Authors: Djuari, M. A. ; Engelke, M.;Reamon-Buettner, S. M.; Ziemann, C.; Bitsch, A.
EUROTOX 2025 Congress, Athens, Greece, 14-17 September 2025.
Abstract
In today’s world, stable, fast, and wide-coverage mobile communication is increasingly important. The latest innovation in this field is the fifth generation of mobile telephony, known as 5G New Radio. A major advancement in 5G technology is the extension of the frequency range from previous generations, known as frequency range 1 (<6 GHz; FR1), to frequency range 2 (FR2) in the millimeter range (24.25 – 52.6 GHz, mmWave). Adverse effects of FR1 have been intensively investigated in the last 30 years, whereas only limited information is available for FR2. Therefore, EU-funded SEAWave project focused on FR2 exposure. The project aims to investigate, among others, adverse biological effects of FR2 on skin cells in vitro. The skin represents the main target organ for potential 5G health effects, due to the low-penetration depth of mmWave. Here, we investigated the effects of mmWave on gene expression changes in low-pigmented primary adult and juvenile epidermal keratinocytes (NHEK) and low-pigmented primary adult epidermal melanocytes (NHEM). Cells were exposed to FR2 in a blinded manner at three power densities, i.e., sham, 3.33 W/m2, or 10 W/m2 for 24 h, before subjected to genome-wide transcriptome analysis using Affymetrix microarray technology.
After 24 hours of exposure, FR2 did not induce any alterations in the expression of melanoma-specific genes, such as BRAF and NRAS, in NHEM, nor in the expression of skin carcinoma-specific genes, such as PTCH1 and NOTCH1, in the NHEKs. However, in the juvenile NHEK transcriptome dataset, some pathways were predicted to be activated at 3.33 W/m2, including mitochondrial dysfunction and sonic hedgehog signaling pathway. Furthermore, some other pathways were predicted to be inhibited, such as factors involved in megakaryocyte development and platelet production, and triacylglycerol biosynthesis at 3.33 W/m2, and renin-angiotensin signaling at 10 W/m2. In NHEM, no significant alterations in gene expression and related pathways were observed.
In conclusion, 24 h of FR2 exposure appeared to both activate and inhibit certain pathways in keratinocytes, but not melanocytes, some of which may be relevant to cell growth in juvenile NHEK. Further analyses will investigate changes in the epigenetic landscape, as a potential response to environmental stress, as well as induction of aneugenicity in the primary skin cell models used.