Extremely Low-Frequency Magnetic Fields and Redox-Responsive Pathways Linked to Cancer Drug Resistance: Insights from Co-Exposure-Based In Vitro Studies

Abstract

Electrical devices currently used in clinical practice and common household equipments generate extremely low-frequency magnetic fields (ELF-MF) that were classified by the International Agency for Research on Cancer as “possible carcinogenic.” Assuming that ELF-MF plays a role in the carcinogenic process without inducing direct genomic alterations, ELF-MF may be involved in the promotion or progression of cancers. In particular, ELF-MF-induced responses are suspected to activate redox-responsive intracellular signaling or detoxification scavenging systems. In fact, improved protection against oxidative stress and redox-active xenobiotics is thought to provide critical proliferative and survival advantage in tumors. On this basis, an ever-growing research activity worldwide is attempting to establish whether tumor cells may develop multidrug resistance through the activation of essential cytoprotective networks in the presence of ELF fields, and how this might trigger relevant changes in tumor phenotype. This review builds a framework around how the activity of redox-responsive mediators may be controlled by co-exposure to ELF-MF and reactive oxygen species-generating agents in tumor and cancer cells, in order to clarify whether and how such potential molecular targets could help to minimize or neutralize the functional interaction between ELF-MF and malignancies.

Role of Mitochondria in the Oxidative Stress Induced by Electromagnetic Fields: Focus on Reproductive Systems

“…Several studies suggest that ELF-EMFs do not act as initiators in the process of carcinogenesis, because the energy of the radiation is not strong enough to break chemical bonds in biological molecules. However, it has been speculated that the ELF-EMFs could have a role as co-carcinogens in the promotion and progression of cancer [ 15 - 17 ]. Unfortunately, conclusive information about the link between EMF exposure and cancer is difficult to obtain, given the countless reports and papers published over the decades, with different biological models, diverse physical exposure settings, and controversial findings [ 17 ].…”

“…However, it has been speculated that the ELF-EMFs could have a role as co-carcinogens in the promotion and progression of cancer [ 15 - 17 ]. Unfortunately, conclusive information about the link between EMF exposure and cancer is difficult to obtain, given the countless reports and papers published over the decades, with different biological models, diverse physical exposure settings, and controversial findings [ 17 ]. Furthermore, potential confounding factors in the epidemiological analysis still remain an unresolved issue [ 18 ].…”

“…Several reports evaluated also the influence of the ELF magnetic field on the enzymatic and nonenzymatic antioxidant defence systems [ 17 , 54 – 59 ]. Manikonda and colleagues [ 60 ] found that rats exposed to ELF-MF for 90 days continuously showed oxidative stress with an increase in lipid peroxidation end products and altered glutathione (GSH/GSSG) levels in a dose-dependent manner in various regions of the brain.…”

Manmade Electromagnetic Fields and Oxidative Stress—Biological Effects and Consequences for Health

“…The influence of electromagnetic fields (EMF), as a manmade environmental factor with increasing importance, on ROS formation, triggering oxidative stress, has been repeatedly discussed. Corresponding hypotheses and experimental findings have been summarized and discussed in previous reviews on this topic [ 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 ]. Although there is consistent evidence for EMF-induced ROS formation in experimental studies, a complete picture and a scientific consensus have not yet emerged with regard to epidemiological association and possible negative and long-term consequences for health.…”

Exposure to 50 Hz magnetic field at 100 µT exert no DNA damage in cardiomyocytes

“…This may be due to the various equipment used to generate MFs, exposure conditions, experimental protocols and biological materials adopted by different groups. In addition, ELF-MF was suspected to perturb redox-responsive intracellular signaling (Falone et al, 2018), while different cell types with specific redox status might have different cellular responses to ELF-MFs (Simko, 2007). Therefore, the effects of ELF-MFs on DNA damage still require further investigation.…”