Ziemann, ChristinaChristinaZiemannTillmann, ThomasThomasTillmannOertel, AntjeAntjeOertelBrockmeyer, HeidrunHeidrunBrockmeyerMurbach, M.M.MurbachCapstick, M.M.CapstickKuster, N.N.KusterDasenbrock, ClemensClemensDasenbrock2022-03-042022-03-042013https://publica.fraunhofer.de/handle/publica/234311Public exposure to radiofrequency electromagnetic fields (RF-EMF) has increased dramatically, attracting attention to health risk evaluation. RF-EMF was classified as possibly carcinogenic to humans (Group 2B) by the IARC in 2011, but clear risk assessment is still limited by data gaps and contradictory results. As there are hints of disturbance of DNA-integrity by RF-EMF exposure, we investigated the in vitro and in vivo genotoxic and co-genotoxic potential of intermittent exposure (5 min ON/10 min OFF) to different RF-EMF signals (continuous wave, UMTS, WiFi, RFID), using well established and standardized genotoxicity tests. In vitro, normal human MRC-5 lung fibroblasts were exposed blinded in two parallel waveguides (1 sham, 1 exposed) of a 1950 MHz exposure system for 1, 4, or 24h to specific absorption rates (SAR) of 0.5, 2.0, or 4.92 W/kg. Induction of DNA-strand breaks (DSB) and oxidative DNA-damage was subsequently evaluated in an enzyme (hOGG1)-modified comet assay. In vivo, male B6C3F1 mice were whole-body exposed at SAR of 1.6, 4.0 and 10 W/kg for 14d (20h/d) using a reverberation chamber. Micronucleus (MN) frequency was determined in peripheral blood (PB) and immature bone marrow erythrocytes, and in keratinocytes. Furthermore, malondialdehyde (MDA) was measured in PB erythrocytes. Irrespective of signal type, SAR, or exposure duration the RF-EMF signals didn't mediate significant cytotoxicity, induction of DSB or oxidative DNA-damage in MRC-5 cells, compared to sham-exposed cells. This was confirmed in human HTR-8/SVneo trophoblast cells. But, the positive controls EMS (DSB) and potassium bromate (oxidative DNA-damage) were quite effective, indicating appropriate sensitivity of the cells and accurate performance of the test. In vivo, no significant increase in MN formation was observed in CW, WiFi, or RFID exposed mice. However, slight, but significant increase in MN was obvious in PB erythrocytes after UMTS (10 W/kg) exposure, the clastogenic activity of cyclophosphamide was significantly decreased by CW pre-exposure (10 W/kg) in bone marrow, and MDA levels were altered by WiFi and RFID. In conclusion, none of the tested RF-EMF signals revealed evidence for a marked direct DNA-damaging potential in vitro. There are, however, indications of slight RF-EMF-mediated effects in vivo, which need to be confirmed. Part of the SEAWIND project, funded by the European Union's Seventh Framework Programme ([FP7/2007-2013)] under grant agreement No. 244149en615journal article