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

PloS one · 2014 · Harm · Low evidence

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HarmLow evidencePaper 4675

Human HaCaT cells exposed to a 1.5 mT, 60 Hz ELF-EMF for 144 h showed G1 phase arrest, decreased colony formation, and activation of the ATM/Chk2 signaling cascade with increased p21 protein expression versus sham exposure. Suppression of CHK2 by siRNA dimini…

Study snapshot

PublicationPloS one · 2014
Study typein_vitro
Reported directionHarm
Evidence ratingLow

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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AI evidence extraction

Structured fields below were generated from the paper’s abstract and metadata to make the evidence easier to inspect. Automated extraction may be incomplete or incorrect; verify important details against the original paper.

Study typein_vitro
Effect directionharm
PopulationHuman HaCaT cells (immortalized epidermal keratinocyte cell line)
Sample sizeNot supplied
ExposureELF · 6e-05 MHz · 144 h
Evidence strengthLowConfidence: 74% · Peer reviewed: yes

Main findings

Human HaCaT cells exposed to a 1.5 mT, 60 Hz ELF-EMF for 144 h showed G1 phase arrest, decreased colony formation, and activation of the ATM/Chk2 signaling cascade with increased p21 protein expression versus sham exposure. Suppression of CHK2 by siRNA diminished the ELF-EMF-induced G1 arrest.

Outcomes measured

  • ATM-Chk2-p21 pathway activation
  • Cell proliferation
  • G1 phase cell cycle arrest
  • Colony formation
  • ATM/Chk2 signaling activation
  • p21 protein expression
  • Effect of CHK2 suppression (siRNA) on G1 arrest

Limitations

  • Sample size not reported in abstract.
  • In vitro cell-line study; findings may not generalize to humans or in vivo conditions.
  • Exposure described as 60 Hz, 1.5 mT for 144 h; other exposure conditions not assessed in abstract.
View raw extracted JSON
{
  "study_type": "in_vitro",
  "exposure": {
    "band": "ELF",
    "source": "electric appliances",
    "frequency_mhz": 6e-05,
    "sar_wkg": null,
    "duration": "144 h"
  },
  "population": "Human HaCaT cells (immortalized epidermal keratinocyte cell line)",
  "sample_size": null,
  "outcomes": [
    "ATM-Chk2-p21 pathway activation",
    "Cell proliferation",
    "G1 phase cell cycle arrest",
    "Colony formation",
    "ATM/Chk2 signaling activation",
    "p21 protein expression",
    "Effect of CHK2 suppression (siRNA) on G1 arrest"
  ],
  "main_findings": "Human HaCaT cells exposed to a 1.5 mT, 60 Hz ELF-EMF for 144 h showed G1 phase arrest, decreased colony formation, and activation of the ATM/Chk2 signaling cascade with increased p21 protein expression versus sham exposure. Suppression of CHK2 by siRNA diminished the ELF-EMF-induced G1 arrest.",
  "effect_direction": "harm",
  "limitations": [
    "Sample size not reported in abstract.",
    "In vitro cell-line study; findings may not generalize to humans or in vivo conditions.",
    "Exposure described as 60 Hz, 1.5 mT for 144 h; other exposure conditions not assessed in abstract."
  ],
  "evidence_strength": "low",
  "confidence": 0.74,
  "peer_reviewed_likely": "yes",
  "keywords": [
    "ELF-EMF",
    "extremely low-frequency electromagnetic fields",
    "60 Hz",
    "1.5 mT",
    "HaCaT",
    "keratinocyte",
    "ATM",
    "Chk2",
    "p21",
    "cell cycle",
    "G1 arrest",
    "colony formation",
    "siRNA"
  ],
  "suggested_hubs": [
    {
      "slug": "elf-emf",
      "weight": 0.9,
      "reason": "Study examines biological effects of extremely low-frequency (60 Hz) magnetic field exposure."
    }
  ]
}
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AI-extracted fields are generated from the abstract and metadata and may be incomplete or incorrect. This material is for informational purposes and is not medical advice.

Identifiers and source

DOI: 10.1371/journal.pone.0104732
PubMed: 25111195

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