Extremely low-frequency electromagnetic fields cause G1 phase arrest through the activation of the ATM-Chk2-p21 pathway

Chao-Ying Huang; Cheng-Wei Chang; Chaang-Ray Chen; Chun-Yu Chuang; Chi-Shiun Chiang; Wun-Yi Shu; Tai-Ching Fan; Ian C Hsu

doi:10.1371/journal.pone.0104732

Extremely low-frequency electromagnetic fields cause G1 phase arrest through the activation of the ATM-Chk2-p21 pathway

PLoS One. 2014 Aug 11;9(8):e104732. doi: 10.1371/journal.pone.0104732. eCollection 2014.

Authors

Chao-Ying Huang¹, Cheng-Wei Chang¹, Chaang-Ray Chen¹, Chun-Yu Chuang¹, Chi-Shiun Chiang¹, Wun-Yi Shu², Tai-Ching Fan³, Ian C Hsu¹

Affiliations

¹ Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University, Hsinchu, Taiwan.
² Institute of Statistics, National Tsing Hua University, Hsinchu, Taiwan.
³ Magnet Group, Instrumentation Development Division, National Synchrotron Radiation Research Center, Hsinchu, Taiwan.

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Ataxia Telangiectasia Mutated Proteins / metabolism*
Cell Line
Cell Proliferation / radiation effects
Checkpoint Kinase 2 / metabolism*
Cyclin-Dependent Kinase Inhibitor p21 / metabolism*
Electromagnetic Fields / adverse effects*
G1 Phase Cell Cycle Checkpoints / radiation effects*
Humans
Signal Transduction / radiation effects*
Transcriptome / radiation effects

Substances

Cyclin-Dependent Kinase Inhibitor p21
Checkpoint Kinase 2
Ataxia Telangiectasia Mutated Proteins

Grants and funding

The authors would like to thank the National Science Council, Taiwan, for supporting this research financially under Contract (Grant number: NSC 101-2112 M-007-003-MY3, http://web1.most.gov.tw/). The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.