Extremely Low-Frequency Electromagnetic Fields Cause G1 Phase Arrest through the Activation of the ATM-Chk2-p21 Pathway

Abstract

In daily life, humans are exposed to the extremely low-frequency electromagnetic fields (ELF-EMFs) generated by electric appliances, and public concern is increasing regarding the biological effects of such exposure. Numerous studies have yielded inconsistent results regarding the biological effects of ELF-EMF exposure. Here we show that ELF-EMFs activate the ATM-Chk2-p21 pathway in HaCaT cells, inhibiting cell proliferation. To present well-founded results, we comprehensively evaluated the biological effects of ELF-EMFs at the transcriptional, protein, and cellular levels. Human HaCaT cells from an immortalized epidermal keratinocyte cell line were exposed to a 1.5 mT, 60 Hz ELF-EMF for 144 h. The ELF-EMF could cause G1 arrest and decrease colony formation. Protein expression experiments revealed that ELF-EMFs induced the activation of the ATM/Chk2 signaling cascades. In addition, the p21 protein, a regulator of cell cycle progression at G1 and G2/M, exhibited a higher level of expression in exposed HaCaT cells compared with the expression of sham-exposed cells. The ELF-EMF-induced G1 arrest was diminished when the CHK2 gene expression (which encodes checkpoint kinase 2; Chk2) was suppressed by specific small interfering RNA (siRNA). These findings indicate that ELF-EMFs activate the ATM-Chk2-p21 pathway in HaCaT cells, resulting in cell cycle arrest at the G1 phase. Based on the precise control of the ELF-EMF exposure and rigorous sham-exposure experiments, all transcriptional, protein, and cellular level experiments consistently supported the conclusion. This is the first study to confirm that a specific pathway is triggered by ELF-EMF exposure.

The antitumor effect of static and extremely low frequency magnetic fields against nephroblastoma and neuroblastoma

“…Under the current exposure protocol, the modulated MF interferes with cell proliferation and could induce apoptosis. This is in accordance with several previous reports about MF-induced cell cycle arrest [Wang et al, 2011;Huang et al, 2014;Jin et al, 2015], which can subsequently activate the apoptosis pathway. Moreover, the change of cell proliferation and apoptosis was more significant on day 2 compared with day 3, suggesting the cells may develop a resistance mechanism during persisted MF exposure.…”

Activation of Signaling Cascades by Weak Extremely Low Frequency Electromagnetic Fields

“…Another important signaling mechanism that appears to be influenced by ELF-MF is the elevation of intracellular Ca 2+ in exposed cells [24,25] within 1 min of exposure to ELF-MF at 50 Hz and 0.1 mT. Interestingly, the calcium response, as well as other signaling processes, is elevated upon long-term (> 3 h) ELF-MF exposure as well [26][27][28], but these effects are due to downstream processes rather than to a direct effect of the radiation [29].…”

Effects of extremely low frequency electromagnetic field (ELF-EMF) on catalase, cytochrome P450 and nitric oxide synthase in erythro-leukemic cells

“…It can initiate a number of biochemical and physiological alterations in biological systems of different species [18,21,40]. The biological effects in cell lines exposed to ELF-EMFs have been frequently noted [19,24,35,33,42]. However, despite the large number of studies, an understanding is still lacking [12,25,46].…”