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      Impact of Inhomogeneous Static Magnetic Field (31.7–232.0 mT) Exposure on Human Neuroblastoma SH-SY5Y Cells during Cisplatin Administration

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          Abstract

          Beneficial or adverse effects of Static Magnetic Fields (SMFs) are a large concern for the scientific community. In particular, the effect of SMF exposure during anticancer therapies still needs to be fully elucidated. Here, we evaluate the effects of SMF at induction levels that cisPt-treated cancer patients experience during the imaging process conducted in Low field (200–500 mT), Open field (300–700 mT) and/or inhomogeneous High field (1.5–3 T) Magnetic Resonance Imaging (MRI) machines. Human adrenergic neuroblastoma SH-SY5Y cells treated with 0.1 µM cisPt ( i.e. the lowest concentration capable of inducing apoptosis) were exposed to SMF and their response was studied in vitro. Exposure of 0.1 µM cisPt-treated cells to SMF for 2 h decreased cell viability (30%) and caused overexpression of the apoptosis-related cleaved caspase-3 protein (46%). Furthermore, increase in ROS (Reactive Oxygen Species) production (23%) and reduction in the number of mitochondria vs controls were seen. The sole exposure of SMF for up to 24 h had no effect on cell viability but increased ROS production and modified cellular shape. On the other hand, the toxicity of cisPt was significantly prevented during 24 h exposure to SMF as shown by the levels of cell viability, cleaved caspase-3 and ROS production. In conclusion, due to the cytoprotective effect of 31.7–232.0 mT SMF on low- cisPt-concentration-treated SH-SY5Y cells, our data suggest that exposure to various sources of SMF in cancer patients under a cisPt regimen should be strictly controlled.

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          Membrane and morphological changes in apoptotic cells regulated by caspase-mediated activation of PAK2.

          Apoptosis of Jurkat T cells induced the caspase-mediated proteolytic cleavage of p21-activated kinase 2 (PAK2). Cleavage occurred between the amino-terminal regulatory domain and the carboxyl-terminal catalytic domain, which generated a constitutively active PAK2 fragment. Stable Jurkat cell lines that expressed a dominant-negative PAK mutant were resistant to the Fas-induced formation of apoptotic bodies, but had an enhanced externalization of phosphatidylserine at the cell surface. Thus, proteolytic activation of PAK2 represents a guanosine triphosphatase-independent mechanism of PAK regulation that allows PAK2 to regulate morphological changes that are seen in apoptotic cells.
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            Bioeffects of Static Magnetic Fields: Oxidative Stress, Genotoxic Effects, and Cancer Studies

            The interaction of static magnetic fields (SMFs) with living organisms is a rapidly growing field of investigation. The magnetic fields (MFs) effect observed with radical pair recombination is one of the well-known mechanisms by which MFs interact with biological systems. Exposure to SMF can increase the activity, concentration, and life time of paramagnetic free radicals, which might cause oxidative stress, genetic mutation, and/or apoptosis. Current evidence suggests that cell proliferation can be influenced by a treatment with both SMFs and anticancer drugs. It has been recently found that SMFs can enhance the anticancer effect of chemotherapeutic drugs; this may provide a new strategy for cancer therapy. This review focuses on our own data and other data from the literature of SMFs bioeffects. Three main areas of investigation have been covered: free radical generation and oxidative stress, apoptosis and genotoxicity, and cancer. After an introduction on SMF classification and medical applications, the basic phenomena to understand the bioeffects are described. The scientific literature is summarized, integrated, and critically analyzed with the help of authoritative reviews by recognized experts; international safety guidelines are also cited.
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              Cisplatin binding sites on human albumin.

              Reactions of cisplatin (cis-[PtCl2(NH3)2]) with albumin are thought to play an important role in the metabolism of this anticancer drug. They are investigated here via (i) labeling of cisplatin with 15N and use of two-dimensional 1H,15N NMR spectroscopy, (ii) comparison of natural human serum albumin with recombinant human albumin (higher homogeneity and SH content), (iii) chemical modification of Cys, Met, and His residues, (iv) reactions of bound platinum with thiourea, and (v) gel filtration chromatography. In contrast to previous reports, it is shown that the major sulfur-containing binding site involves Met and not Cys-34, and also a N ligand, in the form of an S,N macrochelate. Additional monofunctional adducts involving other Met residues and Cys-34 are also observed. During the later stages of reactions of cisplatin with albumin, release of NH3 occurs due to the strong trans influence of Met sulfur, which weakens the Pt-NH3 bonds, and protein cross-linking is observed. The consequences of these findings for the biological activity of cisplatin-albumin complexes are discussed.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, USA )
                1932-6203
                2014
                25 November 2014
                : 9
                : 11
                : e113530
                Affiliations
                [1 ]Department of Biological and Environmental Science and Technology (Di.S.Te.B.A.), University of Salento, 73100 Lecce, Italy
                [2 ]Laboratory of Membrane Biophysics and Macromolecules, Institute of Biochemistry and Biophysics, University of Tehran, 13145-1384 Tehran, Iran
                [3 ]Neuroscience Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, 76175-113 Kerman, Iran
                [4 ]Biomaterials Research Center (BRC), University of Tehran, 13145-1384 Tehran, Iran
                Medical University of South Carolina, United States of America
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Conceived and designed the experiments: LD CV MA. Performed the experiments: MA CV. Analyzed the data: CV. Contributed reagents/materials/analysis tools: LD. Wrote the paper: LD CV HM.

                Article
                PONE-D-14-13172
                10.1371/journal.pone.0113530
                4244110
                25423171
                2962cda9-341c-47df-9f15-fd7409edd035
                Copyright @ 2014

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 24 March 2014
                : 8 October 2014
                Page count
                Pages: 19
                Funding
                The authors have no support or funding to report.
                Categories
                Research Article
                Biology and Life Sciences
                Cell Biology
                Cytology
                Medicine and Health Sciences
                Diagnostic Medicine
                Diagnostic Radiology
                Magnetic Resonance Imaging
                Oncology
                Cancer Treatment
                Physical Sciences
                Physics
                Condensed Matter Physics
                Magnetism
                Magnetic Fields
                Custom metadata
                The authors confirm that all data underlying the findings are fully available without restriction. All relevant data are available on the Figshare website at the following links: http://dx.doi.org/10.6084/m9.figshare.1203566 http://dx.doi.org/10.6084/m9.figshare.1203565 http://dx.doi.org/10.6084/m9.figshare.1203564 http://dx.doi.org/10.6084/m9.figshare.1203562.

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