Exposure to long-term evolution radiofrequency electromagnetic fields decreases neuroblastoma cell proliferation via Akt/mTOR-mediated cellular senescence.

Abstract

The aim of this study was to examine the potential effects of long-term evolution (LTE) radiofrequency electromagnetic fields (RF-EMF) on cell proliferation using SH-SY5Y neuronal cells. The growth rate and proliferation of SH-SY5Y cells were significantly decreased upon exposure to 1760 MHz RF-EMF at 4 W/kg specific absorption rate (SAR) for 4 hr/day for 4 days. Cell cycle analysis indicated that the cell cycle was delayed in the G0/G1 phase after RF-EMF exposure. However, DNA damage or apoptosis was not involved in the reduced cellular proliferation following RF-EMF exposure because the expression levels of histone H2A.X at Ser139 (γH2AX) were not markedly altered and the apoptotic pathway was not activated. However, SH-SY5Y cells exposed to RF-EMF exhibited a significant elevation in Akt and mTOR phosphorylation levels. In addition, the total amount of p53 and phosphorylated-p53 was significantly increased. Data suggested that Akt/mTOR-mediated cellular senescence led to p53 activation via stimulation of the mTOR pathway in SH-SY5Y cells. The transcriptional activation of p53 led to a rise in expression of cyclin-dependent kinase (CDK) inhibitors p21 and p27. Further, subsequent inhibition of CDK2 and CDK4 produced a fall in phosphorylated retinoblastoma (pRb at Ser807/811), which decreased cell proliferation. Taken together, these data suggest that exposure to RF-EMF might induce Akt/mTOR-mediated cellular senescence, which may delay the cell cycle without triggering DNA damage in SH-SY5Y neuroblastoma cells.

AI evidence extraction

Main findings

Exposure to 1760 MHz LTE RF-EMF at 4 W/kg SAR for 4 hr/day for 4 days significantly decreased SH-SY5Y cell growth rate and proliferation and delayed the cell cycle in G0/G1. The authors report no marked change in γH2AX and no activation of apoptosis, while observing increased Akt/mTOR phosphorylation and increased p53 (total and phosphorylated) with downstream increases in p21/p27 and reduced pRb phosphorylation, consistent with Akt/mTOR-mediated cellular senescence.

Outcomes measured

• Cell growth rate
• Cell proliferation
• Cell cycle distribution (G0/G1 delay)
• DNA damage marker γH2AX (H2A.X Ser139)
• Apoptosis pathway activation
• Akt phosphorylation
• mTOR phosphorylation
• p53 total and phosphorylated p53
• p21 and p27 expression
• CDK2 and CDK4 inhibition
• pRb phosphorylation (Ser807/811)
• Cellular senescence (Akt/mTOR-mediated)

{
    "study_type": "in_vitro",
    "exposure": {
        "band": "RF",
        "source": "LTE",
        "frequency_mhz": 1760,
        "sar_wkg": 4,
        "duration": "4 hr/day for 4 days"
    },
    "population": "SH-SY5Y neuroblastoma (neuronal) cells",
    "sample_size": null,
    "outcomes": [
        "Cell growth rate",
        "Cell proliferation",
        "Cell cycle distribution (G0/G1 delay)",
        "DNA damage marker γH2AX (H2A.X Ser139)",
        "Apoptosis pathway activation",
        "Akt phosphorylation",
        "mTOR phosphorylation",
        "p53 total and phosphorylated p53",
        "p21 and p27 expression",
        "CDK2 and CDK4 inhibition",
        "pRb phosphorylation (Ser807/811)",
        "Cellular senescence (Akt/mTOR-mediated)"
    ],
    "main_findings": "Exposure to 1760 MHz LTE RF-EMF at 4 W/kg SAR for 4 hr/day for 4 days significantly decreased SH-SY5Y cell growth rate and proliferation and delayed the cell cycle in G0/G1. The authors report no marked change in γH2AX and no activation of apoptosis, while observing increased Akt/mTOR phosphorylation and increased p53 (total and phosphorylated) with downstream increases in p21/p27 and reduced pRb phosphorylation, consistent with Akt/mTOR-mediated cellular senescence.",
    "effect_direction": "harm",
    "limitations": [],
    "evidence_strength": "low",
    "confidence": 0.7399999999999999911182158029987476766109466552734375,
    "peer_reviewed_likely": "yes",
    "keywords": [
        "LTE",
        "RF-EMF",
        "1760 MHz",
        "specific absorption rate",
        "SAR 4 W/kg",
        "SH-SY5Y",
        "neuroblastoma",
        "cell proliferation",
        "cell cycle",
        "G0/G1",
        "Akt",
        "mTOR",
        "p53",
        "p21",
        "p27",
        "cellular senescence",
        "γH2AX",
        "apoptosis"
    ],
    "suggested_hubs": []
}

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