The effect of exposure to radiofrequency LTE signal and coexposure to mitomycin-C in Chinese hamster lung fibroblast V79 cells.

This study aims to investigate the cellular effects of radiofrequency exposure, 1950 MHz, long-term evolution (LTE) signal, administered alone and in combination with mitomycin-C (MMC), a well-known cytotoxic agent. Chinese hamster lung fibroblast (V79) cells were exposed/sham exposed in a waveguide-based system under strictly controlled conditions of both electromagnetic and environmental parameters, at specific absorption rate (SAR) of 0.3 and 1.25 W/kg. Chromosomal damage (micronuclei formation), oxidative stress (reactive oxygen species [ROS] formation), and cell cycle progression were analyzed after exposure and coexposure. No differences between exposed samples and sham-controls were detected following radiofrequency exposure alone, for all the experimental conditions tested and biological endpoints investigated. When radiofrequency exposure was followed by MMC treatment, 3 h pre-exposure did not modify MMC-induced micronuclei. Pre-exposure of 20 h at 0.3 W/kg did not modify the number of micronuclei induced by MMC, while 1.25 W/kg resulted in a significant reduction of MMC-induced damage. Absence of effects was also detected when CW was used, at both SAR levels. MMC-induced ROS formation resulted significantly decreased at both SAR levels investigated, while cell proliferation and cell cycle progression were not affected by coexposures. The results here reported provide no evidence of direct effects of 1950 MHz, LTE signal. Moreover, they further support our previous findings on the capability of radiofrequency pre-exposure to induce protection from a subsequent toxic treatment, and the key role of the modulated signals and the experimental conditions adopted in eliciting the effect.

Radiofrequency Electromagnetic Field Exposure and Apoptosis: A Scoping Review of In Vitro Studies on Mammalian Cells.

In the last decades, experimental studies have been carried out to investigate the effects of radiofrequency (RF, 100 kHz-300 GHz) electromagnetic fields (EMF) exposure on the apoptotic process. As evidence-based critical evaluation of RF and apoptosis in vitro is lacking, we performed a scoping literature review with the aim of systematically mapping the research performed in this area and identifying gaps in knowledge. Eligible for inclusion were in vitro studies assessing apoptosis in mammalian cells exposed to RF-EMF, which met basic quality criteria (sham control, at least three independent experiments, appropriate dosimetry analysis and temperature monitoring). We conducted a systematic literature review and charted data in order to overview the main characteristics of included studies. From the 4362 papers retrieved with our search strategy, 121 were pertinent but, among them, only 42 met basic quality criteria. We pooled data with respect to exposure (frequency, exposure level and duration) and biological parameters (cell type, endpoint), and highlighted some qualitative trends with respect to the detection of significant effect of RF-EMF on the apoptotic process. We provided a qualitative picture of the evidence accumulated so far, and highlighted that the quality of experimental methodology still needs to be highly improved.

Inhibition of Autophagy Negates Radiofrequency-Induced Adaptive Response in SH-SY5Y Neuroblastoma Cells.

In the last years, radiofrequency (RF) has demonstrated that it can reduce DNA damage induced by a subsequent treatment with chemical or physical agents in different cell types, resembling the adaptive response, a phenomenon well documented in radiobiology. Such an effect has also been reported by other authors both in vitro and in vivo, and plausible hypotheses have been formulated, spanning from the perturbation of the cell redox status, to DNA repair mechanisms, and stress response machinery, as possible cellular mechanisms activated by RF pre-exposure. These mechanisms may underpin the observed phenomenon, and require deeper investigations. The present study aimed to determine whether autophagy contributes to RF-induced adaptive response. To this purpose, SH-SY5Y human neuroblastoma cells were exposed for 20 h to 1950 MHz, UMTS signal, and then treated with menadione. The results obtained indicated a reduction in menadione-induced DNA damage, assessed by applying the comet assay. Such a reduction was negated when autophagy was inhibited by bafilomycin A1 and E64d. Moreover, CRISPR SH-SY5Y cell lines defective for ATG7 or ATG5 genes did not show an adaptive response. These findings suggest the involvement of autophagy in the RF-induced adaptive response in human neuroblastoma cells; although, further investigation is required to extend such observation at the molecular level.

Evidence of bystander effect induced by radiofrequency radiation in a human neuroblastoma cell line.

In previous studies we demonstrated that radiofrequency (RF) electromagnetic fields (EMF) is able to reduce DNA damage induced by a subsequent treatment with genotoxic agents, resembling the adaptive response, a phenomenon well known in radiobiology. In this study we report on the capability of the culture medium from SH-SY5Y neuroblastoma cells exposed to 1950 MHz to elicit, in recipient non-exposed cells, a reduction of menadione-induced DNA damage (P < 0.05; comet assay), indicating the capability of non-ionizing radiation to elicit a bystander effect. A comparable reduction was also detected in cultures directly exposed to the same EMF conditions (P < 0.05), confirming the adaptive response. In the same exposure conditions, we also evidenced an increase of heat shock protein 70 (hsp70) in culture medium of cells exposed to RF with respect to sham exposed ones (P < 0.05; western blot analysis), while no differences were detected in the intracellular content of hsp70. On the whole, our results evidence a protective effect of RF against menadione-induced DNA damage in directly and non-directly exposed cells, and suggest hsp70 pathway to be investigated as one of the potential candidate underpinning the interaction between RF exposure and biological systems.

Adverse and beneficial effects in Chinese hamster lung fibroblast cells following radiofrequency exposure.

In this study, the effect of radiofrequency (RF) exposure to 1950 MHz, Universal Mobile Telecommunication System signal, was investigated in Chinese hamster lung fibroblast cell line (V79). Genotoxic and cytotoxic effects of 20-h exposure at specific absorption rate (SAR) values from 0.15 W/kg to 1.25 W/kg were measured by means of cytokinesis-block micronucleus (MN) assay. Exposure was carried out blinded under strictly controlled conditions of dosimetry and temperature. The effect of RF exposure alone at four SAR values was tested, that is, 0.15, 0.3, 0.6, and 1.25 W/kg. A statistically significant increase in MN frequency was found in cultures exposed to 0.15 and 0.3 W/kg (P < 0.05) compared to sham-exposed ones, in the absence of cytotoxicity. SAR values of 0.6 and 1.25 W/kg did not exert any effect. Moreover, to evaluate the ability of RF to exert protective effects with respect to a chemical mutagen, cell cultures were also pre-exposed for 20 h at 0.3 or 1.25 W/kg, and then treated with 500 ng/ml of mitomycin-C (MMC). A significant reduction in the frequency of MN was detected in cultures pre-exposed to 1.25 W/kg compared to cultures treated with MMC alone (P < 0.05), indicating induction of adaptive response. Such a decrease was not induced by pre-exposure at 0.3 W/kg SAR. Taken together, our results indicated that V79 is a sensitive cell model to evidence either adverse or beneficial effects of RF exposure, depending on experimental conditions applied. Bioelectromagnetics. 38:245-254, 2017. © 2017 Wiley Periodicals, Inc.

Exposure classification of MRI workers in epidemiological studies.

We estimate that there are about 100,000 workers from different disciplines, such as radiographers, nurses, anesthetists, technicians, engineers, etc., who can be exposed to substantial electromagnetic fields (compared to normal background levels) around magnetic resonance imaging (MRI) scanners. There is a need for well-designed epidemiological studies of MRI workers but since the exposure from MRI equipment is a very complex mixture of static magnetic fields, switched gradient magnetic fields, and radiofrequency electromagnetic fields (RF EMF), it is necessary to discuss how to assess the exposure in epidemiological studies. As an alternative to the use of job title as a proxy of exposure, we propose an exposure categorization for the different professions working with MRI equipment. Specifically, we propose defining exposure in three categories, depending on whether people are exposed to only the static field, to the static plus switched gradient fields or to the static plus switched gradient plus RF fields, as a basis for exposure assessment in epidemiological studies.

NextGEM: Next-Generation Integrated Sensing and Analytical System for Monitoring and Assessing Radiofrequency Electromagnetic Field Exposure and Health.

The evolution of emerging technologies that use Radio Frequency Electromagnetic Field (RF-EMF) has increased the interest of the scientific community and society regarding the possible adverse effects on human health and the environment. This article provides NextGEM's vision to assure safety for EU citizens when employing existing and future EMF-based telecommunication technologies. This is accomplished by generating relevant knowledge that ascertains appropriate prevention and control/actuation actions regarding RF-EMF exposure in residential, public, and occupational settings. Fulfilling this vision, NextGEM commits to the need for a healthy living and working environment under safe RF-EMF exposure conditions that can be trusted by people and be in line with the regulations and laws developed by public authorities. NextGEM provides a framework for generating health-relevant scientific knowledge and data on new scenarios of exposure to RF-EMF in multiple frequency bands and developing and validating tools for evidence-based risk assessment. Finally, NextGEM's Innovation and Knowledge Hub (NIKH) will offer a standardized way for European regulatory authorities and the scientific community to store and assess project outcomes and provide access to findable, accessible, interoperable, and reusable (FAIR) data.

Induction of an adaptive response in human blood lymphocytes exposed to radiofrequency fields: influence of the universal mobile telecommunication system (UMTS) signal and the specific absorption rate.

The induction of an adaptive response (AR) was examined in human peripheral blood lymphocytes exposed to non-ionizing radiofrequency fields (RF). Cells from nine healthy human volunteers were stimulated for 24h with phytohaemagglutinin and then exposed for 20h to an adaptive dose (AD) of a 1950MHz RF UMTS (universal mobile telecommunication system) signal used for mobile communications, at different specific absorption rates (SAR) of 1.25, 0.6, 0.3, and 0.15W/kg. This was followed by treatment of the cells at 48h with a challenge dose (CD) of 100ng/ml mitomycin C (MMC). Lymphocytes were collected at the end of the 72h total culture period. The cytokinesis-block method was used to record the frequency of micronuclei (MN) as genotoxicity end-point. When lymphocytes from six donors were pre-exposed to RF at 0.3W/kg SAR and then treated with MMC, these cells showed a significant reduction in the frequency of MN, compared with the cells treated with MMC alone; this result is indicative of induction of AR. The results from our earlier study indicated that lymphocytes that were stimulated for 24h, exposed for 20h to a 900MHz RF GSM (global system for mobile communication) signal at 1.25W/kg SAR and then treated with 100ng/ml MMC, also exhibited AR. These overall data suggest that the induction of AR depends on RF frequency, type of the signal and SAR. Further characterization of RF-induced AR is in progress.

Occupational exposure to electromagnetic fields in magnetic resonance environment: an update on regulation, exposure assessment techniques, health risk evaluation, and surveillance.

Magnetic resonance imaging (MRI) is one of the most-used diagnostic imaging methods worldwide. There are ∼50,000 MRI scanners worldwide each of which involves a minimum of five workers from different disciplines who spend their working days around MRI scanners. This review analyzes the state of the art of literature about the several aspects of the occupational exposure to electromagnetic fields (EMF) in MRI: regulations, literature studies on biological effects, and health surveillance are addressed here in detail, along with a summary of the main approaches for exposure assessment. The original research papers published from 2013 to 2021 in international peer-reviewed journals, in the English language, are analyzed, together with documents published by legislative bodies. The key points for each topic are identified and described together with useful tips for precise safeguarding of MRI operators, in terms of exposure assessment, studies on biological effects, and health surveillance.

Genotoxicity of radiofrequency electromagnetic fields: Protocol for a systematic review of in vitro studies.

BACKGROUND: Exposure to radiofrequency electromagnetic fields (RF-EMF, 100 kHz - 300 GHz) emitted by wireless communication technologies is pervasive and ubiquitous. Concern has been raised about possible adverse effects to human health. In 2011 the International Agency for Research on Cancer has classified RF-EMF as possibly carcinogenic to humans, highlighting that the evidence is weak and far from conclusive. Updated systematic reviews of the scientific literature on this topic are lacking, especially for mechanistic studies. OBJECTIVES: To develop a protocol for a systematic review of experimental studies investigating genotoxic effects induced by RF-EMF in in vitro cellular models. Genotoxicity is one of the key-biological indicators of carcinogenicity, and the most common characteristics of established carcinogens. The predefined procedures for conducting the systematic review are outlined below. METHODS: We will follow the guidelines developed by the National Toxicology Program-Office of Health Assessment and Translation (NTP-OHAT), adapted to the evaluation of in vitro studies. ELIGIBILITY CRITERIA: We will include experimental in vitro studies addressing the relationship between controlled exposures to RF-EMF and genotoxicity in mammalian cells only. Eligibility for inclusion will be further restricted to peer reviewed articles reporting findings from primary studies. INFORMATION SOURCES: We will search the scientific literature databases NCBI PubMed, Web of Science, and EMF-Portal. No filter on publication date will be applied. Only studies published in English will be considered. The reference lists of the included papers and available reviews will be screened for unidentified relevant papers. References will be managed through Endnote X9 software. DATA EXTRACTION AND SYNTHESIS OF RESULTS: Data from included papers will be extracted according to predefined forms. Heterogeneity within the available evidence will determine the type of evidence synthesis that is appropriate. Findings will be summarized in tables, graphical displays and in a narrative synthesis of the available evidences. A meta-analysis will be carried out if subgroups of studies homogeneous in terms of exposure characteristics, endpoint, and cell types will be identified. RISK OF BIAS: The internal validity of included studies will be assessed using the NTP-OHAT Risk of Bias Rating Tool for animal studies, adapted to in vitro studies. This stage of the process will be managed through the Health Assessment Workspace Collaborative (HAWC). EVIDENCE APPRAISAL: To rate confidence in the body of evidence, we will use the OHAT GRADE-based approach for animal studies. FRAMEWORK AND FUNDING: This protocol concerns one of the evidence streams considered in a larger systematic review of the scientific literature on the potential carcinogenicity of RF-EMF, performed by scientists from several Italian public research agencies. The project is supported by the Italian Workers' Compensation Authority (INAIL) in the framework of the CRA with the Istituto Superiore di Sanità "BRiC 2018/06 - Scientific evidence on the carcinogenicity of radiofrequency electromagnetic fields".

Modified Blumlein pulse-forming networks for bioelectrical applications.

Intense nanosecond pulsed electric fields (nsPEFs) have been shown to induce, on intracellular structures, interesting effects dependent on electrical exposure conditions (pulse length and amplitude, repetition frequency and number of pulses), which are known in the literature as "bioelectrical effects" (Schoenbach et al., IEEE Trans Plasma Sci 30:293-300, 2002). In particular, pulses with a shorter width than the plasma membrane charging time constant (about 100 ns for mammalian cells) can penetrate the cell and trigger effects such as permeabilization of intracellular membranes, release of Ca(2+) and apoptosis induction. Moreover, the observed effects have led to exploration of medical applications, like the treatment of melanoma tumors (Nuccitelli et al., Biochem Biophys Res Commun 343:351-360, 2006). Pulsed electric fields allowing such effects usually range from several tens to a few hundred nanoseconds in duration and from a few to several tens of megavolts per meter in amplitude (Schoenbach et al., IEEE Trans Diel Elec Insul 14:1088-1109, 2007); however, the biological effects of subnanosecond pulses have been also investigated (Schoenbach et al., IEEE Trans Plasma Sci 36:414-422, 2008). The use of such a large variety of pulse parameters suggests that highly flexible pulse-generating systems, able to deliver wide ranges of pulse durations and amplitudes, are strongly required in order to explore effects and applications related to different exposure conditions. The Blumlein pulse-forming network is an often-employed circuit topology for the generation of high-voltage electric pulses with fixed pulse duration. An innovative modification to the Blumlein circuit has been recently devised which allows generation of pulses with variable amplitude, duration and polarity. Two different modified Blumlein pulse-generating systems are presented in this article, the first based on a coaxial cable configuration, matching microscopic slides as a pulse-delivery system, and the other based on microstrip transmission lines and designed to match cuvettes for the exposure of cell suspensions.

Induction of adaptive response in human blood lymphocytes exposed to radiofrequency radiation.

The incidence of micronuclei was evaluated to assess the induction of an adaptive response to non-ionizing radiofrequency (RF) radiation in peripheral blood lymphocytes collected from five different human volunteers. After stimulation with phytohemagglutinin for 24 h, the cells were exposed to an adaptive dose of 900 MHz RF radiation used for mobile communications (at a peak specific absorption rate of 10 W/kg) for 20 h and then challenged with a single genotoxic dose of mitomycin C (100 ng/ml) at 48 h. Lymphocytes were collected at 72 h to examine the frequency of micronuclei in cytokinesis-blocked binucleated cells. Cells collected from four donors exhibited the induction of adaptive response (i.e., responders). Lymphocytes that were pre-exposed to 900 MHz RF radiation had a significantly decreased incidence of micronuclei induced by the challenge dose of mitomycin C compared to those that were not pre-exposed to 900 MHz RF radiation. These preliminary results suggested that the adaptive response can be induced in cells exposed to non-ionizing radiation. A similar phenomenon has been reported in cells as well as in animals exposed to ionizing radiation in several earlier studies. However, induction of adaptive response was not observed in the remaining donor (i.e., non-responder). The incidence of micronuclei induced by the challenge dose of mitomycin C was not significantly different between the cells that were pre-exposed and unexposed to 900 MHz RF radiation. Thus the overall data indicated the existence of heterogeneity in the induction of an adaptive response between individuals exposed to RF radiation and showed that the less time-consuming micronucleus assay can be used to determine whether an individual is a responder or non-responder.

Special Issue: "Electric, Magnetic, and Electromagnetic Fields in Biology and Medicine: From Mechanisms to Biomedical Applications".

The last decades have seen a huge increase in applications and devices using and emitting non-ionizing radiation, otherwise referred to as "electromagnetic fields" (EMF) [...].

Treatment with 3-Aminobenzamide Negates the Radiofrequency-Induced Adaptive Response in Two Cell Models.

In previous investigations, we demonstrated that pre-exposure of different cell cultures to radiofrequency fields can reduce the damage induced by genotoxic agents, an effect resembling the so-called adaptive response. In this study, we pre-exposed human peripheral blood lymphocytes and Chinese hamster lung fibroblast cell line to 1950 MHz, UMTS (Universal Mobile Telecommunication System) signal, for 20 h, and then treated cultures with Mitomycin-C. After confirming the induction of an adaptive response in terms of the reduction of micronuclei formation, we observed that such a response was negated by treatments with 3-aminobenzamide. Since 3-aminobenzamide is an inhibitor of poly (ADP-ribose) polymerase enzyme, which is involved in DNA repair, these results support the possible involvement of DNA repair mechanisms in radiofrequency-induced adaptive response.

Cytotoxicity Investigation on Cultured Human Blood Cells Treated with Single-Wall Carbon Nanotubes.

The single-wall carbon nanotubes (SWCNTs) are one of the new materials ofemerging technologies. They are becoming increasingly studied for the possibleapplications in electronics, optics and biology. In particular, very promising fields ofapplication are the development of optical biosensors and the intracellular drug delivery.Nevertheless, there is a paucity of information on their toxicological properties and onpotential human health risk. In the present study the SWCNTs were investigated for thepossible induction of toxicity in human blood cells. Cell growth, viability, apoptosis andmetabolic activity were evaluated in proliferating human peripheral blood lymphocytes. Inun-stimulated human leukocytes primary DNA damage was also evaluated. SWCNTsconcentrations ranging from 1 to 50 µg/ml were tested, and treatment duration varied from6 to 72 h, in accordance with the biological target investigated. A statistically significantdecrease in cell growth was found in cells treated with the highest concentrations (25 and50 µg/ml). Such decrease was not associated to cell death or apoptosis, but it wasdemonstrated to be related to a decrease in metabolic activity, as assessed by resazurinassay. Moreover, treatments of 6 h with SWCNTs concentrations of 1, 5 and 10 µg/mlfailed to induce primary DNA damage on the entire human leukocytes population.

Protective effect of 1950 MHz electromagnetic field in human neuroblastoma cells challenged with menadione.

This study aims to assess whether a 1950 MHz radiofrequency (RF) electromagnetic field could protect human neuroblastoma SH-SY5Y cells against a subsequent treatment with menadione, a chemical agent inducing DNA damage via reactive oxygen species formation. Cells were pre-exposed for 20 h to specific absorption rate of either 0.3 or 1.25 W/kg, and 3 h after the end of the exposure, they were treated with 10 µM menadione (MD) for 1 h. No differences were observed between sham- and RF-exposed samples. A statistically significant reduction in menadione-induced DNA damage was detected in cells pre-exposed to either 0.3 or 1.25 W/kg (P < 0.05). Moreover, our analyses of gene expression revealed that the pre-exposure to RF almost inhibited the dramatic loss of glutathione peroxidase-based antioxidant scavenging efficiency that was induced by MD, and in parallel strongly enhanced the gene expression of catalase-based antioxidant protection. In addition, RF abolished the MD-dependent down-regulation of oxoguanine DNA glycosylase, which is a critical DNA repairing enzyme. Overall, our findings suggested that RF pre-exposure reduced menadione-dependent DNA oxidative damage, most probably by enhancing antioxidant scavenging efficiency and restoring DNA repair capability. Our results provided some insights into the molecular mechanisms underlying the RF-induced adaptive response in human neuroblastoma cells challenged with menadione.

ESOPE-Equivalent Pulsing Protocols for Calcium Electroporation: An In Vitro Optimization Study on 2 Cancer Cell Models.

Reversible electroporation is used to increase the uptake of chemotherapeutic drugs in local tumor treatment (electrochemotherapy) by applying the pulsing protocol (8 rectangular pulses, 1000 V/cm, 100 µs) standardized in the framework of the European Standard Operating Procedure on Electrochemotherapy multicenter trial. Currently, new electrochemotherapy strategies are under development to extend its applicability to tumors with different histology. Electrical parameters and drug type are critical factors. A possible approach is to test pulse parameters different from European Standard Operating Procedure on Electrochemotherapy but with comparable electroporation yield (European Standard Operating Procedure on Electrochemotherapy-equivalent protocols). Moreover, the use of non-toxic drugs combined with electroporation represents the new frontier for electrochemotherapy applications; calcium electroporation has been recently proposed as a simple tool for anticancer therapy. In vitro investigations facilitate the optimization of electrical parameters and drugs for in vivo and clinical testing. In this optimization study, new pulsing protocols have been tested by increasing the pulse number and reducing the electric field with respect to the standard. European Standard Operating Procedure on Electrochemotherapy-equivalent protocols have been identified in HL-60 and A431 cancer cell models, and a higher sensitivity in terms of electroporation yield has been recorded in HL-60 cells. Moreover, cell killing efficacy of European Standard Operating Procedure on Electrochemotherapy-equivalent protocols has been demonstrated in the presence of increasing calcium concentrations on both cell lines. Equivalent European Standard Operating Procedure on Electrochemotherapy protocols can be used to optimize the therapeutic effects in the clinic, where different regions of the same cancer tissue, with different electrical properties, might result in a differential electroporation yield of the standard protocol over the same tissue, or, eventually, in an override of the operational limits of the instrument. Moreover, using calcium can help overcome the drawbacks of standard drugs (side effects, high costs, difficult handling, preparation, and storage procedures). These results support the possibility of new treatment options in both standard electrochemotherapy and calcium electroporation, with clear advantages in the clinic.

Formation of reactive oxygen species in L929 cells after exposure to 900 MHz RF radiation with and without co-exposure to 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone.

The aim of this study was to investigate the induction of reactive oxygen species in murine L929 fibrosarcoma cells exposed to radiofrequency (RF) radiation at 900 MHz, with or without co-exposure to 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX), a potent environmental carcinogen produced during chlorination of drinking water. Both continuous-wave and GSM mobile phone signals were applied for 10 or 30 min at specific absorption rates of 0.3 and 1 W/kg. Simultaneous sham exposures were performed for each exposure condition. MX treatment was performed at a subtoxic level of 500 microM, and the RF-field exposure was carried out during the first 10 or 30 min of the chemical treatment. The formation of reactive oxygen species was followed soon after the exposure and at different harvesting times until 1 h after RF-field treatment. The studied provided no indication that 900 MHz RF-field exposure, either alone or in combination with MX, induced formation of reactive oxygen species under any of the experimental conditions investigated. In contrast, exposure to MX resulted in a statistically significant increase in the formation of reactive oxygen species for all the treatment durations investigated, confirming that MX is an inductor of oxidative stress in L929 cells.

Cellular Response to ELF-MF and Heat: Evidence for a Common Involvement of Heat Shock Proteins?

It has been shown that magnetic fields in the extremely low frequency range (ELF-MF) can act as a stressor in various in vivo or in vitro systems, at flux density levels below those inducing excitation of nerve and muscle cells, which are setting the limits used by most generally accepted exposure guidelines, such as the ones published by the International Commission on Non-Ionizing Radiation Protection. In response to a variety of physiological and environmental factors, including heat, cells activate an ancient signaling pathway leading to the transient expression of heat shock proteins (HSPs), which exhibit sophisticated protection mechanisms. A number of studies suggest that also ELF-MF exposure can activate the cellular stress response and cause increased HSPs expression, both on the mRNA and the protein levels. In this review, we provide some of the presently available data on cellular responses, especially regarding HSP expression, due to single and combined exposure to ELF-MF and heat, with the aim to compare the induced effects and to detect possible common modes of action. Some evidence suggest that MF and heat can act as costressors inducing a kind of thermotolerance in cell cultures and in organisms. The MF exposure might produce a potentiated or synergistic biological response such as an increase in HSPs expression, in combination with a well-defined stress, and in turn exert beneficial effects during certain circumstances.