Concentration-Dependent Cytotoxicity and DNA Damage Responses of Iohexol in MCF-7 Breast Cancer Cells: An In Vitro...

Iohexol is a nonionic, low-osmolarity iodinated contrast agent that is widely used in clinical imaging applications. This study evaluated the cytotoxic effects and DNA damage responses of iohexol on the human breast adenocarcinoma cell line (MCF-7) in vitro using MTS and alkaline comet assays. Additionally, molecular docking analyses were performed to complement this approach and investigate the potential interactions of iohexol with DNA, the anti-apoptotic protein BCL-XL, and the metabolic enzyme NUDT5. Iohexol administration caused a concentration-dependent decrease in cell viability, with significant cytotoxicity observed at concentrations of ≥ 18.26 mM (p < 0.0001). Comet assay results showed increased DNA damage responses at concentrations above clinical doses, with significant increases detected from 22.8 mM onwards (p < 0.05) and the highest damage levels observed at 91.3-182.6 mM (p < 0.01). Molecular docking analyses revealed that iohexol exhibited weak binding affinity with DNA (-3.57 kcal/mol), showing relatively more pronounced, albeit still moderate, interactions with BCL-XL (-5.25 kcal/mol) and NUDT5 (-5.40 kcal/mol). These findings suggest that iohexol may indirectly interact via pathways associated with cellular stress. In general, the obtained data indicate that iohexol can cause cytotoxicity and DNA damage responses in MCF-7 cells under supra-clinical in vitro exposure conditions. These findings suggest that these effects develop through indirect cellular mechanisms rather than direct DNA binding. This emphasizes the need for careful interpretation of high-dose in vitro data, as well as the need for further mechanistic studies, in order to better understand the cellular effect profile of iohexol. Therefore, the present findings should not be interpreted as direct evidence of genotoxic risk under clinically relevant exposure conditions.