Analysis of DNA Double-Strand Breaks and Cytotoxicity after 7 Tesla Magnetic Resonance Imaging of Isolated Human Lymphocytes

Abstract

The global use of magnetic resonance imaging (MRI) is constantly growing and the field strengths increasing. Yet, only little data about harmful biological effects caused by MRI exposure are available and published research analyzing the impact of MRI on DNA integrity reported controversial results. This in vitro study aimed to investigate the genotoxic and cytotoxic potential of 7 T ultra-high-field MRI on isolated human peripheral blood mononuclear cells. Hence, unstimulated mononuclear blood cells were exposed to 7 T static magnetic field alone or in combination with maximum permissible imaging gradients and radiofrequency pulses as well as to ionizing radiation during computed tomography and γ-ray exposure. DNA double-strand breaks were quantified by flow cytometry and automated microscopy analysis of immunofluorescence stained γH2AX. Cytotoxicity was studied by CellTiter-Blue viability assay and [3H]-thymidine proliferation assay. Exposure of unstimulated mononuclear blood cells to 7 T static magnetic field alone or combined with varying gradient magnetic fields and pulsed radiofrequency fields did not induce DNA double-strand breaks, whereas irradiation with X- and γ-rays led to a dose-dependent induction of γH2AX foci. The viability assay revealed a time- and dose-dependent decrease in metabolic activity only among samples exposed to γ-radiation. Further, there was no evidence for altered proliferation response after cells were exposed to 7 T MRI or low doses of ionizing radiation (≤ 0.2 Gy). These findings confirm the acceptance of MRI as a safe non-invasive diagnostic imaging tool, but whether MRI can induce other types of DNA lesions or DNA double-strand breaks during altered conditions still needs to be investigated.

Comments on potential health effects of MRI-induced DNA lesions: quality is more important to consider than quantity

“…Three of the studies showed no enhancement of DSB following either in vitro exposure of human cancer cell lines 0, 1, or 24 h post exposure, 18 in vitro exposure of human lymphocytes 0, 1, or 20 h post exposure, 23 or in human lymphocytes taken 5 min after in vivo exposure of patients undergoing contrast-enhanced cardiac magnetic resonance imaging (CMR). 22 In contrast, Fiechter et al 8 reported a statistically significant enhancement in DSB in human lymphocytes taken from patients immediately following contrast-enhanced CMR.…”

Mobile phone radiofrequency exposure has no effect on DNA double strand breaks (DSB) in human lymphocytes

“…The platform, named AKLIDES (Medipan, Dahlewitz, Germany), permits a fully automated assessment of antinuclear immunofluorescence antibody screening (12), but also allows computational analysis of γ-H2AX foci, which has now been successfully validated by several independent research groups (13)(14)(15)(16)(17). The suitability of the γH2AX assay to evaluate the dose-dependent formation of DSB has also been recently demonstrated for X-ray radiation and 7 Tesla magnetic resonance image exposure (17)(18)(19)(20). Therefore, the aim of the present study was to investigate the potential genotoxic effect of mobile phone RF exposure on human peripheral blood mononuclear cells (PBMCs) in vitro.…”

Valid Exposure Protocols Needed in Magnetic Resonance Imaging Genotoxic Research

“…In the other studies, various combinations of clinical MRI sequences were used. In some cases, the sequences were only mentioned by name [Simi et al, 2008;Lee et al, 2011;Szerencsi et al, 2013;Critchley et al, 2018], and in other cases, they were described with more details about the specific settings used [Schwenzer et al, 2007a,b;Reddig et al, 2015;Fatahi et al, 2016;Friebe et al, 2018].…”

“…Four studies gave no specifics about the gradient fields involved [Simi et al, 2008;Lee et al, 2011;Szerencsi et al, 2013;Critchley et al, 2018], making the exposure conditions impossible to replicate. The remaining four studies [Schwenzer et al, 2007a,b;Reddig et al, 2015;Fatahi et al, 2016;Friebe et al, 2018] provided peak gradient field strengths and peak slew rates, which could be useful information together with the exact position of the sample. Unfortunately, the position of the sample was either not given [Schwenzer et al, 2007a] or not specific [Reddig et al, 2015;Fatahi et al, 2016;Friebe et al, 2018].…”

“…The remaining four studies [Schwenzer et al, 2007a,b;Reddig et al, 2015;Fatahi et al, 2016;Friebe et al, 2018] provided peak gradient field strengths and peak slew rates, which could be useful information together with the exact position of the sample. Unfortunately, the position of the sample was either not given [Schwenzer et al, 2007a] or not specific [Reddig et al, 2015;Fatahi et al, 2016;Friebe et al, 2018]. Fatahi et al [2016] placed samples in "close proximity (2-7 cm) to the isocenter."…”