title: Gadolinium induced effects on mammalian cell motility, adherence and chromatin structure.
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 Gd(III) ions were evaluated by monitoring the proliferation, measuring the cellular motility and following chromatin changes in various cell lines upon Gd3+treatment. Measurements applied long-term 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 time-resolution time-lapse photomicrography for an extended period of time. Genotoxicity specific chromatin changes characteristic to Gd(III) 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 Gd(III) toxicity were: loss of cellular motility, irreversible attachment of cells to the growth surface and cell death. Injury-specific chromatin changes manifested at micromolar Gd3+concentrations as premature chromatin condensation and highly condensed sticky chromatin patches. Gd(III) concentration- and cell type-dependent 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 multi-layer cellular barriers have to be reconsidered when these chelated complexes are used as contrasting agents especially in relation to possible blood-brain barrier damages.
authors: Department of Biotechnology and Microbiology, University of Debrecen, 1 Egyetem Square, Debrecen, 4010, Hungary. bigdegu@gmail.com.
authors: Gabor
authors: http://orcid.org/0000-0003-1906-0188
authors: G
authors: Nagy
authors: Department of Biotechnology and Microbiology, University of Debrecen, 1 Egyetem Square, Debrecen, 4010, Hungary.
authors: Viktoria
authors: V
authors: Baksa
authors: Department of Biotechnology and Microbiology, University of Debrecen, 1 Egyetem Square, Debrecen, 4010, Hungary.
authors: Alexandra
authors: A
authors: Kiss
authors: Department of Biotechnology and Microbiology, University of Debrecen, 1 Egyetem Square, Debrecen, 4010, Hungary.
authors: Melinda
authors: M
authors: Turani
authors: Department of Biotechnology and Microbiology, University of Debrecen, 1 Egyetem Square, Debrecen, 4010, Hungary.
authors: Gaspar
authors: G
authors: Banfalvi
mesh_terms: D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D018938:Caco-2 Cells; D002465:Cell Movement / Q000187:drug effects*; D002614:Chelating Agents / Q000737:chemistry / Q000494:pharmacology; D002843:Chromatin / Q000187:drug effects; D003287:Contrast Media / Q000009:adverse effects / Q000627:therapeutic use; D005682:Gadolinium / Q000737:chemistry / Q000633:toxicity*; D006801:Humans; D008279:Magnetic Resonance Imaging; D019216:Metals, Heavy / Q000633:toxicity*
chemical_list: D002614:Chelating Agents; D002843:Chromatin; D003287:Contrast Media; D019216:Metals, Heavy; D005682:Gadolinium
keywords: Cell adhesion; Chromatin condensation; Fluorescence microscopy; Perfusion cell culture; Time-lapse microscopy