion, it is nevertheless present in biological systems in trace amounts thus I will include it in my analysis especially as the second harmonic of its ICR appears to be closely stimulated in case 2 and the fundamental in case 3. Lithium enhances growth of human leukaemia cells in vitro, see Gauwerky and Golde (1982). Likewise I will include hydroxyl as low harmonics of ICR are present in both cases. I will dismiss magnesium as it is only present in case 2. I will include Calcium as it is present in the 19th harmonic in case 2 and the 2nd harmonic in case 3. I will reserve zinc until the discussion section. I will include Chloride because high harmonics of ICR are present in each case. I regard Potassium as extremely significant and will include as the 13th harmonic of ICR is present in case 2 and the 10th harmonic in case 3. HERG potassium channels are constitutively expressed in primary human acute myeloid leukemias and regulate cell proliferation of normal and leukemic hemopoietic progenitors, see Pillozzi et al (2002). They report that Herg is switched off in normal peripheral blood mononuclear cells (PBMNC) as well as in circulating CD34+ cells, however, it is rapidly turned on in the latter upon induction of the mitotic cycle. Moreover, hergappears to be constitutively activated in leukemic cell lines as well as in the majority of circulating blasts from primary AML. It is my guess that ICR stimulation of potassium results in changed timing of the normal mitotic cycle ruuning counter to the effect of normal circadian clock genes. Moreover, TASK-3 Two-Pore Domain Potassium Channels have an important role in the Entrainment of Mammalian Circadian Rhythms, see Atkinson et al ( University of Kent) https://kar.kent.ac.uk/47952/. All potassium ions in all types of potassium channel within the organism will be stimulated at the same ICR frequency and hence we have here a second and parallel mechanism for Leukemic transition.
Moreover, considering amino acids it would appear the common denominators are Glutamine and histidine which appear to be potentially blocked and enhanced in each case so I envisage these effects may cancel out.
Case 4 50 HZ ELF EMF
Wolf et al (2004) exposed HL-60 leukemia cells, Rat-1 fibroblasts and WI-38 diploid fibroblasts to 50 Hz extremely low frequency electromagnetic fields and found enhancement of cell proliferation and DNA damage concluding possible involvement of a redox mechanism.
The results of Kabuto et al (2006) provided additional evidence that high MF exposure was associated with a higher risk of childhood leukemia, particularly of ALL. The odds ratios for children whose bedrooms had MF levels of 0.4 μT or higher compared with the reference category (MF levels below 0.1 μT) was 2.6 (95% CI = 0.76–8.6) for AML + ALL and 4.7 (1.15–19.0) for ALL only.
Case 4 Data Analysis Table Below:
In preparation of the above table I considered 50 Hz fields in the UK at 48 uT.
Modern power systems are especially harmonic rich due to solid state switching, renewable energy systems inverters and phase imbalance so I have included harmonics up to the 9th harmonic. Feychting and Allbom (1995) clearly unware of the implications of ICR state that there is no known mechanism by which magnetic fields of the type generated by high voltage power lines can play a role in cancer development yet nevertheless, epidemiologic research has rather consistently found associations between residential magnetic field exposure and cancer. This is most evident for leukemia in children.
In order to analyze the mechanism further I consider the commonalities of the effects of 50 HZ and its harmonics on ICR of various biological ions with those of modulated AM radio. I note that in line with AM radio, Lithium, Hydroxyl, and Potassium are affected. The amino acids Glutamine and Tyrosine also. I developed an argument above to show that potassium and lithium channels are the two involved in leukemic transformation and I would expect that the be the same here.
Abdallah et al (1987) have demonstrated for certain rodent tumors that modification of host nutritional status by restriction of the dietary intake of tyrosine and phenylalanine exerts a dramatic antimetastatic effect directed particularly on spontaneous hematogenous metastasis. I propose that here we have the counter effect in operation and that ICR is activating the tyrosine transporter so that more tyrosine kinase is synthesized. Tyrosine kinase inhibitors have anti- leukemic properties.
The ultimate test of these hypotheses is to see if they can account for the observation of childhood leukemia in the USA which has not only a different mains frequency of 60 Hz but also different geomagnetic field.
Case 5 60 Hz ELF EMF USA.
Case 5 Data Analysis Table Below:
Intriguingly we see that the self-same potassium ICR harmonics at 8,12 and 24 times the ICR fundamental frequency are hit is the USA as in the UK. This being purely by coincidental choice of their mains frequency and the higher geomagnetic field in North America.
Further testing of the hypothesis ought to be possible. I would expect to see no ICR potassium correlation in parts of the world where leukemia is minimal. Another test is to try and choose adjacent countries with the same or very closely related geomagnetic field values but different power frequencies. I have used to map below which shows world Leukemia deaths in order to assist.
The average gmf in West Africa is of the order of 33.75 micro-Tesla.
The Data Analysis Table for West Africa is shown below:
Although numerous ion and amino acid ICR harmonics are potentially stimulated, the dangerous potassium effect remains absent.
Magnesium and zinc are the elements having essential roles in regulation of cell growth, division and differentiation. There have been some studies in the literature suggesting an association between the deficiency of these elements and the development of malignant disorders. I postulate here that ICR stimulation of magnesium channels may actually be having a protective effect.
Case 6 The Dolk et al TV Transmitter’s paper
Dolk et al performed statistical analysis for a number of UK TV transmitters combined in the period 1974-1986, four overlapping groups of transmitters defined by their transmission characteristics, and for all transmitters separately. There were 3,305 adult leukemia cases from 0-10 km (observed/expected (O/E) ratio = 1.03, 95% confidence interval (CI).
This only represents a tiny increased excess risk. Of note, however, is the fact that this was the era in which analogue TV emission was still being used and as such every transmission would have contained an element of amplitude variation at the frame frequency of 25 Hz.
Case 7 Test Case: TETRA
Tetra emissions are now universal across Britain and are used for all user emergency services.
Modulation contains inter- alia amplitude pulses at .98Hz, 17.64Hz and circa 70 Hz.
The data Table for TETRA at UK GMF values is shown below
In two previous papers (refs) I have speculated that TETRA ought to be either safe or even anti-cancer!
From the data table it can be seen that Tetra emissions do stimulate directly or even closely any ICR harmonics with the exception of Zinc and Serine. In my paper on Quantum mechanical distance effects of transmitter masts, TETRA is shown only to be associated with 1 in 36 of the cancers considered.
As far as nutrients go Zinc is anti-cancer and serine is pro-cancer and I have hypothesized that ICR stimulation is tantamount to dietary increase, see above. Thus, in this specific case I expect the two effects to cancel.
It can be clearly seen that TETRA is not a threat to biology, at least in the UK and the result is entirely consistent with the threads developed above.
It has been shown that different cancers develop in different tissues specifically in accord with both the types of ion channel and/or amino acid transporter present before and after metastatic transformation and the ability of specific frequencies at ELF EMF or their counterparts modulated onto RF carrier waves to stimulate the Ion Cyclotron Resonance Frequencies or low to moderated harmonics of ions/amino acids capable of being conducted by those said channels.
This accounts fully for the observations made in the NPT rodent study.
This further accounts fully for the observation of childhood leukemia in association with 50 Hz fields in the UK and with 60 Hz fields in the USA due especially to strong ICR effects in potassium channels.
Further geographic distributions of Leukemia in counties with lower GMF can be accounted for.
The rather insignificant result of Dolk II on TV transmitters and cancer can also be accounted for.
Finally TETRA emissions are confirmed not to be a cancer risk on the same basis.
Previous work of others has focused purely on disturbed Calcium ICR as a vehicle in carcinogenesis. Here it is shown that disturbance of Potassium and certain amino acids ICR are also important whereas disturbance of those of magnesium and zinc in some cases might even be protective.