Effects of radiofrequency fields on RAS and ERK kinases activity in live cells using the bioluminescence resonance energy transfer technique

Abstract

Purpose: The present study was conducted to re-evaluate the effect of low-level 1800 MHz RF signals on RAS/MAPK activation in live cells.

Material and methods: Using Bioluminescence Resonance Energy Transfer technique (BRET), we assessed the effect of Continuous wave (CW) and Global System for Mobile (GSM)-modulated 1800 MHz signals (up to 2 W/kg) on ERK and RAS kinases' activity in live HuH7 cells.

Results: We found that radiofrequency field (RF) exposure for 24 h altered neither basal level of RAS and ERK activation nor the potency of phorbol-12-myristate-13-acetate (PMA) to activate RAS and ERK kinases. However, we found that exposure to GSM-modulated 1800 MHz signals at 2 W/kg decreased the PMA maximal efficacy to activate both RAS and ERK kinases' activity. Exposure with CW 1800 MHz signal at 2 W/kg only decreased maximal efficacy of PMA to activate ERK but not RAS. No effects of RF exposure at 0.5 W/kg was observed on maximal efficacy of PMA to activate either RAS or ERK whatever the signal used.

Conclusions: Our results indicate that RF exposure decreases the efficiency of the cascade of events, which, from the binding of PMA to its receptor(s), leads to the activation of RAS and ERK kinases.

Keywords:

• Radiofrequency fields
• BRET
• kinases
• phorbol ester
• adaptive response

Acknowledgments

We thank Bernard Veyret for his wise advice and proofreading of the manuscript.

Author contributions

YP conceived and designed the study. PL and DAC designed the device and performed the electromagnetic dosimetry. EP, LP, HJR, FPDG, AH, RR, and YP collected and assembled the data. AG performed the statistical analysis of the results. YP, IL, DAC, and PL wrote the manuscript. All coauthors read and approved the final manuscript.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

The research leading to these results received funding from the European Community’s Seventh Framework Program (FP7/2007–2013) under grant agreement no. [603794] (the GERONIMO project). This study was performed within the framework of COST action EMF-MED [BM1309] supported by European Cooperation in Science and Technology (COST). This work was also supported by FP7 Environment.

Notes on contributors

Emmanuelle Poque

Emmanuelle Poque is a Biologist Engineer at the Polytechnic Institute of Bordeaux (Bordeaux INP), working on bioelectromagnetics at the cellular and molecular levels.

Delia Arnaud-Cormos

Delia Arnaud-Cormos, PhD, is an Associate Professor in the Xlim Research Institute, University of Limoges, France. Since 2018, she is a junior member of the Institut Universitaire de France (IUF). Her research interests concern nanosecond pulses/microwave exposure systems set-up and dosimetric characterization for bioelectromagnetic studies.

Lorenza Patrignoni

Lorenza Patrignoni, MPharm, is a master's student working on bioelectromagnetics at the cellular and molecular levels.

Hermanus J. Ruigrok

Hermanus J. Ruigrok, PhD, is a post-doctoral researcher working on bioelectronics.

Florence Poulletier De Gannes

Florence Poulletier de Gannes, PhD, is a CNRS research engineer at the IMS laboratory. Her research deals mainly with the adverse and beneficial biological effects of non-invasive electromagnetic fields funded by several national and foreign programmes. She also works on EMF health risk assessment.

Annabelle Hurtier

Annabelle Hurtier is a Bordeaux INP Biologist Technician at the IMS laboratory. She is in charge of animal facility and is a specialist in animal welfare.

Rémy Renom

Rémy Renom, Master degree, is a Biologist Engineer working on bioelectromagnetics at the cellular and molecular levels.

André Garenne

André Garenne, PharmD, PhD, is an Associate Professor and Researcher at CNRS UMR 5293 (IMN). He is working at Bordeaux University (France). His main research domains are computational neuroscience, statistics, neural data analysis and machine learning.

Isabelle Lagroye

Isabelle Lagroye, PhD, is a Director of studies at the Ecole Pratique des Hautes Etudes (EPHE) working at Bordeaux University, France. Her research deals mainly with the biological and toxicological effects of non-invasive electromagnetic fields. She is currently member of the Bruxelles-Capitale expert committee on non-ionising radiations.

Philippe Lévêque

Philippe Lévêque, PhD, is a CNRS Senior Scientist and the group leader of the BioEM group working on nanopulse applications in the XLIM Research Institute, University of Limoges. He is involved in the development of dosimetry and exposure setups for health-risk assessment in cooperation with biological and medical research groups.

Yann Percherancier

Yann Percherancier, PhD, is a CNRS Senior Scientist and is working at Bordeaux University (France). His main research focus on deciphering the effects of low-level electromagnetic fields on living matter at the cellular and molecular level.