Avis de soutenance - doctorat - Lorenza PATRIGNONI

“Bioelectromagnetism” combines the biological and physical fields of research, with the aim to assess the mechanisms by which electromagnetic waves interact with living tissues, potentially associated with beneficial or deleterious effects. During the past two decades, this discipline has shown increasing interest given the development in electromagnetic fields (EMF) emitting technologies and its public concern. Sources of man-made EMF are medical devices (e.g., magnetic resonance imaging), electrical equipment, micro-wave oven, antennas for broadcasting radiofrequency (RF) power, or general public technologies such as mobile and wireless communication, and data transmission. Mobile phones are a particular source of EMF that has rapidly grown in a few years, and that will continue to grow in the next future. To support this development, several generations of communication technologies have succeeded one another from the end of the twentieth century to today. The fifth generation (5G), the last one, was developed to fix network congestion, support media traffic, and provide news services to the society. All mobile communication technologies belong to the RF range, which runs between 10 MHz and 300 GHz in the electromagnetic spectrum. RF fields are described as non-ionizing radiations since they carry little energy quantities (photons), below the value of 12 eV, which is commonly required to ionize the living material. In particular, the 5G technology will operate at three frequency bands: 700 MHz, 3.5 GHz, and up to the 26 GHz band. For now, the only well-described effect of RF on biological systems is known to be caused by the dielectric relaxation-related tissue heating, on which lie standards for exposure limits. The hypothesis that, environmental RF exposure may induce deleterious effects through the activation of cellular stress, such as apoptosis or oxidative stress response through increased production of reactive oxygen species (ROS), has been widely evaluated. Unfortunately, those results are variable and contradictory. On the other hand, very few information is available on the possible activation of another very sensitive stress signaling pathway linked to the accumulation of misfolded proteins: the endoplasmic reticulum (ER) unfolded protein response (UPR). The aim of my PhD research was to investigate the impact of the new 5G RF signal at 3.5 GHz on mitochondrial and ER stress, in human skin fibroblasts and keratinocytes cells. The choice of skin biologic model is related to the fact that RF absorption within the tissues is decreasing while the frequency increases, making skin one of the main target tissues of RF. The cells were exposed to RF for 24 hours at three different specific absorption rates (SAR): 0.25, 1, and 4 W/kg. In some set of experiments, cells were pre-irradiated with UV-B in order to investigate the possibility for an interaction between the two physical environmental agents. The results suggested that 5G modulated radiofrequency at 3.5 GHz, alone or in co-exposure with UV-B, could modulate mitochondrial ROS generation in a cell-specific manner. However, this had no impact on mitochondrial function in terms of membrane potential nor on cell viability, suggesting that the level of ROS was not sufficiently high (no oxidative burst). Finally, the study on the expression of a panel of genes specifically related to ER-stress and apoptosis showed no differentially-expressed genes in human primary fibroblasts, whatever the exposure set-up. In conclusion, exposure to a 5G RF signal at 3.5 GHz and up to 4 W/kg induced only small changes in ROS production, differently according to cell types, in the presence or absence of UV-B. These changes had no further impact on cell viability. Moreover, the lack of differential expression in genes related to the UPR suggesting that the ER is not sensitive to RF exposure.