A systematic review on cellular responses of Escherichia coli to nonthermal electromagnetic

Abstract

A systematic review on cellular responses of Escherichia coli to nonthermal electromagnetic irradiation Askaripour K, Żak A. A systematic review on cellular responses of Escherichia coli to nonthermal electromagnetic irradiation. Bioelectromagnetics. 2024 Jan;45(1):16-29. doi: 10.1002/bem.22484. Highlights • The present review aims to systematically evaluate literature to reach a firm conclusion on the causality between nonthermal electromagnetic radiation of alternating current and biological effects in Escherichia coli. • The systematic review methodology by OHAT and the risk of bias tool evaluating the validity of experimental design and conduct within research works were followed. • With 25 of the 114 records screened meeting the eligibility criteria, the evidence summation was performed regarding growth rate, morphology, and gene expression under exposure of extremely low frequency, intermediate frequency, or radio frequency. • With 85% of experiments in the included studies focusing on the extremely low-frequency range, effects on growth rate, morphology, and gene expression were supported in 74%, 80%, and 33% of the experiments, respectively. Abstract Investigation of Escherichia coli under electromagnetic fields is of significance in human studies owing to its short doubling time and human-like DNA mechanisms. The present review aims to systematically evaluate the literature to conclude causality between 0 and 300 GHz electromagnetic fields and biological effects in E. coli. To that end, the OHAT methodology and risk of bias tool were employed. Exponentially growing cells exposed for over 30 min at temperatures up to 37∘C with fluctuations below 1∘C were included from the Web-of-Knowledge, PubMed, or EMF-Portal databases. Out of 904 records identified, 25 articles satisfied the selection criteria, with four excluded during internal validation. These articles examined cell growth (11 studies), morphology (three studies), and gene regulation (11 studies). Most experiments (85%) in the included studies focused on the extremely low-frequency (ELF) range, with 60% specifically at 50 Hz. Changes in growth rate were observed in 74% of ELF experiments and 71% of radio frequency (RF) experiments. Additionally, 80% of ELF experiments showed morphology changes, while gene expression changes were seen in 33% (ELF) and 50% (RF) experiments. Due to the limited number of studies, especially in the intermediate frequency and RF ranges, establishing correlations between EMF exposure and biological effects on E. coli is not possible. pubmed.ncbi.nlm.nih.gov Conclusions The present review systemically evaluates whether the current literature, passing through the risk of bias tool, while fulfilling the selection criteria defined in the PECO statement, supports an association between nonthermal electromagnetic fields and alterations in the biological composition and functioning of E. coli strains. The findings from the 21 included studies are dependent on the specific endpoints assessed, which include cell growth, morphology, and gene expression. The conclusions are subject to certain limitations, as the review focuses on exponentially growing strains that were exposed to nonthermal EMFs of frequencies 0–300 GHz for a minimum duration of 30 min. In each study, it is possible that multiple experiments were conducted. Among these studies, 85% of experiments (16 articles) focused on the extremely low-frequency range, with 60% specifically examining 50 Hz. Additionally, 5% of experiments (one article) addressed the IF range, while 10% of experiments (four articles) addressed the RF range. In the investigation of nonthermal effects of extremely low-frequency electromagnetic fields (ELF-EMF), 74% of the experiments supported the effects on growth rate (investigated in nine articles), 80% supported the effects on morphology (investigated in three articles), and 33% supported the effects on gene expression (investigated in eight articles). Within the IF range, nonthermal effects on growth rate were observed in 100% of experiments (conducted in one article), but no experiments supported such effects on gene expression (investigated in one article). In the RF range, 71% of experiments supported nonthermal effects on growth rate (conducted in two articles), while 50% supported nonthermal effects on gene expression (conducted in two articles). Therefore, due to the limited number of studies available on the IF and RF ranges, the reliability of the results may primarily apply to ELF-EMF, particularly at 50 Hz. When experiments demonstrated biological effects, the observed pattern varied as either beneficial or detrimental, depending on the exposure conditions and experimental setup. For example, out of 38 experiments on growth rate, 12 showed beneficial effects while 16 showed detrimental effects. This controversy can be explained by the concept of the biological window, in which EMF may contribute to positive physiological processes. However, if the accumulated exposure exceeds the cell-specific energy limit, detrimental effects may prevail. Several sources exhibited inconsistencies when observing these effects. In terms of exposure parameters, continuity, referring to intermittent or continuous status, had a significant effect on the results, with pulsed signals showing a greater impact compared to sinusoidal signals. Extremely low frequencies and radio frequencies had a major impact on the investigated endpoints, while intermediate frequencies have received limited research attention. The intensity and duration of exposure influenced the absorbed energy levels, resulting in varying effects ranging from beneficial to neutral or detrimental. Modulation may introduce significant differences compared to unmodulated signals, depending on the modulation frequency. The optimal measurement time point depends on the specific endpoint and necessitates mechanistic understanding for accurate identification. Special attention is needed regarding sufficient and clear reports on the amount of electromagnetic irradiation absorbed by the strains, as it can make the quantitative comparison between studies possible, and discriminate between nondetrimental or detrimental effects. Besides, special attention to the background electromagnetic irradiation as a confounder and the measurement time point for allowing the outcome to develop is required. Deficiencies associated with the risk of bias including research personnel blinded to the study group, randomization of exposure, allocation concealment, attrition/exclusion bias, and their possible effect on the outcome should be considered. More mechanistic investigations regarding cellular processes and their related genes are demanded. Based on the limited number of studies encompassing three different frequency ranges and three different endpoints, the systematic review does not establish a conclusive correlation between nonthermal exposure to electromagnetic fields and cellular alterations in E. coli strains. However, future research could explore this correlation more specifically, considering the similarity of endpoints and levels of exposure between E. coli and humans. This exploration would help shed light on the potential implications of these effects on human health.

AI evidence extraction

Main findings

Using OHAT methodology and a risk-of-bias tool, 25 articles met eligibility criteria (with four excluded during internal validation; conclusions refer to 21 included studies). Most experiments focused on ELF (85%; 60% at 50 Hz). Reported changes were observed in growth rate (74% of ELF experiments; 71% of RF experiments), morphology (80% of ELF experiments), and gene expression (33% of ELF; 50% of RF), but the review concludes that due to limited studies—especially in IF and RF—establishing correlations between EMF exposure and biological effects in E. coli is not possible.

Outcomes measured

• cell growth/growth rate
• morphology
• gene regulation/gene expression

Limitations

• Limited number of studies overall, particularly in intermediate frequency and radiofrequency ranges
• Heterogeneity/variability in exposure conditions and experimental setup; effects could be beneficial or detrimental depending on conditions
• Inconsistencies across sources/experiments
• Need for clearer reporting/quantification of absorbed electromagnetic irradiation to enable quantitative comparisons
• Potential confounding by background electromagnetic irradiation
• Methodological/risk-of-bias concerns noted (e.g., blinding, randomization of exposure, allocation concealment, attrition/exclusion bias)
• Outcome measurement time point may affect whether effects are observed

{
    "study_type": "systematic_review",
    "exposure": {
        "band": "ELF/IF/RF (0–300 GHz)",
        "source": null,
        "frequency_mhz": null,
        "sar_wkg": null,
        "duration": "≥30 min"
    },
    "population": "Escherichia coli (exponentially growing cells/strains)",
    "sample_size": 25,
    "outcomes": [
        "cell growth/growth rate",
        "morphology",
        "gene regulation/gene expression"
    ],
    "main_findings": "Using OHAT methodology and a risk-of-bias tool, 25 articles met eligibility criteria (with four excluded during internal validation; conclusions refer to 21 included studies). Most experiments focused on ELF (85%; 60% at 50 Hz). Reported changes were observed in growth rate (74% of ELF experiments; 71% of RF experiments), morphology (80% of ELF experiments), and gene expression (33% of ELF; 50% of RF), but the review concludes that due to limited studies—especially in IF and RF—establishing correlations between EMF exposure and biological effects in E. coli is not possible.",
    "effect_direction": "mixed",
    "limitations": [
        "Limited number of studies overall, particularly in intermediate frequency and radiofrequency ranges",
        "Heterogeneity/variability in exposure conditions and experimental setup; effects could be beneficial or detrimental depending on conditions",
        "Inconsistencies across sources/experiments",
        "Need for clearer reporting/quantification of absorbed electromagnetic irradiation to enable quantitative comparisons",
        "Potential confounding by background electromagnetic irradiation",
        "Methodological/risk-of-bias concerns noted (e.g., blinding, randomization of exposure, allocation concealment, attrition/exclusion bias)",
        "Outcome measurement time point may affect whether effects are observed"
    ],
    "evidence_strength": "low",
    "confidence": 0.7800000000000000266453525910037569701671600341796875,
    "peer_reviewed_likely": "yes",
    "keywords": [
        "Escherichia coli",
        "nonthermal electromagnetic fields",
        "ELF",
        "intermediate frequency",
        "radiofrequency",
        "0–300 GHz",
        "50 Hz",
        "OHAT",
        "risk of bias",
        "growth rate",
        "morphology",
        "gene expression"
    ],
    "suggested_hubs": []
}

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