Evaluation of DNA Methylation Profiles of LINE-1, Alu and Ribosomal DNA Repeats in Human Cell Lines Exposed to Radiofrequency Radiation

2023 · Mixed · Low evidence

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MixedLow evidencePaper 446

In cervical cancer and neuroblastoma cell lines exposed to 900 MHz GSM-modulated RF-EMF, exposure did not affect DNAm of Alu elements in any cell line. RF-EMF exposure influenced DNAm of LINE-1 and ribosomal repeats, affecting average methylation profiles and…

Study snapshot

Publicationmanual · 2023
Study typein_vitro
Reported directionMixed
Evidence ratingLow

Abstract

Evaluation of DNA Methylation Profiles of LINE-1, Alu and Ribosomal DNA Repeats in Human Cell Lines Exposed to Radiofrequency Radiation Ravaioli F, Bacalini MG, Giuliani C, Pellegrini C, D'Silva C, De Fanti S, Pirazzini C, Giorgi G, Del Re B. Evaluation of DNA Methylation Profiles of LINE-1, Alu and Ribosomal DNA Repeats in Human Cell Lines Exposed to Radiofrequency Radiation. Int J Mol Sci. 2023 May 27;24(11):9380. doi: 10.3390/ijms24119380. Abstract A large body of evidence indicates that environmental agents can induce alterations in DNA methylation (DNAm) profiles. Radiofrequency electromagnetic fields (RF-EMFs) are radiations emitted by everyday devices, which have been classified as "possibly carcinogenic"; however, their biological effects are unclear. As aberrant DNAm of genomic repetitive elements (REs) may promote genomic instability, here, we sought to determine whether exposure to RF-EMFs could affect DNAm of different classes of REs, such as long interspersed nuclear elements- 1 (LINE-1), Alu short interspersed nuclear elements and ribosomal repeats. To this purpose, we analysed DNAm profiles of cervical cancer and neuroblastoma cell lines (HeLa, BE(2)C and SH-SY5Y) exposed to 900 MHz GSM- modulated RF-EMF through an Illumina-based targeted deep bisulfite sequencing approach. Our findings showed that radiofrequency exposure did not affect the DNAm of Alu elements in any of the cell lines analysed. Conversely, it influenced DNAm of LINE-1 and ribosomal repeats in terms of both average profiles and organisation of methylated and unmethylated CpG sites, in different ways in each of the three cell lines studied. Excerpt The issue of what molecular mechanisms underlie the biological effects of EMFs on DNAm regulation is still an open question [58,59,60]. One intriguing hypothesis is that the biological effects of EMFs are mediated by free radicals. Emerging evidence suggests EMFs can induce changes in the energy levels of certain molecules, affecting the concentration of free radicals such as reactive oxygen species (ROS) [44,61,62,63,64,65,66,67,68]. In turn, ROS can affect both genome-wide and site-specific DNAm patterns [69,70,71,72,73]. In this study, this possible biological mechanism of RF-EMF was not evaluated in depth, as ROS levels were not measured, nor were ROS-exposed controls included. Future studies will be needed to determine whether ROS production may play a role in the alterations of DNAm of RE in the context of radiofrequency radiation exposure. Moreover, our results indicate that the effect on DNAm of LINE-1 and rDNA strongly depends on the cellular system considered and on the genetic background, in agreement with the fact that epigenetic modifications are tissue-specific and show inter-individual variability. Previous studies showed that the biological model is relevant in EMF exposure studies. For example, Martin et al. [74] studied the expression of three genes in three primary cultures of human keratinocytes subjected to identical exposure conditions (60.4 GHz) and found 3 different expression profiles. They speculated that this fact could be due to epigenetic modifications specific to each cellular model used. Similar results were found by Del Re et al. [43] studying the expression of some repetitive elements in HeLa, Be(2)C and SH-SY5Y cell lines. Collectively, these data indicate that many different models should be studied to understand the epigenetic effects of EMF exposure on biological samples. In conclusion, our results suggest that RF-EMF exposure can affect the DNAm of LINE-1 and rDNA sequences, which are highly represented in the human genome, and that the effects depend on cell context (cell genome and cell type). Further investigations on the epigenetic effects of RF-EMF would be useful both for a better understanding of RF-EMF risks and safety assessment. Open access paper: mdpi.com

Machine Enhanced Logic

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 directionmixed
PopulationHuman cell lines (HeLa cervical cancer; BE(2)C and SH-SY5Y neuroblastoma)
Sample sizeNot supplied
ExposureRF · 900 MHz
Evidence strengthLowConfidence: 74% · Peer reviewed: yes

Main findings

In cervical cancer and neuroblastoma cell lines exposed to 900 MHz GSM-modulated RF-EMF, exposure did not affect DNAm of Alu elements in any cell line. RF-EMF exposure influenced DNAm of LINE-1 and ribosomal repeats, affecting average methylation profiles and the organization of methylated/unmethylated CpG sites, with effects differing across the three cell lines.

Outcomes measured

  • DNA methylation (DNAm) profiles of repetitive elements: LINE-1
  • DNA methylation (DNAm) profiles of repetitive elements: Alu
  • DNA methylation (DNAm) profiles of ribosomal DNA (rDNA) repeats
  • Organization/patterning of methylated vs unmethylated CpG sites within repeats

Limitations

  • Reactive oxygen species (ROS) levels were not measured and ROS-exposed controls were not included, so a proposed ROS-mediated mechanism was not evaluated in depth.
  • Effects on DNAm of LINE-1 and rDNA depended on the cellular system/genetic background, limiting generalization across models.
  • Sample size and exposure duration/SAR were not stated in the provided abstract/metadata.
View raw extracted JSON
{
  "study_type": "in_vitro",
  "exposure": {
    "band": "RF",
    "source": null,
    "frequency_mhz": 900,
    "sar_wkg": null,
    "duration": null
  },
  "population": "Human cell lines (HeLa cervical cancer; BE(2)C and SH-SY5Y neuroblastoma)",
  "sample_size": null,
  "outcomes": [
    "DNA methylation (DNAm) profiles of repetitive elements: LINE-1",
    "DNA methylation (DNAm) profiles of repetitive elements: Alu",
    "DNA methylation (DNAm) profiles of ribosomal DNA (rDNA) repeats",
    "Organization/patterning of methylated vs unmethylated CpG sites within repeats"
  ],
  "main_findings": "In cervical cancer and neuroblastoma cell lines exposed to 900 MHz GSM-modulated RF-EMF, exposure did not affect DNAm of Alu elements in any cell line. RF-EMF exposure influenced DNAm of LINE-1 and ribosomal repeats, affecting average methylation profiles and the organization of methylated/unmethylated CpG sites, with effects differing across the three cell lines.",
  "effect_direction": "mixed",
  "limitations": [
    "Reactive oxygen species (ROS) levels were not measured and ROS-exposed controls were not included, so a proposed ROS-mediated mechanism was not evaluated in depth.",
    "Effects on DNAm of LINE-1 and rDNA depended on the cellular system/genetic background, limiting generalization across models.",
    "Sample size and exposure duration/SAR were not stated in the provided abstract/metadata."
  ],
  "evidence_strength": "low",
  "confidence": 0.74,
  "peer_reviewed_likely": "yes",
  "keywords": [
    "radiofrequency electromagnetic fields",
    "RF-EMF",
    "900 MHz",
    "GSM-modulated",
    "DNA methylation",
    "epigenetics",
    "repetitive elements",
    "LINE-1",
    "Alu",
    "ribosomal DNA",
    "rDNA",
    "HeLa",
    "BE(2)C",
    "SH-SY5Y",
    "Illumina targeted deep bisulfite sequencing"
  ],
  "suggested_hubs": [
    {
      "slug": "who-icnirp",
      "weight": 0.2,
      "reason": "Mentions RF-EMFs classified as 'possibly carcinogenic' and discusses safety/risk context, but no specific WHO/ICNIRP policy content in abstract."
    }
  ]
}
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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: 10.3390/ijms24119380
PubMed: Not supplied

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