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.

Nanometer-Scale Permeabilization and Osmotic Swelling Induced by 5-ns Pulsed Electric Fields.

High-intensity nanosecond pulsed electric fields (nsPEFs) permeabilize cell membranes. Although progress has been made toward an understanding of the mechanism of nsPEF-induced membrane poration, the dependence of pore size and distribution on pulse duration, strength, number, and repetition rate remains poorly defined experimentally. In this paper, we characterize the size of nsPEF-induced pores in living cell membranes by isosmotically replacing the solutes in pulsing media with polyethylene glycols and sugars before exposing Jurkat T lymphoblasts to 5 ns, 10 MV/m electric pulses. Pore size was evaluated by analyzing cell volume changes resulting from the permeation of osmolytes through the plasma membrane. We find that pores created by 5 ns pulses have a diameter between 0.7 and 0.9 nm at pulse counts up to 100 with a repetition rate of 1 kHz. For larger number of pulses, either the pore diameter or the number of pores created, or both, increase with increasing pulse counts. But the prevention of cell swelling by PEG 1000 even after 2000 pulses suggests that 5 ns, 10 MV/m pulses cannot produce pores with a diameter larger than 1.9 nm.

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.

Dysbindin-1 modifies signaling and cellular localization of recombinant, human D3 and D2 receptors.

Dystrobrevin binding protein-1 (dysbindin-1), a candidate gene for schizophrenia, modulates cognition, synaptic plasticity and frontocortical circuitry and interacts with glutamatergic and dopaminergic transmission. Loss of dysbindin-1 modifies cellular trafficking of dopamine (DA) D2 receptors to increase cell surface expression, but its influence upon signaling has never been characterized. Further, the effects of dysbindin-1 upon closely related D3 receptors remain unexplored. Hence, we examined the impact of dysbindin-1 (isoform A) co-expression on the localization and coupling of human D2L and D3 receptors stably expressed in Chinese hamster ovary or SH-SY5Y cells lacking endogenous dysbindin-1. Dysbindin-1 co-transfection decreased cell surface expression of both D3 and D2L receptors. Further, while their affinity for DA was unchanged, dysbindin-1 reduced the magnitude and potency of DA-induced adenylate cylase recruitment/cAMP production. Dysbindin-1 also blunted the amplitude of DA-induced phosphorylation of ERK1/2 and Akt at both D2L and D3 receptors without, in contrast to cAMP, affecting the potency of DA. Interference with calveolin/clathrin-mediated processes of internalization prevented the modification by dysbindin-1 of ERK1/2 and adenylyl cyclase stimulation at D2L and D3 receptors. Finally, underpinning the specificity of the influence of dysbindin-1 on D2L and D3 receptors, dysbindin-1 did not modify recruitment of adenylyl cyclase by D1 receptors. These observations demonstrate that dysbindin-1 influences cell surface expression of D3 in addition to D2L receptors, and that it modulates activation of their signaling pathways. Accordingly, both a deficiency and an excess of dysbindin-1 may be disruptive for dopaminergic transmission, supporting its link to schizophrenia and other CNS disorders. Dysbindin-1, a candidate gene for schizophrenia, alters D2 receptors cell surface expression. We demonstrate that dysbindin-1 expression also influences cell surface levels of D3 receptors. Further, Dysbindin-1 reduces DA-induced adenylate cylase recruitment/cAMP production and modifies major signaling pathways (Akt and extracellular signal-regulated kinases1/2 (ERK1/2)) of both D2 and D3 receptors. Dysbindin-1 modulates thus D2 and D3 receptor signaling, supporting a link to schizophrenia.

Induced movements of giant vesicles by millimeter wave radiation.

Our previous study of interaction between low intensity radiation at 53.37GHz and cell-size system - such as giant vesicles - indicated that a vectorial movement of vesicles was induced. This effect among others, i.e. elongation, induced diffusion of fluorescent dye di-8-ANEPPS, and increased attractions between vesicles was attributed to the action of the field on charged and dipolar residues located at the membrane-water interface. In an attempt to improve the understanding on how millimeter wave radiation (MMW) can induce this movement we report here a real time evaluation of changes induced on the movement of giant vesicles. Direct optical observations of vesicles subjected to irradiation enabled the monitoring in real time of the response of vesicles. Changes of the direction of vesicle movement are demonstrated, which occur only during irradiation with a "switch on" of the effect. This MMW-induced effect was observed at a larger extent on giant vesicles prepared with negatively charged phospholipids. The monitoring of induced-by-irradiation temperature variation and numerical dosimetry indicate that the observed effects in vesicle movement cannot be attributed to local heating.

Water influx and cell swelling after nanosecond electropermeabilization.

Pulsed electric fields are used to permeabilize cell membranes in biotechnology and the clinic. Although molecular and continuum models provide compelling representations of the mechanisms underlying this phenomenon, a clear structural link between the biomolecular transformations displayed in molecular dynamics (MD) simulations and the micro- and macroscale cellular responses observed in the laboratory has not been established. In this paper, plasma membrane electropermeabilization is characterized by exposing Jurkat T lymphoblasts to pulsed electric fields less than 10ns long (including single pulse exposures), and by monitoring the resulting osmotically driven cell swelling as a function of pulse number and pulse repetition rate. In this way, we reduce the complexity of the experimental system and lay a foundation for gauging the correspondence between measured and simulated values for water and ion transport through electropermeabilized membranes. We find that a single 10MV/m pulse of 5ns duration produces measurable swelling of Jurkat T lymphoblasts in growth medium, and we estimate from the swelling kinetics the ion and water flux that follows the electropermeabilization of the membrane. From these observations we set boundaries on the net conductance of the permeabilized membrane, and we show how this is consistent with model predictions for the conductance and areal density of nanoelectropulse-induced lipid nanopores.

Effect of millimetre waves on phosphatidylcholine membrane models: a non-thermal mechanism of interaction.

The nonthermal biological effects of millimeter waves have been mainly attributed to the interaction with biological membranes. Several data on biomimetic membrane systems seem to support this conclusion. In this paper a mechanistic hypothesis is evaluated to explain such an interaction taking into account experimental NMR data on deuterium-labeled phospholipid vesicles. These data showed that millimeter waves induce a time and a hydration-dependent reduction of the water ordering around the phosphocholine headgroups. This effect is here interpreted as a change in membrane water partitioning, due to the coupling of the radiation with the fast rotational dynamics of bound water molecules, that results in a measurable relocation of water molecules from the inner to the outer binding regions of the membrane interface. When millimeter wave exposure is performed in the vicinity of the transition point, this effect can lead to an upward shift of the membrane phase transition temperature from the fluid to the gel phase. At a macroscopic level, this unique sensitivity may be explained by the universal dynamic behaviour of the membranes in the vicinity of the transition point, where a pretransitional increase of membrane area fluctuations, i.e., of the mean area per phospholipid headgroup, is observed. Exposure to millimeter waves increases the above fluctuations and enhances the second order character of the transition.

Eyes as gateways for environmental light to the substantia nigra: relevance in Parkinson's disease.

Recent data indicates that prolonged bright light exposure of rats induces production of neuromelanin and reduction of tyrosine hydroxylase positive neurons in the substantia nigra. This effect was the result of direct light reaching the substantia nigra and not due to alteration of circadian rhythms. Here, we measured the spectrum of light reaching the substantia nigra in rats and analysed the pathway that light may take to reach this deep brain structure in humans. Wavelength range and light intensity, emitted from a fluorescent tube, were measured, using a stereotaxically implanted optical fibre in the rat mesencephalon. The hypothetical path of environmental light from the eye to the substantia nigra in humans was investigated by computed tomography and magnetic resonance imaging. Light with wavelengths greater than 600 nm reached the rat substantia nigra, with a peak at 709 nm. Eyes appear to be the gateway for light to the mesencephalon since covering the eyes with aluminum foil reduced light intensity by half. Using computed tomography and magnetic resonance imaging of a human head, we identified the eye and the superior orbital fissure as possible gateways for environmental light to reach the mesencephalon.

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.

Radiofrequency radiation at 1950 MHz (UMTS) does not affect key cellular endpoints in neuron-like PC12 cells.

In this study, rat pheochromocytoma (PC12) cells were exposed, as a model of neuron-like cells, to 1950 MHz radiofrequency (RF) radiation with a signal used by the 3G wireless technology of the Universal Mobile Telecommunications System (UMTS) to assess possible adverse effects. RF exposure for 24 h at a specific absorption rate (SAR) of 10 W/kg was carried out in a waveguide system under accurately controlled environmental and dosimetric parameters. DNA integrity, cell viability, and apoptosis were investigated as cellular endpoints relevant for carcinogenesis and other diseases of the central nervous system. Very sensitive biological assays were employed to assess the effects immediately after RF exposure and 24 h later, as demonstrated by the cellular response elicited in PC12 cells using positive control treatments provided for each assay. In our experimental conditions, 24 h of RF exposure at a carrier frequency and modulation scheme typical of a UMTS signal was not able to elicit any effect in the selected cellular endpoints in undifferentiated PC12 cells, despite the application of a higher SAR value than those applied in the majority of the studies reported in the literature.

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.

A positive charge at the N-terminal segment of Discrepin increases the blocking effect of K+ channels responsible for the IA currents in cerebellum granular cells.

Discrepin is a scorpion peptide that blocks preferentially the IA currents of the voltage-dependent K+ channel of rat cerebellum granular cells. It was isolated from the venom of the buthid scorpion Tityus discrepans and contains 38 amino acid residues with a pyroglutamic acid at the N-terminal site. Discrepin has the lowest sequence identity (approx. 50%) among the six members of the alpha-KTx15 sub-family of scorpion toxins. In order to find out which residues are important for the blocking effects of Discrepin, six mutants were chemically synthesized (V6K, I19R, D20K, T35V, I19R-D20K, I19R-D20K-R21V), correctly folded and their physiological properties were examined. Substitution of residues V6 and D20 for basically charged amino acids increases the blocking activity of Discrepin, specially the mutation V6K at the N-terminal segment of the toxin. Analysis of 3D-structure models of the mutants V6K and D20K supports the idea that basic residues improve their blocking activities, similarly to what happens with BmTx3, a toxic peptide obtained from Buthus martensi scorpion, which has the highest known blocking effects of IA currents in K+ channels of rat cerebellum granular cells.

Scorpion toxins that block transient currents (I(A)) of rat cerebellum granular cells.

This communication is a revision of the state-of-the-art knowledge of the field of scorpion toxins specific for the K(+)-channels, responsible for the I(A) currents of granular cells of rat cerebellum, maintained in vitro culture. There are 6 members of the sub-family alpha-KTx15 known to affect the I(A) currents. They are: toxins Aa1 from Androctonus australis Garzoni, BmTx3 from Buthusmartensi Karch, AmmTx3 from Androctonus mauretanicus mauretanicus, AaTx1 and AaTx2 from A. australis Garzoni and Discrepin from Tityus discrepans. They share high sequence similarity, apart from Discrepin, which causes an irreversible effect on the I(A) currents and is the most thoroughly studied toxin of the sub-family alpha-KTx15. The three-dimensional structure of Discrepin was determined and a series of mutants were synthesized and assayed in the system with the aim of identifying possible amino acids or sequence segments responsible for the irreversible effect found. In this revision some unpublished original data are also included to foster future work on the field, as well as a short discussion on some relevant aspects still pending and possible limitations associated with the strategy proposed.

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.

ns Pulsed Electric Field-Induced Action Potentials in the Circuital Model of an Axon.

Pulsed electric fields with duration in the sub- and ns time scale (nsPEFs) increase the permeability of cell membranes, enabling the transport of normally impermeant molecules into or out of the cell (electroporation). Such effect is associated to intracellular alterations and indicates nsPEFs as a new stimulus to modulate cell functions. In particular, studies dealing with the application of nsPEFs to excitable cells suggest their use for the stimulation/inhibition of cell excitation. In this paper, the circuital model per surface unit of the plasma membrane of an axon was developed to implement the Hodgkin and Huxley equations, describing the action potential activation process. For the first time, a power electronics circuital simulator was adopted. The model was first validated with conventional microsecond stimuli, and then it was employed to identify the conditions for cell excitation by nsPEFs. The results demonstrated the possibility of electrostimulation by nsPEFs at depolarization levels far below those required for inducing electroporation, and with ionic current dynamics similar to that induced by conventional stimuli, confirming recent experimental findings. Moreover, by using a power electronics tool, easier integration of the cell modeling with the design and optimization of pulse generation systems can be gained.