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Non-ionizing Radiations: Biological Effects and Interaction Mechanisms

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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (31 December 2020) | Viewed by 32905

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Dr. Marcella Reale

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Department of Medical, Oral and Biotechnological Sciences, Unit of Immunodiagnostic and Molecular Pathology, University “G.d’Annunzio”, Via Dei Vestini 31, 66100 Chieti, Italy
Interests: neuroimmunology; inflammation; cytokines; non-neuronal cholinergic system; peripheral biomarkers of neurodegeneration; inflammation/autoimmunity
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Dr. Maria Rosaria Scarfì

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Institute for Electromagnetic Sensing of the Environment, National Research Council, Naples, Italy
Interests: non-ionizing radiation; electromagnetic fields
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Dr. Erica Costantini

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Department of Medicine and Aging Science, University “G. D’Annunzio”, Via dei Vestini, 66100 Chieti, Italy
Interests: inflammation; immunity; neurodegenerative diseases; neuroinflammation; anti-inflammatory effects of natural products; peripheral biomarkers research
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

In the last few decades, a large number of investigations has been devoted to study the effects of non-ionizing radiations (NIR) on biological systems. The aim of such studies has been both to address the potential health risk and to explore their potential use in the biomedical field.

Despite the absence of clear indications on the adverse effects induced by NIR, the International Agency for Research on Cancer classified both extremely low frequency and radiofrequency fields as “possibly carcinogenic to humans” (Group 2B). On the other hand, NIR are currently successfully employed for diagnostic and therapeutic purposes.

Both the beneficial and adverse biological effects of NIR have been evidenced in several experimental conditions, but the proposed interaction mechanisms have not been experimentally validated.

We invite authors to present original research articles as well as review articles that stimulate the continuous effort in comprehension of the molecular and biochemical mechanism by which NIR act on biological systems.

The topics to be covered include but are not limited to:

Biological effects and molecular/cellular mechanisms of NIR;
Combined treatments to NIR and chemical or physical agents in experimental models;
The use of NIR in biology and medicine for diagnostic and therapeutic applications.

We thank you in advance for contributing to this important process.

Prof. Dr. Marcella Reale
Dr. Maria Rosaria Scarfì
Dr. Erica Costantini
Dr. Chiara D’Angelo
Guest Editors

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Published Papers (7 papers)

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Research

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13 pages, 5404 KiB

Open AccessArticle

Effects of Electromagnetic Waves with LTE and 5G Bandwidth on the Skin Pigmentation In Vitro

by Kyuri Kim, Young Seung Lee, Nam Kim, Hyung-Do Choi, Dong-Jun Kang, Hak Rim Kim and Kyung-Min Lim

Int. J. Mol. Sci. 2021, 22(1), 170; https://doi.org/10.3390/ijms22010170 - 26 Dec 2020

Cited by 15 | Viewed by 7395

Abstract

With the rapid growth of wireless communication devices, the influences of electromagnetic fields (EMF) on human health are gathering increasing attention. Since the skin is the largest organ of the body and is located at the outermost layer, it is considered a major target for the health effects of EMF. Skin pigmentation represents one of the most frequent symptoms caused by various non-ionizing radiations, including ultraviolet radiation, blue light, infrared, and extremely low frequency (ELF). Here, we investigated the effects of EMFs with long-term evolution (LTE, 1.762 GHz) and 5G (28 GHz) bandwidth on skin pigmentation in vitro. Murine and Human melanoma cells (B16F10 and MNT-1) were exposed to either LTE or 5G for 4 h per day, which is considered the upper bound of average smartphone use time. It was shown that neither LTE nor 5G exposure induced significant effects on cell viability or pigmentation. The dendrites of MNT-1 were neither lengthened nor regressed after EMF exposure. Skin pigmentation effects of EMFs were further examined in the human keratinocyte cell line (MNT-1-HaCaT) co-culture system, which confirmed the absence of significant hyper-pigmentation effects of LTE and 5G EMFs. Lastly, MelanoDerm™, a 3D pigmented human epidermis model, was irradiated with LTE (1.762 GHz) or 5G (28 GHz), and image analysis and special staining were performed. No changes in the brightness of MelanoDerm™ tissues were observed in LTE- or 5G-exposed tissues, except for only minimal changes in the size of melanocytes. Collectively, these results imply that exposure to LTE and 5G EMFs may not affect melanin synthesis or skin pigmentation under normal smartphone use condition. Full article

(This article belongs to the Special Issue Non-ionizing Radiations: Biological Effects and Interaction Mechanisms)

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14 pages, 4730 KiB

Open AccessArticle

Short ELF-EMF Exposure Targets SIRT1/Nrf2/HO-1 Signaling in THP-1 Cells

by Antonia Patruno, Erica Costantini, Alessio Ferrone, Mirko Pesce, Francesca Diomede, Oriana Trubiani and Marcella Reale

Int. J. Mol. Sci. 2020, 21(19), 7284; https://doi.org/10.3390/ijms21197284 - 2 Oct 2020

Cited by 28 | Viewed by 4411

Abstract

Extremely low frequency electromagnetic fields (ELF-EMFs) have been known to modulate inflammatory responses by targeting signal transduction pathways and influencing cellular redox balance through the generation of oxidants and antioxidants. Here, we studied the molecular mechanism underlying the anti-oxidative effect of ELF-EMF in THP-1 cells, particularly with respect to antioxidant enzymes, such as heme oxygenase-1 (HO-1), regulated transcriptionally through nuclear factor E2-related factor 2 (Nrf2) activation. Cells treated with lipopolysaccharides (LPS) were exposed to a 50 Hz, 1 mT extremely low frequency electromagnetic fields for 1 h, 6 h and, 24 h. Our results indicate that ELF-EMF induced HO-1 mRNA and protein expression in LPS-treated THP-1 cells, with peak expression at 6 h, accompanied with a concomitant migration to the nucleus of a truncated HO-1 protein form. The immunostaining analysis further verified a nuclear enrichment of HO-1. Moreover, ELF-EMF inhibited the protein expressions of the sirtuin1 (SIRT1) and nuclear factor kappa B (NF-kB) pathways, confirming their anti-inflammatory/antioxidative role. Pretreatment with LY294002 (Akt inhibitor) and PD980559 (ERK inhibitor) inhibited LPS-induced Nrf2 nuclear translocation and HO-1 protein expression in ELF-EMF-exposed cells. Taken together, our results suggest that short ELF-EMF exposure exerts a protective role in THP-1 cells treated with an inflammatory/oxidative insult such as LPS, via the regulation of Nrf-2/HO-1 and SIRT1 /NF-kB pathways associated with intracellular glutathione (GSH) accumulation. Full article

(This article belongs to the Special Issue Non-ionizing Radiations: Biological Effects and Interaction Mechanisms)

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24 pages, 3281 KiB

Open AccessArticle

Human Fibroblasts In Vitro Exposed to 2.45 GHz Continuous and Pulsed Wave Signals: Evaluation of Biological Effects with a Multimethodological Approach

by Elisa Regalbuto, Anna Anselmo, Stefania De Sanctis, Valeria Franchini, Florigio Lista, Monica Benvenuto, Roberto Bei, Laura Masuelli, Guglielmo D’Inzeo, Alessandra Paffi, Eugenio Trodella and Antonella Sgura

Int. J. Mol. Sci. 2020, 21(19), 7069; https://doi.org/10.3390/ijms21197069 - 25 Sep 2020

Cited by 12 | Viewed by 3394

Abstract

The increasing exposure to radiofrequency electromagnetic fields (RF-EMF), especially from wireless communication devices, raises questions about their possible adverse health effects. So far, several in vitro studies evaluating RF-EMF genotoxic and cytotoxic non-thermal effects have reported contradictory results that could be mainly due to inadequate experimental design and lack of well-characterized exposure systems and conditions. Moreover, a topic poorly investigated is related to signal modulation induced by electromagnetic fields. The aim of this study was to perform an analysis of the potential non-thermal biological effects induced by 2.45 GHz exposures through a characterized exposure system and a multimethodological approach. Human fibroblasts were exposed to continuous (CW) and pulsed (PW) signals for 2 h in a wire patch cell-based exposure system at the specific absorption rate (SAR) of 0.7 W/kg. The evaluation of the potential biological effects was carried out through a multimethodological approach, including classical biological markers (genotoxic, cell cycle, and ultrastructural) and the evaluation of gene expression profile through the powerful high-throughput next generation sequencing (NGS) RNA sequencing (RNA-seq) approach. Our results suggest that 2.45 GHz radiofrequency fields did not induce significant biological effects at a cellular or molecular level for the evaluated exposure parameters and conditions. Full article

(This article belongs to the Special Issue Non-ionizing Radiations: Biological Effects and Interaction Mechanisms)

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15 pages, 1949 KiB

Open AccessArticle

Bone Morphogenetic Protein-2 Signaling in the Osteogenic Differentiation of Human Bone Marrow Mesenchymal Stem Cells Induced by Pulsed Electromagnetic Fields

by Fernanda Martini, Agnese Pellati, Elisa Mazzoni, Simona Salati, Gaetano Caruso, Deyanira Contartese and Monica De Mattei

Int. J. Mol. Sci. 2020, 21(6), 2104; https://doi.org/10.3390/ijms21062104 - 19 Mar 2020

Cited by 31 | Viewed by 4572

Abstract

Pulsed electromagnetic fields (PEMFs) are clinically used with beneficial effects in the treatment of bone fracture healing. This is due to PEMF ability to favor the osteogenic differentiation of mesenchymal stem cells (MSCs). Previous studies suggest that PEMFs enhance the osteogenic activity of bone morphogenetic protein-2 (BMP2) which is used in various therapeutic interventions. This study investigated the molecular events associated to the synergistic activity of PEMFs and BMP2 on osteogenic differentiation. To this aim, human MSCs (hMSCs) were exposed to PEMFs (75 Hz, 1.5 mT) in combination with BMP2, upon detection of the minimal dose able to induce differentiation. Changes in the expression of BMP signaling pathway genes including receptors and ligands, as well as in the phosphorylation of BMP downstream signaling proteins, such as SMAD1/5/8 and MAPK, were analyzed. Results showed the synergistic activity of PEMFs and BMP2 on osteogenic differentiation transcription factors and markers. The PEMF effects were associated to the increase in BMP2, BMP6, and BMP type I receptor gene expression, as well as SMAD1/5/8 and p38 MAPK activation. These results increase knowledge concerning the molecular events involved in PEMF stimulation showing that PEMFs favor hMSCs osteogenic differentiation by the modulation of BMP signaling components. Full article

(This article belongs to the Special Issue Non-ionizing Radiations: Biological Effects and Interaction Mechanisms)

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13 pages, 3984 KiB

Open AccessArticle

CT2A Cell Viability Modulated by Electromagnetic Fields at Extremely Low Frequency under No Thermal Effects

by Olga García-Minguillán, Raquel Prous, Maria del Carmen Ramirez-Castillejo and Ceferino Maestú

Int. J. Mol. Sci. 2020, 21(1), 152; https://doi.org/10.3390/ijms21010152 - 24 Dec 2019

Cited by 14 | Viewed by 3782

Abstract

The effects produced by electromagnetic fields (EMFs) on human beings at extremely low frequencies (ELFs) have being investigated in the past years, across in vitro studies, using different cell lines. Nevertheless, the effects produced on cells are not clarified, and the cellular mechanisms and cell-signaling processes involved are still unknown. This situation has resulted in a division among the scientific community about the adequacy of the recommended level of exposure. In this sense, we consider that it is necessary to develop long-term exposure studies and check if the recommended levels of EMFs are under thermal effects. Hence, we exposed CT2A cells to different EMFs at different ELFs at short and long times. Our results showed frequency dependence in CT2A exposed during 24 h to a small EMF of 30 μT equal to those originated by the Earth and frequency dependence after the exposure during seven days to an EMF of 100 µT at different ELFs. Particularly, our results showed a remarkable cell viability decrease of CT2A cells exposed to EMFs of 30 Hz. Nevertheless, after analyzing the thermal effects in terms of HSP90 expression, we did not find thermal damages related to the differences in cell viability, so other crucial cellular mechanism should be involved. Full article

(This article belongs to the Special Issue Non-ionizing Radiations: Biological Effects and Interaction Mechanisms)

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Review

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13 pages, 7662 KiB

Open AccessReview

Wound Repair and Extremely Low Frequency-Electromagnetic Field: Insight from In Vitro Study and Potential Clinical Application

by Giulio Gualdi, Erica Costantini, Marcella Reale and Paolo Amerio

Int. J. Mol. Sci. 2021, 22(9), 5037; https://doi.org/10.3390/ijms22095037 - 10 May 2021

Cited by 33 | Viewed by 5186

Abstract

Wound healing is a complex, staged process. It involves extensive communication between the different cellular constituents of various compartments of the skin and its extracellular matrix (ECM). Different signaling pathways are determined by a mutual influence on each other, resulting in a dynamic and complex crosstalk. It consists of various dynamic processes including a series of overlapping phases: hemostasis, inflammation response, new tissue formation, and tissue remodeling. Interruption or deregulation of one or more of these phases may lead to non-healing (chronic) wounds. The most important factor among local and systemic exogenous factors leading to a chronic wound is infection with a biofilm presence. In the last few years, an increasing number of reports have evaluated the effects of extremely low frequency (ELF) electromagnetic fields (EMFs) on tissue repair. Each experimental result comes from a single element of this complex process. An interaction between ELF-EMFs and healing has shown to effectively modulate inflammation, protease matrix rearrangement, neo-angiogenesis, senescence, stem-cell proliferation, and epithelialization. These effects are strictly related to the time of exposure, waveform, frequency, and amplitude. In this review, we focus on the effect of ELF-EMFs on different wound healing phases. Full article

(This article belongs to the Special Issue Non-ionizing Radiations: Biological Effects and Interaction Mechanisms)

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13 pages, 1941 KiB

Open AccessReview

30 Hz, Could It Be Part of a Window Frequency for Cellular Response?

by Olga García-Minguillán and Ceferino Maestú

Int. J. Mol. Sci. 2021, 22(7), 3642; https://doi.org/10.3390/ijms22073642 - 31 Mar 2021

Cited by 6 | Viewed by 2662

Abstract

Many exogenous and endogenous risk factors have been proposed as precursors of brain tumors, including the exposure to non-ionizing electromagnetic fields. Nevertheless, there is still a debate among the scientific community about the hazard of the effects produced by non-ionizing radiation (NIR) because conflicting results have been found (number of articles reviewed >50). For that reason, to provide new evidence on the possible effects produced by exposure to NIR, we performed different studies with several combinations of extremely low frequencies, times, and field intensities in tumoral and non-tumoral cells. The results of our studies showed that cell viability was frequency dependent in glioblastoma cells. In fact, our results revealed that a frequency of 30 Hz—or even other frequencies close to 30 Hz—could constitute a window frequency determinant of the cellular response in tumoral and non-tumoral cells. Full article

(This article belongs to the Special Issue Non-ionizing Radiations: Biological Effects and Interaction Mechanisms)

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