Non-thermal effects of radiofrequency electromagnetic fields Author: Peter Wust1, Benedikt Kortüm2, Ulf Strauss3, Jacek Nadobny4, Sebastian Zschaeck4,5, Marcus Beck4, Ulrike Stein2,6, Pirus Ghadjar4 Affiliation: <sup>1</sup> Department of Radiation Oncology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Augustenburger Platz 1, 13353, Berlin, Germany. peter.wust@charite.de. <sup>2</sup> Experimental and Clinical Research Center, Charité-Universitätsmedizin Berlin and Max-Delbrück-Centrum (MDC), Robert-Rössle-Str. 10, 13092, Berlin, Germany. <sup>3</sup> Institute of Cellbiology and Neurobiology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Charitéplatz 1, 10117, Berlin, Germany. <sup>4</sup> Department of Radiation Oncology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Augustenburger Platz 1, 13353, Berlin, Germany. <sup>5</sup> Berlin Institute of Health (BIH), Anna-Louisa-Karsch Str. 2, 10178, Berlin, Germany. <sup>6</sup> German Cancer Consortium (DKTK), Im Neuenheimer Feld 280, 69120, Heidelberg, Germany. Conference/Journal: Sci Rep Date published: 2020 Aug 10 Other: Volume ID: 10 , Issue ID: 1 , Pages: 13488 , Special Notes: doi: 10.1038/s41598-020-69561-3. , Word Count: 167 We explored the non-thermal effects of radiofrequency (RF) electromagnetic fields and established a theoretical framework to elucidate their electrophysiological mechanisms. In experiments, we used a preclinical treatment device to treat the human colon cancer cell lines HT-29 and SW480 with either water bath heating (WB-HT) or 13.56 MHz RF hyperthermia (RF-HT) at 42 °C for 60 min and analyzed the proliferation and clonogenicity. We elaborated an electrical model for cell membranes and ion channels and estimated the resulting ion fluxes. The results showed that, for both cell lines, using RF-HT significantly reduced proliferation and clonogenicity compared to WB-HT. According to our model, the RF electric field component was rectified and smoothed in the direction of the channel, which resulted in a DC voltage of ~ 1 µV. This may induce ion fluxes that can potentially cause relevant disequilibrium of most ions. Therefore, RF-HT creates additional non-thermal effects in association with significant ion fluxes. Increasing the understanding of these effects can help improve cancer therapy. PMID: 32778682 PMCID: PMC7417565 DOI: 10.1038/s41598-020-69561-3