Gadolinium induced effects on mammalian cell motility, adherence and chromatin structure

Area of Science:

• Biomedical Sciences
• Toxicology
• Cell Biology

Background:

• Gadolinium-based contrast agents (GBCAs) are used in medical imaging.
• Chelating agents reduce gadolinium toxicity, but dissociation can release toxic Gd³⁺ ions.
• The detailed cellular toxicity of free Gd³⁺ ions remains largely uncharacterized.

Purpose of the Study:

• To evaluate the cytotoxic effects of free gadolinium ions (Gd³⁺).
• To investigate Gd³⁺-induced changes in cell proliferation, motility, and chromatin structure.
• To assess Gd³⁺ toxicity across diverse human and animal cell lines.

Main Methods:

• Utilized long-term scanning microscopy and a perfusion platform for high time-resolution cell monitoring.
• Assessed cell proliferation, motility, and chromatin alterations in response to Gd³⁺ treatment.
• Examined genotoxicity-specific chromatin changes in human keratinocytes (HaCaT), limbal stem cells (HuLi), colorectal adenocarcinoma (CaCO₂), murine squamous carcinoma (SCC), and Indian muntjac (IM) cells.

Main Results:

• Gd³⁺ exposure led to loss of cellular motility, irreversible cell attachment, and cell death.
• Characteristic genotoxicity-specific chromatin changes, including premature condensation and sticky chromatin patches, were observed.
• Apoptosis was confirmed by reduced cell adherence and premature chromatin condensation, occurring at micromolar Gd³⁺ concentrations.
• Effects were dependent on Gd³⁺ concentration and cell type.

Conclusions:

• Free Gd³⁺ ions exhibit significant cellular toxicity, affecting cell viability and integrity.
• Gd³⁺ induces characteristic genotoxic chromatin alterations and apoptosis.
• The potential risks of Gd³⁺ release from GBCAs, particularly concerning cellular barriers like the blood-brain barrier, warrant reconsideration.