Genetic effects of non-ionizing electromagnetic fields
Henry Lai. Genetic effects of non-ionizing electromagnetic fields.
Electromagnetic Biology and Medicine. Published online: 04 Feb 2021.
doi: 10.1080/15368378.2021.1881866
Abstract
This is a review of the research on the genetic effects of non-ionizing electromagnetic field (EMF), mainly on radiofrequency radiation (RFR) and static and extremely low frequency EMF (ELF-EMF). The majority of the studies are on genotoxicity (e.g., DNA damage, chromatin conformation changes, etc.) and gene expression. Genetic effects of EMF depend on various factors, including field parameters and characteristics (frequency, intensity, wave-shape), cell type, and exposure duration. The types of gene expression affected (e.g., genes involved in cell cycle arrest, apoptosis and stress responses, heat-shock proteins) are consistent with the findings that EMF causes genetic damages. Many studies reported effects in cells and animals after exposure to EMF at intensities similar to those in the public and occupational environments. The mechanisms by which effects are induced by EMF are basically unknown. Involvement of free radicals is a likely possibility. EMF also interacts synergistically with different entities on genetic functions. Interactions, particularly with chemotherapeutic compounds, raise the possibility of using EMF as an adjuvant for cancer treatment to increase the efficacy and decrease side effects of traditional chemotherapeutic drugs. Other data, such as adaptive effects and mitotic spindle aberrations after EMF exposure, further support the notion that EMF causes genetic effects in living organisms.
Excerpts
"Supplements 1 and 2 show that the majority of studies reported genetic effects of EMF (66% for RFR and 79% for static/ELF-EMF). Thus, it is safe to conclude that genotoxic effects of EMF have been reported. The most common effects found are: DNA strand breaks, micronucleus formation, and chromosomal structural changes. There are not many studies on mutation. Thus, it is not known whether these genotoxic effects transform into mutation and involved in carcinogenesis. Interestingly, available data do not suggest mutagenic effect after RFR exposure (Chang et al., 2005; Meltz et al., 1990; Ono et al., 2004; Takahashi et al., 2002); whereas most static/ELF-EMF studies (Chahal et al., 1993; Mairs et al., 2007; Miyakoshi, 1997; Miyakoshi et al., 1998, 1996; Potenza et al., 2004; Wilson et al., 2015) suggested some mutagenic effects...."
"There are similarly many studies that showed changes in gene expression after EMF exposure (Supplement 3). Changes in expression of many different genes have been reported. Studies in gene expression by static/ELF-EMF are far more diversified than those of RFR. The most interesting results are the expression of genes related to stress response both in vitro and in vivo in plans and animals. Another important finding is the expression of heat shock proteins, particularly HSP70, which is an important protein involved in protein misfolding and protecting cells from environmental stress...."
"Effects of EMF on cellular free radical processes have been reported in many experiments (cf. Lai, 2019; Yakymenko et al., 2016). It is conceivable that an increase in free radicals in cells could cause macromolecular damages including DNA. There are many reports on involvements of free radicals in genetic processes, including both reactive oxygen species and reactive nitrogen species...."
"There are many reports of genetic effects induced by low intensities of EMF. The studies are listed in Supplement 4. This is an important topic to consider since living organisms are being constantly exposed to low levels of EMF in the occupational and public environments. This is particularly true for ELF-EMF, since intensities of ELF-EMF in the environment are in microtesla (µT) levels, even exposure to fields from electrical appliances rarely exceed 10 microtesla (i.e., 0.01 mT). However, most laboratory cell and animal studies in ELF-EMF used fields in the millitesla (mT) level...."
"Another important observation of the studies is that EMF can interact with other entities and synergistically cause genetic effects.... Most of the compounds that have been shown to interact with EMF are mutagens. This is important because in real-life situations, a person is usually exposed simultaneously to EMF and many different environmental factors, including mutagens. "
"Two other important findings of recent studies are that the effects of EMF are waveform specific and cell-type specific (Supplement 5). These findings underscore the complicity of interaction of EMF with biological tissues and may partially explain why effects were observed in some studies and not others. It is essential to understand why and how certain wave-characteristics of an EMF are more effective than other characteristics in causing biological effects, and why certain types of cells are more susceptible to the effect of EMF? The fact that “there are different biological effects elicited by different EMF wave-characteristics” is a critical proof for the existence of non-thermal effects...."
"Regarding cell-type specificity, one can speculate that: 1. Cells that are metabolic active are more susceptible to EMF effects with an increase in generation of free radical in the mitochondria; 2. Cells that have higher anti-oxidative activities are less susceptible; 3. Transitional elements, e.g., iron, may play a role in the effect via the Fenton reaction (see Lai, 2019). Brain cells contain a relatively high concentration of free iron, particularly intercalated in the DNA molecules, and are more susceptible; 4. Cell cycle arrests are common in cells exposed to EMF. It may be a response to repair genetic damages caused by EMF. If damage could not be repaired, cell death occurs, particularly via apoptosis, which is a common outcome after EMF exposure. These effects are consistent with the gene expression studies, showing activation of genes involved in both cell death and repair. 5. If genetic damaged cells are allowed to survive, cancer may occur. However, if they die, the risk of cancer would actually be reduced. But, other detrimental health outcomes may occur, e.g., death of brain cells could lead to neurodegenerative diseases. Increased incidences of degenerative diseases..."
Discussion
"The main question is whether EMF exposure could cause genetic effects? It is pertinent here to quote a recent statement made by two prominent bioelectromagnetic researchers (Barnes and Greenebaum, 2020): “The evidence that weak radiofrequency (RF) and low-frequency fields can modify human health is still less strong, but the experiments supporting both conclusions are too numerous to be uniformly written off as a group due to poor technique, poor dosimetry, or lack of blinding in some cases, or other good laboratory practices.” All in all, in the studies reviewed in Supplements 1 and 2, approximately 70% of them showed effects. One could say that EMF exposure can lead to genetic changes. Some genetic damages could eventually lead to detrimental health effects. However, the mechanisms remain to be uncovered. But, knowing the mechanism is not necessary to accept that the data are valid. It is also a general criticism that most EMF studies cannot be replicated. I think it is a conceptual and factual mis-statement. Replication is also not a necessary and sufficient condition to believe that certain data are true. Scientific studies are hardly replicated. Rational funders do not generally fund replications. All scientists should know that it is very difficult to replicate exactly an experiment carried out by another lab. This is particularly true when the effects of EMF depend on many unknown factors. By the way, not many replication experiments have been carried out in EMF genetic-effect research to justify the statement that “data from EMF are not replicable”. In some cases, the experimenters deliberately changed the procedures of an experiment that they were supposed to be replicating and claimed that their experiment was a replication, for example, compare the experimental procedures of Lai and Singh (1995) and Malyapa et al. (1998).
To prove an effect, one should look for consistency in data. Genetic damage studies have shown similar effects with different set-up and in various biological systems. And, the gene expression results (Supplement 3) also support the studies on genetic damages. Expression of genes related to cell differentiation and growth, apoptosis, free radical activity, DNA repair, and heat-shock proteins have been reported. These changes could be consequences of EMF-induced genetic damages.... In conclusion, there are enough reasons to believe that genetic effects of EMF are real and possible.
During cell phone use, a relatively constant mass of tissue in the brain is exposed to the radiation at relatively high intensity (peak specific absorption rate (SAR) of 4–8 W/kg). Many papers have reported genetic effect/DNA damage at much lower SAR (or power density) (see Supplement 4). This questions the wisdom of the several exposure standard-setting organizations in using the obsolete data of 4 W/kg (whole-body averaged SAR) as the threshold for exposure-standard setting. Furthermore, since critical genetic mutations in one single cell are sufficient to lead to cancer and there are millions of cells in a gram of tissue, it is inconceivable that some standards have changed the SAR from averaged over 1 gm to 10 gm of tissue. (The limit of localized tissue exposure has been changed from 1.6 W/kg averaged over 1 gm of tissue to 2 W/kg over 10 gm of tissue. Since distribution of radiofrequency energy is non-homogenous inside tissues, this change allows a higher peak level of exposure.) What is actually needed is a better refinement of SAR calculation to identify ‘peak values’ of SAR inside the brain.
Any effect of EMF has to depend on the energy absorbed by a biological entity and on how the energy is delivered in space and time. Aside from influences that are not directly related to experimentation (Huss et al., 2007), many factors could influence the outcome of an experiment in bioelectromagnetics research. Frequency, intensity, exposure duration, and the number of exposure episodes can affect the response, and these factors can interact with each other to produce different effects. In addition, in order to understand the biological consequences of EMF exposure, one must know whether the effect is cumulative, whether compensatory responses result, and when homeostasis will break down. A drawback in the interpretation and understanding of experimental data from bioelectromagnetic research is that there is no general accepted mechanism on how EMF affects biological systems. Since the energy level is not sufficient to cause direct breakage of chemical bonds within molecules, the effects are probably indirect and secondary to other induced chemical changes in the cell. The mechanisms by which EMF causes genetic effects are unknown. This author suspects that biological effects of EMF exposure are caused by multiple inter-dependent biological mechanisms."
https://www.tandfonline.com/doi/abs/10.1080/15368378.2021.1881866
Abstract
This is a review of the research on the genetic effects of non-ionizing electromagnetic field (EMF), mainly on radiofrequency radiation (RFR) and static and extremely low frequency EMF (ELF-EMF). The majority of the studies are on genotoxicity (e.g., DNA damage, chromatin conformation changes, etc.) and gene expression. Genetic effects of EMF depend on various factors, including field parameters and characteristics (frequency, intensity, wave-shape), cell type, and exposure duration. The types of gene expression affected (e.g., genes involved in cell cycle arrest, apoptosis and stress responses, heat-shock proteins) are consistent with the findings that EMF causes genetic damages. Many studies reported effects in cells and animals after exposure to EMF at intensities similar to those in the public and occupational environments. The mechanisms by which effects are induced by EMF are basically unknown. Involvement of free radicals is a likely possibility. EMF also interacts synergistically with different entities on genetic functions. Interactions, particularly with chemotherapeutic compounds, raise the possibility of using EMF as an adjuvant for cancer treatment to increase the efficacy and decrease side effects of traditional chemotherapeutic drugs. Other data, such as adaptive effects and mitotic spindle aberrations after EMF exposure, further support the notion that EMF causes genetic effects in living organisms.
Excerpts
"Supplements 1 and 2 show that the majority of studies reported genetic effects of EMF (66% for RFR and 79% for static/ELF-EMF). Thus, it is safe to conclude that genotoxic effects of EMF have been reported. The most common effects found are: DNA strand breaks, micronucleus formation, and chromosomal structural changes. There are not many studies on mutation. Thus, it is not known whether these genotoxic effects transform into mutation and involved in carcinogenesis. Interestingly, available data do not suggest mutagenic effect after RFR exposure (Chang et al., 2005; Meltz et al., 1990; Ono et al., 2004; Takahashi et al., 2002); whereas most static/ELF-EMF studies (Chahal et al., 1993; Mairs et al., 2007; Miyakoshi, 1997; Miyakoshi et al., 1998, 1996; Potenza et al., 2004; Wilson et al., 2015) suggested some mutagenic effects...."
"There are similarly many studies that showed changes in gene expression after EMF exposure (Supplement 3). Changes in expression of many different genes have been reported. Studies in gene expression by static/ELF-EMF are far more diversified than those of RFR. The most interesting results are the expression of genes related to stress response both in vitro and in vivo in plans and animals. Another important finding is the expression of heat shock proteins, particularly HSP70, which is an important protein involved in protein misfolding and protecting cells from environmental stress...."
"Effects of EMF on cellular free radical processes have been reported in many experiments (cf. Lai, 2019; Yakymenko et al., 2016). It is conceivable that an increase in free radicals in cells could cause macromolecular damages including DNA. There are many reports on involvements of free radicals in genetic processes, including both reactive oxygen species and reactive nitrogen species...."
"There are many reports of genetic effects induced by low intensities of EMF. The studies are listed in Supplement 4. This is an important topic to consider since living organisms are being constantly exposed to low levels of EMF in the occupational and public environments. This is particularly true for ELF-EMF, since intensities of ELF-EMF in the environment are in microtesla (µT) levels, even exposure to fields from electrical appliances rarely exceed 10 microtesla (i.e., 0.01 mT). However, most laboratory cell and animal studies in ELF-EMF used fields in the millitesla (mT) level...."
"Another important observation of the studies is that EMF can interact with other entities and synergistically cause genetic effects.... Most of the compounds that have been shown to interact with EMF are mutagens. This is important because in real-life situations, a person is usually exposed simultaneously to EMF and many different environmental factors, including mutagens. "
"Two other important findings of recent studies are that the effects of EMF are waveform specific and cell-type specific (Supplement 5). These findings underscore the complicity of interaction of EMF with biological tissues and may partially explain why effects were observed in some studies and not others. It is essential to understand why and how certain wave-characteristics of an EMF are more effective than other characteristics in causing biological effects, and why certain types of cells are more susceptible to the effect of EMF? The fact that “there are different biological effects elicited by different EMF wave-characteristics” is a critical proof for the existence of non-thermal effects...."
"Regarding cell-type specificity, one can speculate that: 1. Cells that are metabolic active are more susceptible to EMF effects with an increase in generation of free radical in the mitochondria; 2. Cells that have higher anti-oxidative activities are less susceptible; 3. Transitional elements, e.g., iron, may play a role in the effect via the Fenton reaction (see Lai, 2019). Brain cells contain a relatively high concentration of free iron, particularly intercalated in the DNA molecules, and are more susceptible; 4. Cell cycle arrests are common in cells exposed to EMF. It may be a response to repair genetic damages caused by EMF. If damage could not be repaired, cell death occurs, particularly via apoptosis, which is a common outcome after EMF exposure. These effects are consistent with the gene expression studies, showing activation of genes involved in both cell death and repair. 5. If genetic damaged cells are allowed to survive, cancer may occur. However, if they die, the risk of cancer would actually be reduced. But, other detrimental health outcomes may occur, e.g., death of brain cells could lead to neurodegenerative diseases. Increased incidences of degenerative diseases..."
Discussion
"The main question is whether EMF exposure could cause genetic effects? It is pertinent here to quote a recent statement made by two prominent bioelectromagnetic researchers (Barnes and Greenebaum, 2020): “The evidence that weak radiofrequency (RF) and low-frequency fields can modify human health is still less strong, but the experiments supporting both conclusions are too numerous to be uniformly written off as a group due to poor technique, poor dosimetry, or lack of blinding in some cases, or other good laboratory practices.” All in all, in the studies reviewed in Supplements 1 and 2, approximately 70% of them showed effects. One could say that EMF exposure can lead to genetic changes. Some genetic damages could eventually lead to detrimental health effects. However, the mechanisms remain to be uncovered. But, knowing the mechanism is not necessary to accept that the data are valid. It is also a general criticism that most EMF studies cannot be replicated. I think it is a conceptual and factual mis-statement. Replication is also not a necessary and sufficient condition to believe that certain data are true. Scientific studies are hardly replicated. Rational funders do not generally fund replications. All scientists should know that it is very difficult to replicate exactly an experiment carried out by another lab. This is particularly true when the effects of EMF depend on many unknown factors. By the way, not many replication experiments have been carried out in EMF genetic-effect research to justify the statement that “data from EMF are not replicable”. In some cases, the experimenters deliberately changed the procedures of an experiment that they were supposed to be replicating and claimed that their experiment was a replication, for example, compare the experimental procedures of Lai and Singh (1995) and Malyapa et al. (1998).
To prove an effect, one should look for consistency in data. Genetic damage studies have shown similar effects with different set-up and in various biological systems. And, the gene expression results (Supplement 3) also support the studies on genetic damages. Expression of genes related to cell differentiation and growth, apoptosis, free radical activity, DNA repair, and heat-shock proteins have been reported. These changes could be consequences of EMF-induced genetic damages.... In conclusion, there are enough reasons to believe that genetic effects of EMF are real and possible.
During cell phone use, a relatively constant mass of tissue in the brain is exposed to the radiation at relatively high intensity (peak specific absorption rate (SAR) of 4–8 W/kg). Many papers have reported genetic effect/DNA damage at much lower SAR (or power density) (see Supplement 4). This questions the wisdom of the several exposure standard-setting organizations in using the obsolete data of 4 W/kg (whole-body averaged SAR) as the threshold for exposure-standard setting. Furthermore, since critical genetic mutations in one single cell are sufficient to lead to cancer and there are millions of cells in a gram of tissue, it is inconceivable that some standards have changed the SAR from averaged over 1 gm to 10 gm of tissue. (The limit of localized tissue exposure has been changed from 1.6 W/kg averaged over 1 gm of tissue to 2 W/kg over 10 gm of tissue. Since distribution of radiofrequency energy is non-homogenous inside tissues, this change allows a higher peak level of exposure.) What is actually needed is a better refinement of SAR calculation to identify ‘peak values’ of SAR inside the brain.
Any effect of EMF has to depend on the energy absorbed by a biological entity and on how the energy is delivered in space and time. Aside from influences that are not directly related to experimentation (Huss et al., 2007), many factors could influence the outcome of an experiment in bioelectromagnetics research. Frequency, intensity, exposure duration, and the number of exposure episodes can affect the response, and these factors can interact with each other to produce different effects. In addition, in order to understand the biological consequences of EMF exposure, one must know whether the effect is cumulative, whether compensatory responses result, and when homeostasis will break down. A drawback in the interpretation and understanding of experimental data from bioelectromagnetic research is that there is no general accepted mechanism on how EMF affects biological systems. Since the energy level is not sufficient to cause direct breakage of chemical bonds within molecules, the effects are probably indirect and secondary to other induced chemical changes in the cell. The mechanisms by which EMF causes genetic effects are unknown. This author suspects that biological effects of EMF exposure are caused by multiple inter-dependent biological mechanisms."
https://www.tandfonline.com/doi/abs/10.1080/15368378.2021.1881866
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