The Use of Signal-Transduction and Metabolic Pathways to Predict Human Disease Targets from Electric and Magnetic Fields Using in vitro Data in Human Cell Lines.

Meike Mevissen,Christopher J. Portier,Xiaoqing Chang,Fred Parham

doi:10.3389/fpubh.2016.00193

Abstract

Using in vitro data in human cell lines, several research groups have investigated changes in gene expression in cellular systems following exposure to extremely low frequency (ELF) and radiofrequency (RF) electromagnetic fields (EMF). For ELF EMF, we obtained five studies with complete microarray data and three studies with only lists of significantly altered genes. Likewise, for RF EMF, we obtained 13 complete microarray datasets and 5 limited datasets. Plausible linkages between exposure to ELF and RF EMF and human diseases were identified using a three-step process: (a) linking genes associated with classes of human diseases to molecular pathways, (b) linking pathways to ELF and RF EMF microarray data, and (c) identifying associations between human disease and EMF exposures where the pathways are significantly similar. A total of 60 pathways were associated with human diseases, mostly focused on basic cellular functions like JAK–STAT signaling or metabolic functions like xenobiotic metabolism by cytochrome P450 enzymes. ELF EMF datasets were sporadically linked to human diseases, but no clear pattern emerged. Individual datasets showed some linkage to cancer, chemical dependency, metabolic disorders, and neurological disorders. RF EMF datasets were not strongly linked to any disorders but strongly linked to changes in several pathways. Based on these analyses, the most promising area for further research would be to focus on EMF and neurological function and disorders.

Highlights

The worldwide use of mobile phones has aroused concern about possible health effects of radiofrequency electromagnetic fields (100 kHz–300 GHz; RF EMF) [1, 2]
Many studies have been performed on identifying genes being involved in biological effects caused by extremely low frequency (ELF) and RF EMF using a variety of mammalian cell lines and primary cells
The linkage was done in three steps: [1] linkage of human disease categories to KEGG pathways using genetic polymorphisms, [2] linkage of EMF exposure with KEGG pathways using gene array data, and [3] comparison of the disease-linked pathways with EMF-linked pathways to predict significant linkages between EMF and human disease

Summary

Introduction

The worldwide use of mobile phones has aroused concern about possible health effects of radiofrequency electromagnetic fields (100 kHz–300 GHz; RF EMF) [1, 2]. Many studies have been performed on identifying genes being involved in biological effects caused by ELF and RF EMF using a variety of mammalian cell lines and primary cells Most of these studies were hypothesis-driven and demonstrated changes in the expression of a limited number of genes, especially those involved in stress response [5,6,7,8,9,10,11,12,13,14,15,16,17,18], and cell cycle regulation and apoptosis [19,20,21,22,23], suggesting an upregulation or downregulation of the genes involved. The extracellular signal-regulated kinases (ERK) 1 and 2 are MAPKs that are important in cellular proliferation, differentiation, and survival

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Discussion

Conclusion