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Title of Journal: Apoptosis

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Abbravation: Apoptosis

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Springer US

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DOI

10.1002/pu.30136

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ISSN

1573-675X

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Gadolinium induced effects on mammalian cell motil

Authors: Gabor Nagy Viktoria Baksa Alexandra Kiss Melinda Turani Gaspar Banfalvi
Publish Date: 2016/10/22
Volume: 22, Issue: 2, Pages: 188-199
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Abstract

The toxicity of gadolinium is reduced by chelating agents that render this heavy metal into contrast complexes used for medical magnetic resonance imaging However the dissociation of gadolinium chelates is known to generate Gd3+ ions the cellular toxicity of which has not been tested in details The cytotoxic effects of GdIII ions were evaluated by monitoring the proliferation measuring the cellular motility and following chromatin changes in various cell lines upon Gd3+ treatment Measurements applied longterm scanning microscopy and a perfusion platform that replaced the medium with test solutions bypassed physical contact with the cell culture during experiments and provided uninterrupted high timeresolution timelapse photomicrography for an extended period of time Genotoxicity specific chromatin changes characteristic to GdIII were distinguished in human skin keratinocytes HaCaT human limbal stem cells HuLi colorectal adenocarcinoma CaCO2 murine squamous carcinoma SCC and Indian muntjac IM cell lines Characteristic features of GdIII toxicity were loss of cellular motility irreversible attachment of cells to the growth surface and cell death Injuryspecific chromatin changes manifested at micromolar Gd3+ concentrations as premature chromatin condensation and highly condensed sticky chromatin patches GdIII concentration and cell typedependent reduction of normal adherence as well as premature chromatin condensation confirmed apoptosis The risk related to the release of toxic Gd3+ ions from gadolinium complexes and their effects on mono and multilayer cellular barriers have to be reconsidered when these chelated complexes are used as contrasting agents especially in relation to possible blood–brain barrier damages

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