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

Huang CY, Chang CW, Chen CR, Chuang CY, Chiang CS, Shu WY, Fan TC, Hsu IC - PLoS ONE (2014)

Bottom Line: The ELF-EMF could cause G1 arrest and decrease colony formation.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.These findings indicate that ELF-EMFs activate the ATM-Chk2-p21 pathway in HaCaT cells, resulting in cell cycle arrest at the G1 phase.

View Article: PubMed Central - PubMed

Affiliation: Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University, 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.

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Related in: MedlinePlus

Cell cycle distribution in the sham (S) and exposed (E) HaCaT cells under ELF-EMF exposure.HaCaT cells were exposed to ELF-EMF for 48 to 144 h and analyzed by PI staining and flow cytometry. The percentage of the cell cycle growth phases were represented as the mean ± SD of three independent experiments. The Student’s t-test was used to analyze the differences between the sham and exposure groups. *P<0.05.
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pone-0104732-g002: Cell cycle distribution in the sham (S) and exposed (E) HaCaT cells under ELF-EMF exposure.HaCaT cells were exposed to ELF-EMF for 48 to 144 h and analyzed by PI staining and flow cytometry. The percentage of the cell cycle growth phases were represented as the mean ± SD of three independent experiments. The Student’s t-test was used to analyze the differences between the sham and exposure groups. *P<0.05.

Mentions: To investigate whether ELF-EMFs disturbed cell cycle progression, the cell cycle distribution between 48 and 144 h of ELF-EMF exposure was analyzed by propidium iodide (PI) staining and flow cytometry. As shown in Figure 2, at the 144-h time point, the percentage of exposed cells in the G0/G1 phase (78.82%±1.57%) was higher than that in the sham-exposed cells (56.02%±0.94%). No significant difference in the sub-G0/G1 phase of cell fractions was observed between the sham and exposed cells. This demonstrated that the G1-phase cell cycle arrest was induced after 144 h of ELF-EMF exposure.


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

Huang CY, Chang CW, Chen CR, Chuang CY, Chiang CS, Shu WY, Fan TC, Hsu IC - PLoS ONE (2014)

Cell cycle distribution in the sham (S) and exposed (E) HaCaT cells under ELF-EMF exposure.HaCaT cells were exposed to ELF-EMF for 48 to 144 h and analyzed by PI staining and flow cytometry. The percentage of the cell cycle growth phases were represented as the mean ± SD of three independent experiments. The Student’s t-test was used to analyze the differences between the sham and exposure groups. *P<0.05.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4128733&req=5

pone-0104732-g002: Cell cycle distribution in the sham (S) and exposed (E) HaCaT cells under ELF-EMF exposure.HaCaT cells were exposed to ELF-EMF for 48 to 144 h and analyzed by PI staining and flow cytometry. The percentage of the cell cycle growth phases were represented as the mean ± SD of three independent experiments. The Student’s t-test was used to analyze the differences between the sham and exposure groups. *P<0.05.
Mentions: To investigate whether ELF-EMFs disturbed cell cycle progression, the cell cycle distribution between 48 and 144 h of ELF-EMF exposure was analyzed by propidium iodide (PI) staining and flow cytometry. As shown in Figure 2, at the 144-h time point, the percentage of exposed cells in the G0/G1 phase (78.82%±1.57%) was higher than that in the sham-exposed cells (56.02%±0.94%). No significant difference in the sub-G0/G1 phase of cell fractions was observed between the sham and exposed cells. This demonstrated that the G1-phase cell cycle arrest was induced after 144 h of ELF-EMF exposure.

Bottom Line: The ELF-EMF could cause G1 arrest and decrease colony formation.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.These findings indicate that ELF-EMFs activate the ATM-Chk2-p21 pathway in HaCaT cells, resulting in cell cycle arrest at the G1 phase.

View Article: PubMed Central - PubMed

Affiliation: Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University, 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.

Show MeSH
Related in: MedlinePlus