Radiofrequency radiation-induced gene expression
Lai H, Levitt BB. Radiofrequency radiation-induced gene expression. Rev Environ Health. 2025 Oct 29. doi: 10.1515/reveh-2025-0104.
Abstract
Genes are differentially expressed in cells in response to changes in the internal or external environment. The response is generally an adaptive mechanism to the environmental challenge to restore cell functions to homeostasis. There are numerous studies reporting changes in gene expression in cells exposed to radiofrequency radiation (RFR), the type of energy emitted by wireless communication devices. The major genes affected are those involved in: repair of damaged proteins, response to stress, oxidative changes, apoptosis, DNA damage detection and repair, and changes in neural functions. Gene expression data supports the notion that RFR is a stressor that causes oxidative changes and DNA and protein damage in cells under different exposure conditions, in many biological systems. Changes in all these significant gene expression effects are supported by results of other biological studies of RFR exposure in the literature. They should be considered in the setting of RFR-exposure guidelines.
Excerpts
"Gene expressions are under feedback control in response to external challenges with numerous variables. RFR has a complex interaction with living organisms depending on various parameters of the field. With these considerations in mind, response oscillation and non-linear dose-response could occur. But gene expression is not expected under all exposure conditions and biological systems studied. Thus, inevitably, in some studies, no significant effects would be expected. There are studies that reported no significant effect of RFR on gene expression related to protein damage and removal, DNA, oxidative processes, stress, and brain functions (Table 7)."
"Forty gene expression effects (marked as low intensity (LI) in Tables 1–6) were observed at a SAR less than 0.4 W/kg. This is relevant to the effects of exposure to RFR in the environment. 0.4 W/kg is the dose rate assumed to be safe by international radiofrequency radiation guidelines (e.g., the International Commission on Non-Ionizing Radiation Protection (ICNIRP) and the International Electronics and Electrical Engineers (IEEE)). This is important to understand regarding the validity of those organization’s high-intensity standards-setting models. (For readers who are interested in ‘low-intensity’ RFR effects, there are more than 200 studies that reported biological effects at SAR <0.4 W/kg [see the ‘RFR-low-intensity studies’ file in reference [1]]).
Lastly, one may wonder whether up-regulation of gene expression would lead to translation into functional proteins. Several RFR studies support increased translation (e.g., [33], [34], [35], [36]). It is an important complement to the gene-expression studies to look at translation levels of proteins as these are the functional units that promote/sustain both health and illness. Proteomic studies are an attractive next step in understanding the biological effects of RFR exposure. This was suggested more than a decade ago [37]. Changes in transcription and protein functions point to a need to investigate molecular signaling pathways after RFR exposure [38]. In addition, the data on gene-expression suggests two areas of mechanism research that are worth pursuing. The first area is the involvement of stress in RFR-induced biological effects. Involvements of ‘cellular stress responses’ and the hypothalamic-pituitary-adrenal axis and, particularly, effects on the limbic system should be further investigated [3]. The second area is the cellular oxidative processes. Particularly, the mechanism of induction of free radicals by RFR should be systematically studied. Present data indicates that low-frequency modulations in RFR may play a role [39]. It is, however, not known how much these low-frequency components contribute to the overall effect. Similar effects on gene expression have been reported after exposure to extremely-low frequency electromagnetic fields (see ‘static and ELF EMF genetic effects’ file in reference [1])."
Open access: https://www.degruyterbrill.com/document/doi/10.1515/reveh-2025-0104/html
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A scoping review and evidence map of radiofrequency field exposure and genotoxicity: assessing in vivo, in vitro, and epidemiological data
Weller
SG, McCredden JE, Leach V, Chu C, Lam AK-Y (2025) A scoping review and
evidence map of radiofrequency field exposure and genotoxicity:
assessing in vivo, in vitro, and epidemiological data. Front. Public
Health 13:1613353. doi: 10.3389/fpubh.2025.1613353.
Abstract
Background
Studies investigating genotoxic effects of radiofrequency
electromagnetic field (RF-EMF) exposure (3 kHz−300 GHz) have used a wide
variety of parameters, and results have been inconsistent. A systematic
mapping of existing research is necessary to identify emerging patterns
and to inform future research and policy.
Methods
Evidence mapping was conducted using guidance from the Preferred
Reporting Items for Systematic reviews and Meta-Analyses for Scoping
Reviews (PRISMA-ScR). A comprehensive search strategy was applied across
multiple research databases, using specific inclusion and exclusion
criteria within each knowledge domain. Quantitative aggregation using
tables, graphs and heat maps was used to synthesize data according to
study type, organism type, exposure level and duration, biological
markers (genotoxicity, cellular stress, apoptosis), RF-EMF signal
characteristics, as well as funding source to further contextualize the
evidence landscape. Quality criteria were applied as part of a focused
analysis to explore potential biases and their effects on outcomes.
Results
Over 500 pertinent studies were identified, categorized as in vitro
(53%), in vivo (37%), and epidemiological (10%), and grouped according
to type of DNA damage, organism, intensity, duration, signal
characteristics, biological markers and funding source. In vitro studies
predominantly showed proportionally fewer significant effects, while in
vivo and epidemiological studies showed more. DNA base damage studies
showed the highest proportion of effects, as did studies using GSM
talk-mode, pulsed signals and real-world devices. A complex relationship
was identified between exposure intensity and duration, with duration
emerging as a critical determinant of outcomes. A complex U-shaped
dose-response relationship was evident, suggesting adaptive cellular
responses, with increased free radical production as a plausible
mechanism. Higher-quality studies showed fewer significant effects;
however, the funding source had a stronger influence on outcomes than
study quality. Over half (58%) of studies observing DNA damage used
exposures below the International Commission of Non-Ionizing Radiation
Protection (ICNIRP) limits.
Conclusion
The collective evidence reveals that RF-EMF exposures may be genotoxic
and could pose a cancer risk. Exposure duration and real-world signals
are the most important factors influencing genotoxicity, warranting
further focused research. To address potential genotoxic risks, these
findings support the adoption of precautionary measures alongside
existing thermal-based exposure guidelines.
Excerpts
Implications for policy and practice
The evidence from the evidence map indicates that medium to long-term RF-EMF exposures, particularly at low intensities, can induce genetic damage through non-thermal mechanisms such as increased free radical production and oxidative stress. Genetic damage can have far-reaching, long-term, and potentially irreversible consequences for individual organisms and broader ecological and planetary health (112, 113).
Both In vivo and epidemiological RF-EMF studies provide credible evidence of genotoxicity, suggesting potential risks such as increased cancer susceptibility and reproductive harm. Studies on brain cells frequently reported positive findings for DNA damage, suggesting that brain cells may be particularly sensitive to RF-EMF, indicating a risk for neurological diseases and brain tumors, as observed in animal models (114–116).
Current RF-EMF exposure guidelines established by ICNIRP (15), prioritize the prevention of thermal effects by incorporating substantial safety margins (e.g., a 50-fold reduction from effect thresholds, setting a local SAR limit of 2 W/kg for the head and torso for the general public, averaged over 10 grams of tissue). However, the evidence mapping process found statistically significant DNA damage at extremely low intensities, with the lowest recorded effects occurring at a SAR of 0.000000319 W/kg in an epidemiological study (117) and at 0.000003 W/kg in several in vivo experiments (118, 119). These levels are substantially (>600,000 times) below the ICNIRP public exposure limits (15). This pattern suggests non-thermal genotoxic effects, because temperature changes at these intensities would be negligible and not measurable.
ICNIRP (2020) guidelines (15) set RF-EMF exposure limits to protect against thermal effects from acute exposures, with averaging times of 6 min for local exposure (head and torso) and 30 min for whole-body exposure. However, the above analysis revealed that medium (1 day−3 months) and long-term RF-EMF exposures (>3 months or 1,000 h) were most strongly linked to genotoxic effects, even at very low exposure intensities. ICNIRP (2020) guidelines (15) do not set specific limits for chronic, low-level RF-EMF exposures, particularly for non-thermal effects like genotoxicity, citing “no substantiated evidence of health-relevant effects” [(15), p. 522].
The mapping process also revealed that RF exposures are associated with genetic damage in a wide range of organisms, with an observed sensitivity of non-mammalian organisms, such as plants, insects, and possibly amphibians. Current guidelines neglect potential effects on wildlife or ecosystems (78, 96). Notably, a recent WHO-commissioned systematic review of animal studies suggested carcinogenic effects from RF-EMF exposures (116). Other studies suggest biological effects on non-human species (120, 121). Together, these results suggest that the environmental implications of RF-EMF exposure merit greater scrutiny (122), even though the current evidence remains limited and debated (96).
While these findings do not yet establish causation or a clear No Observed Adverse Effect Level (NOAEL), they indicate risks that ICNIRP's current framework discounts by prioritizing only effects with confirmed harm [(15), p. 487]. ICNIRP's review process and position is best described as a hazard-based assessment focused only on confirmed effects. This approach is overly restrictive, as it delays updating guidelines until absolute certainty is achieved (123), which may not align with the precautionary needs of public health or environmental protection.
Currently, there is a widespread (6) and often non-consensual nature to RF-EMF exposure (92) from mobile phones, base stations, and other wireless technologies. While acknowledging the permanence of this technology in modern society, policy adjustments are required that prioritize health and environmental protection over economic interests. This can be achieved by adopting a precautionary approach to RF-EMF (123) and addressing potential risks from non-thermal RF-EMF effects, despite scientific uncertainty. Strategies such as justification (assessing net benefits of RF-EMF applications), optimization (balancing protection with societal needs), and As low as Reasonably Achievable or As Low as Technically Achievable - ALARA/ALATA (avoiding deterministic effects and minimizing stochastic effects) per International Commission on Radiological Protection (ICRP) recommendations - ICRP103 (124) could be considered. Further development and deployment of wireless technologies should incorporate improved safety measures in their design (125), such as creating devices that emit lower levels of RF-EMF or using materials and antenna designs to direct emissions away from the body.
Additionally, public information regarding potential health risks and personal protective measures could be disseminated through public health campaigns, making use of existing advice such as the EUROPAEM EMF Guideline 2016 (126); e.g. minimizing the use of wireless devices, prioritizing wired connections, maintaining distance between RF-EMF sources and the body, use of air-tube headsets or handsfree calls, turning off wireless when not in use, and mitigation of oxidative stress by incorporating antioxidants into the diet.
While individual actions are valuable, they are not a substitute for robust regulatory standards and industry accountability. Ensuring the safety of wireless technologies requires a collective effort from manufacturers, policymakers, and consumers to develop comprehensive RF safety guidelines. Future regulatory guidelines could encompass workplace protection measures, including substitution, engineering, and administrative controls (127), integration of building biology standards (128), mandatory detailed product labeling to inform users of potential risks, and standardized safety hygiene practices.
Recommended actions
To address these concerns and bridge existing gaps, the following actions are recommended:
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Standardization of Research Protocols: Harmonizing methodologies across studies, particularly comet assay protocols, is critical for reducing heterogeneity and enabling robust meta-analyses.
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Focus on Long-Term and Low-Intensity Exposures: Future research should prioritize investigating the cumulative effects of prolonged and low-intensity RF-EMF exposures, which are most relevant to real-world scenarios and devices.
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Inclusion of Emerging Frequencies: Given the rapid deployment of 5G and other novel technologies, research focused on higher frequencies and new modulation schemes is urgently needed.
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Targeted Environmental and Health Studies: Targeted research in both human health and ecological systems needs to be conducted independently of vested interest influences, ensuring methodological rigor in each domain.
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Independent Funding and Research Oversight: To mitigate biases associated with industry funding, greater support for independent research is essential. Transparent disclosure of ALL funding sources and researcher affiliations should be mandatory.
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Re-evaluation of RF Standards: Regulatory bodies must update exposure guidelines to reflect non-thermal mechanisms and the potential health effects from long-term chronic exposure settings by incorporating findings from independent, high-quality studies.
Conclusions
The evidence map presented here reveals statistically significant DNA damage in humans and animals resulting from man-made RF-EMF exposures, particularly DNA base damage and DNA strand breaks. The evidence also suggests plausible mechanistic pathways for DNA damage, most notably through increased free radical production and oxidative stress. Sensitivity to damage varied by cell type, with reproductive cells (testicular, sperm and ovarian) along with brain cells appearing particularly vulnerable. A complex U-shaped dose-response relationship was observed for both exposure duration and intensity, with more DNA damage occurring in specific frequency and intensity combination windows. DNA damage was more likely to be found using in vivo studies, very weak or very strong signal intensities, very short or very long exposure durations, 900, 1,800 and 2,450 MHz frequencies, GSM-talk mode and pulsed modulations, particularly when using real-world devices. On the other hand, research funded by vested interests has tended to use different experimental design parameters, with a high proportion of studies using in vitro, short-term exposures, medium-high intensity signals and using signal generators. Funding source is also a stronger determinant of experimental outcomes than study quality.
Overall, there is a strong evidence base showing DNA damage and potential biological mechanisms operating at intensity levels much lower than the ICNIRP recommended exposure limits. Public policy could benefit from the implementation of precautionary measures such as ALARA or ALATA, along with public information campaigns to better safeguard human and environmental health and wellbeing.
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Genetic effects of non-ionizing electromagnetic fields
Lai H. Genetic effects of non-ionizing electromagnetic fields. Electromagn Biol Med. 2021 Apr 3;40(2):264-273. 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...."
"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..."
"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."
Report Overview
Key Findings
Conclusion
Neurological / Vestibular Endpoints
Reproductive / Fertility Endpoints
Cross‑cutting Methodological Priorities
Actionable Checklist