title: 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.
authors.affiliation: Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University, Hsinchu, Taiwan.
authors.forename: Chao-Ying
authors.initials: CY
authors.lastname: Huang
authors.affiliation: Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University, Hsinchu, Taiwan.
authors.forename: Cheng-Wei
authors.initials: CW
authors.lastname: Chang
authors.affiliation: Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University, Hsinchu, Taiwan.
authors.forename: Chaang-Ray
authors.initials: CR
authors.lastname: Chen
authors.affiliation: Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University, Hsinchu, Taiwan.
authors.forename: Chun-Yu
authors.initials: CY
authors.lastname: Chuang
authors.affiliation: Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University, Hsinchu, Taiwan.
authors.forename: Chi-Shiun
authors.initials: CS
authors.lastname: Chiang
authors.affiliation: Institute of Statistics, National Tsing Hua University, Hsinchu, Taiwan.
authors.forename: Wun-Yi
authors.initials: WY
authors.lastname: Shu
authors.affiliation: Magnet Group, Instrumentation Development Division, National Synchrotron Radiation Research Center, Hsinchu, Taiwan.
authors.forename: Tai-Ching
authors.initials: TC
authors.lastname: Fan
authors.affiliation: Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University, Hsinchu, Taiwan.
authors.forename: Ian C
authors.initials: IC
authors.lastname: Hsu
mesh_terms: D064007:Ataxia Telangiectasia Mutated Proteins / Q000378:metabolism*; D002460:Cell Line; D049109:Cell Proliferation / Q000528:radiation effects; D064447:Checkpoint Kinase 2 / Q000378:metabolism*; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism*; D004574:Electromagnetic Fields / Q000009:adverse effects*; D059585:G1 Phase Cell Cycle Checkpoints / Q000528:radiation effects*; D006801:Humans; D015398:Signal Transduction / Q000528:radiation effects*; D059467:Transcriptome / Q000528:radiation effects
chemical_list: D050759:Cyclin-Dependent Kinase Inhibitor p21; D064447:Checkpoint Kinase 2; D064007:Ataxia Telangiectasia Mutated Proteins
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