Static magnetic fields modulate X-ray-induced DNA damage in human glioblastoma primary cells

Abstract

Although static magnetic fields (SMFs) are used extensively in the occupational and medical fields, few comprehensive studies have investigated their possible genotoxic effect and the findings are controversial. With the advent of magnetic resonance imaging-guided radiation therapy, the potential effects of SMFs on ionizing radiation (IR) have become increasingly important. In this study we focused on the genotoxic effect of 80 mT SMFs, both alone and in combination with (i.e. preceding or following) X-ray (XR) irradiation, on primary glioblastoma cells in culture. The cells were exposed to: (i) SMFs alone; (ii) XRs alone; (iii) XR, with SMFs applied during recovery; (iv) SMFs both before and after XR irradiation. XR-induced DNA damage was analyzed by Single Cell Gel Electrophoresis assay (comet assay) using statistical tools designed to assess the tail DNA (TD) and tail length (TL) as indicators of DNA fragmentation. Mitochondrial membrane potential, known to be affected by IR, was assessed using the JC-1 mitochondrial probe. Our results showed that exposure of cells to 5 Gy of XR irradiation alone led to extensive DNA damage, which was significantly reduced by post-irradiation exposure to SMFs. The XR-induced loss of mitochondrial membrane potential was to a large extent averted by exposure to SMFs. These data suggest that SMFs modulate DNA damage and/or damage repair, possibly through a mechanism that affects mitochondria.

Biological effects of static magnetic field exposure in the context of MR-guided radiotherapy

“…62 In the last 5 years, three studies have been published on the topic of combined SMF and ionising radiation exposure in human cancer in vitro models. [63][64][65] Viability of lung adrenocarcinoma cells (cell line A549) treated with 0.5 T SMF alone for 1 to 4 h was significantly inhibited by approximately 10% relative to untreated cells (p < 0.05). 63 Gene chip analysis revealed that SMF exposure of 1 h produced alterations in gene expression associated with the promotion of cell cycle arrest and apoptosis.…”

“…the survival fraction at 10 Gy was 0.24 for B = 0 T and 0.02 for B = 0.5 T. Flow cytometry analysis linked SMF exposure with an increase in the proportion of cells in phase G2 and M, the most radiosensitive phases, suggesting that SMF may act to radiosensitize A549 cells by influencing cell cycle progression via an unidentified interaction mechanism. 63 Teodori et al 64 studied the impact of 0.08 T SMF in combination with orthovoltage X-ray irradiation on DNA damage (comet assay) and mitochondrial membrane potential (JC-1 probe) in human primary glioblastoma cells in vitro. SMF exposure (24 h) without irradiation was associated with a significant increase in DNA damage (p < 0.01), 64 which concords with the SMF-related viability reduction observed by Feng et al 63 Intriguingly, glioblastoma DNA damage was significantly reduced by 6 and 20 h SMF exposure post-irradiation (p < 0.001), while the inclusion of an additional 6 h SMF pre-treatment did not impact this result.…”

“…63 Teodori et al 64 studied the impact of 0.08 T SMF in combination with orthovoltage X-ray irradiation on DNA damage (comet assay) and mitochondrial membrane potential (JC-1 probe) in human primary glioblastoma cells in vitro. SMF exposure (24 h) without irradiation was associated with a significant increase in DNA damage (p < 0.01), 64 which concords with the SMF-related viability reduction observed by Feng et al 63 Intriguingly, glioblastoma DNA damage was significantly reduced by 6 and 20 h SMF exposure post-irradiation (p < 0.001), while the inclusion of an additional 6 h SMF pre-treatment did not impact this result. 64 X-ray induced loss of mitochondrial membrane potential was diminished by exposure to SMFs during recovery, suggesting a potential link between the protection of mitochondria by SMF (possibly via SMF perturbation of the electron transport chain in mitochondria) and a reduction in radiation-induced genotoxicity.…”

“…64 X-ray induced loss of mitochondrial membrane potential was diminished by exposure to SMFs during recovery, suggesting a potential link between the protection of mitochondria by SMF (possibly via SMF perturbation of the electron transport chain in mitochondria) and a reduction in radiation-induced genotoxicity. 64 The only study to have featured an MR-Linac (1.5 T SMF, 6 MV X-rays) was performed by Wang et al 65 Two human head and neck cancer and two lung cancer cell lines were studied in vitro. Robust dosimetry and the use of a cell irradiation jig to ensure high dose uniformity to the cells in the presence of SMF were strengths of this work.…”

Static Magnetic Fields Modulate the Response of Different Oxidative Stress Markers in a Restraint Stress Model Animal

“…These studies demonstrated that exposure to SMF could have both beneficial and detrimental biological consequences. For example, SMF exposure increases the total antioxidant capacity, decreases allergic inflammation [ 22 ], enriches trace elements [ 23 ], and modulates DNA damage and/or damage repair, possibly through mitochondrial mechanisms [ 24 , 25 ]. SMFs could also inhibit the proliferation of some human cells [ 26 ], increase apoptosis and necrosis via changes in the cell viability and lipid peroxidation [ 27 ], and stimulate lipid peroxidation in the liver [ 28 ].…”