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.

AI evidence extraction

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.

Suggested hubs

• elf-emf (0.9)
  Study examines biological effects of extremely low-frequency (60 Hz) magnetic field exposure.

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    "study_type": "in_vitro",
    "exposure": {
        "band": "ELF",
        "source": "electric appliances",
        "frequency_mhz": 6.00000000000000015200514458246772164784488268196582794189453125e-5,
        "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": 0.7399999999999999911182158029987476766109466552734375,
    "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": [
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            "slug": "elf-emf",
            "weight": 0.90000000000000002220446049250313080847263336181640625,
            "reason": "Study examines biological effects of extremely low-frequency (60 Hz) magnetic field exposure."
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