Department of Radiation Oncology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
Experimental and Clinical Research Center, Charité - Universitätsmedizin Berlin and Max-Delbrück-Centrum (MDC), Berlin, Germany.
Int J Hyperthermia. 2021;38(1):715-731. doi: 10.1080/02656736.2021.1914354.
The temperature-independent effects of electromagnetic fields (EMF) have been controversial for decades. Here, we critically analyze the available literature on non-thermal effects of radiofrequency (RF) and microwave EMF. We present a literature review of preclinical and clinical data on non-thermal antiproliferative effects of various EMF applications, including conventional RF hyperthermia (HT, cRF-HT). Further, we suggest and evaluate plausible biophysical and electrophysiological models to decipher non-thermal antiproliferative membrane effects. Available preclinical and clinical data provide sufficient evidence for the existence of non-thermal antiproliferative effects of exposure to cRF-HT, and in particular, amplitude modulated (AM)-RF-HT. In our model, transmembrane ion channels function like RF rectifiers and low-pass filters. cRF-HT induces ion fluxes and AM-RF-HT additionally promotes membrane vibrations at specific resonance frequencies, which explains the non-thermal antiproliferative membrane effects ion disequilibrium (especially of Ca) and/or resonances causing membrane depolarization, the opening of certain (especially Ca) channels, or even hole formation. AM-RF-HT may be tumor-specific owing to cancer-specific ion channels and because, with increasing malignancy, membrane elasticity parameters may differ from that in normal tissues. Published literature suggests that non-thermal antiproliferative effects of cRF-HT are likely to exist and could present a high potential to improve future treatments in oncology.
电磁场（EMF）的温度独立效应已经争论了几十年。在这里，我们批判性地分析了关于射频（RF）和微波 EMF 的非热效应的现有文献。我们对各种 EMF 应用的非热抗增殖作用的临床前和临床数据进行了文献回顾，包括常规 RF 热疗（HT，cRF-HT）。此外，我们提出并评估了合理的生物物理和电生理模型，以破译非热抗增殖膜效应。现有的临床前和临床数据为接触 cRF-HT（特别是调幅（AM）-RF-HT）暴露存在非热抗增殖作用提供了充分的证据。在我们的模型中，跨膜离子通道的功能类似于 RF 整流器和低通滤波器。cRF-HT 诱导离子通量，AM-RF-HT 另外还会在特定共振频率下促进膜振动，这解释了非热抗增殖膜效应——离子失衡（特别是 Ca）和/或导致膜去极化的共振、某些（特别是 Ca）通道的打开，甚至孔形成。由于肿瘤特异性离子通道的存在，以及随着恶性程度的增加，细胞膜弹性参数可能与正常组织不同，AM-RF-HT 可能具有肿瘤特异性。已发表的文献表明，cRF-HT 的非热抗增殖作用可能存在，并有可能为肿瘤学未来的治疗提供很高的潜力。
