Evaluation of mitochondrial stress following ultraviolet radiation and 5G radiofrequency field exposure in human skin cells

Abstract

Evaluation of mitochondrial stress following ultraviolet radiation and 5G radiofrequency field exposure in human skin cells Patrignoni L, Hurtier A, Orlacchio R, Joushomme A, Poulletier de Gannes F, Lévêque P, Arnaud-Cormos D, Revzani HR, Mahfouf W, Garenne A, Percherancier Y, Lagroye I. Evaluation of mitochondrial stress following ultraviolet radiation and 5G radiofrequency field exposure in human skin cells. Bioelectromagnetics. 2023 Dec 19. doi: 10.1002/bem.22495. Highlights • A 24 h exposure to a 5G signal at 3.5 GHz was able to statistically significantly alter the mitochondrial reactive oxygen species (ROS) production in human skin fibroblasts (decrease at 1 W/Kg) and in human keratinocytes after UV-B irradiation (increase at 0.25 and 1 W/kg). • A 24 h exposure to a 5G signal at 3.5 GHz was not able to alter cell viability, apoptosis and mitochondrial membrane potential in human skin cells, either alone or after UV-B irradiation. • Further studies on 3D or in vivo skin models would be needed to conclude about a possible effect of 5G 3.5 GHz signal on ROS production. Abstract Whether human cells are impacted by environmental electromagnetic fields (EMF) is still a matter of debate. With the deployment of the fifth generation (5G) of mobile communication technologies, the carrier frequency is increasing and the human skin becomes the main biological target. Here, we evaluated the impact of 5G- modulated 3.5 GHz radiofrequency (RF) EMF on mitochondrial stress in human fibroblasts and keratinocytes that were exposed for 24 h at specific absorption rate of 0.25, 1, and 4 W/kg. We assessed cell viability, mitochondrial reactive oxygen species (ROS) production, and membrane polarization. Knowing that human skin is the main target of environmental ultraviolet (UV), using the same read-out, we investigated whether subsequent exposure to 5G signal could alter the capacity of UV-B to damage skin cells. We found a statistically significant reduction in mitochondrial ROS concentration in fibroblasts exposed to 5G signal at 1 W/kg. On the contrary, the RF exposure slightly but statistically significantly enhanced the effects of UV-B radiation specifically in keratinocytes at 0.25 and 1 W/kg. No effect was found on mitochondrial membrane potential or apoptosis in any cell types or exposure conditions suggesting that the type and amplitude of the observed effects are very punctual. pubmed.ncbi.nlm.nih.gov Excerpts To our knowledge, only a few published articles have examined the effects of 5G technology in experimental studies (EMF-Portal, 2022) at the specific band of 3.5 GHz. Among these, the exposure of zebrafish embryos at specific absorption rate (SAR) of 8.27 W/kg induced depressed sensorimotor function, abnormal behavioral responses, and variations in the expression of genes related to metabolic function in adult zebrafish (Dasgupta et al., 2020, 2022). In Drosophila melanogaster, 3.5 GHz exposure enhanced the expression of heat shock, oxidative stress, and humoral immunity system genes leading to fly developmental promotion (Wang et al., 2022). In addition, long-term exposure resulted in alterations of the expression of circadian clock genes resulting in improvement of sleep duration (Wang et al., 2021). Exposure of diabetic and healthy rats brains revealed an increase in appetite, energy metabolism, and oxidative stress (Bektas et al., 2022). Finally, no effect on anxiety- like behavior, but a SAR-dependent increase in different oxidative stress parameters were found in the guinea pig auditory cortex (Yang et al., 2022). Unfortunately, all these studies are highly heterogeneous in terms of endpoints, biological systems, and SAR levels, making it impossible to draw firm conclusions about the effects of 3.5 GHz signals on human health. It is also essential to indicate that all these studies used either an unmodulated or a GSM-modulated 3.5 GHz signal, but none of them used a 5G-modulated signal. In addition, none of the above-mentioned studies addressed the skin or other superficial tissues as relevant targets. Actually, since the penetration of the RF-EMF into the tissues decreases as the frequency increases, and given the large amount of water in the skin (Christ et al., 2006; Feldman et al., 2009), this tissue is susceptible to absorb most of the RF- EMF power when exposed to the 5G highest frequency ranges, that is, at 3.5 GHz and even more at 26 GHz.... Exposure of cells to 5G-modulated signals at 3.5 GHz was performed using an innovative reverberation chamber (RC) (Orlacchio et al., 2023), that is, an electrically large cavity made of metallic walls where a homogeneous field distribution was achieved through random mechanical stirring of the field components (Hill, 1998). This is particularly convenient in bioelectromagnetic experiments to ensure a highly homogeneous exposure level regardless of the samples location within the exposure system (Capstick et al., 2017; Ito & Bassett, 1983). In this study, a cell culture incubator (150 L; BINDER Gmbh), was converted into an RC to guarantee 24 h in vitro exposure under controlled biological conditions (37°C, 5% CO2, and 95% humidity). A detailed description of the system schematically represented in Figure 1a was given in (Orlacchio et al., 2023). The main components are reported hereafter. A printed patch antenna was used to deliver 5G-modulated 3.5 GHz signal in the chamber. A metallic stirrer composed of eight rectangular blades (8 × 10 × 1 cm3) was mounted on a 30 cm mast to continuously rotate through a motorized precision rotation stage (PRM1/MZ8; Thorlabs Inc.) driven via a K-Cube dc servo controller (KDC101; Thorlabs). The continuous rotation modified the boundary conditions during exposure allowing to achieve a homogeneous and isotropic averaged EMF within the samples (Serra et al., 2017).... We report here some effects of 5G-modulated RF-EMF at 3.5 GHz on human skin cells, either alone in human fibroblasts, or after exposure to UV-B radiations in human keratinocytes. The effects were found nonlinear in relation to the SAR level and their amplitude did not exceed 30% compared to sham (fibroblasts) or to UV-B radiation (keratinocytes). Interestingly, we found no correlation with any change in the UV-B-induced mitochondrial membrane potential or apoptosis, suggesting that the RF-EMF increase in UV-B-induced ROS production was not enough to additionally impact neither mitochondrial membrane potential, apoptosis nor necrosis. To further determine whether these effects could lead to any protective effect or increase UV-B harmful bioeffects, it would be interesting to evaluate the activation of the cell's antioxidant response, that is, superoxide dismutase, glutathione, or glutathione peroxidase expression level or activity. It will also be of importance to assess whether the presence of ROS can induce end-products, such as 4-hydroxy-2-nonenal that is produced by lipid peroxidation in cells, either in skin's organoids (Sun et al., 2021) or in skin in vivo, as we previously assessed in the sera of rats exposed to a CW 2.45 GHz signal (7 h/day for 30 days, 0.16 W/kg whole- body SAR) (De Gannes et al., 2009). These approaches would indeed be more representative of the skin complexity and take into account the interaction among the different skin cells.

AI evidence extraction

Main findings

Human fibroblasts and keratinocytes were exposed for 24 h to a 5G-modulated 3.5 GHz RF-EMF at SARs of 0.25, 1, and 4 W/kg. A statistically significant reduction in mitochondrial ROS was observed in fibroblasts at 1 W/kg, while RF exposure slightly but statistically significantly enhanced UV-B effects on ROS in keratinocytes at 0.25 and 1 W/kg. No effects were found on mitochondrial membrane potential or apoptosis in any cell type or exposure condition, and the highlights state no alteration of cell viability.

Outcomes measured

• Mitochondrial reactive oxygen species (ROS) production
• Cell viability
• Apoptosis
• Mitochondrial membrane potential (membrane polarization)
• Interaction with UV-B irradiation (subsequent exposure)

Limitations

• In vitro cell culture model (human fibroblasts and keratinocytes)
• Effects described as punctual/nonlinear with SAR and limited amplitude (≤30% vs sham or UV-B)
• Authors note further studies in 3D or in vivo skin models are needed to conclude about possible effects on ROS production
• Sample size not reported in provided text

Suggested hubs

• 5g-policy (0.7)
  Study evaluates a 5G-modulated signal at 3.5 GHz and discusses relevance to 5G deployment and skin as a target.

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    "study_type": "in_vitro",
    "exposure": {
        "band": "RF",
        "source": "5G signal",
        "frequency_mhz": 3500,
        "sar_wkg": null,
        "duration": "24 h"
    },
    "population": "Human skin fibroblasts and keratinocytes (cell cultures)",
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    "outcomes": [
        "Mitochondrial reactive oxygen species (ROS) production",
        "Cell viability",
        "Apoptosis",
        "Mitochondrial membrane potential (membrane polarization)",
        "Interaction with UV-B irradiation (subsequent exposure)"
    ],
    "main_findings": "Human fibroblasts and keratinocytes were exposed for 24 h to a 5G-modulated 3.5 GHz RF-EMF at SARs of 0.25, 1, and 4 W/kg. A statistically significant reduction in mitochondrial ROS was observed in fibroblasts at 1 W/kg, while RF exposure slightly but statistically significantly enhanced UV-B effects on ROS in keratinocytes at 0.25 and 1 W/kg. No effects were found on mitochondrial membrane potential or apoptosis in any cell type or exposure condition, and the highlights state no alteration of cell viability.",
    "effect_direction": "mixed",
    "limitations": [
        "In vitro cell culture model (human fibroblasts and keratinocytes)",
        "Effects described as punctual/nonlinear with SAR and limited amplitude (≤30% vs sham or UV-B)",
        "Authors note further studies in 3D or in vivo skin models are needed to conclude about possible effects on ROS production",
        "Sample size not reported in provided text"
    ],
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    "confidence": 0.7800000000000000266453525910037569701671600341796875,
    "peer_reviewed_likely": "yes",
    "keywords": [
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        "radiofrequency",
        "RF-EMF",
        "human skin cells",
        "fibroblasts",
        "keratinocytes",
        "mitochondrial stress",
        "reactive oxygen species",
        "ROS",
        "apoptosis",
        "mitochondrial membrane potential",
        "UV-B",
        "reverberation chamber",
        "SAR"
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