In vitro cytogenotoxic evaluation of gadobutrol on mcf-7 cell line and computational molecular docking analysis

Background: Gadobutrol (Gd) is a highly water-soluble, hydrophilic gadolinium-based (Gd-based) contrast agent with thermodynamic stability, bound to a non-ionic, macrocyclic hard chelate complex. The aim of this study was to evaluate the possible genocytotoxic effects of gadobutrol, which is widely used worldwide, in breast cancer cells (MCF-7). Furthermore, the interaction energy level of gadobutrol with B-DNA was evaluated in silico using molecular docking. Methods: Gadobutrol (0.1 mM, 1 mM, 10 mM and 100 mM) was applied to MCF-7 cells and the decrease in cell viability and IC 50 dose were evaluated by 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) method. After determining the IC 50 values of gadobutrol (3.31 mM, 6.63 mM, 13.27 mM and 26.54 mM), the genotoxic effects of gadobutrol on MCF-7 cells were examined using Comet assay. Furthermore, a molecular docking experiment was performed using Schrödinger Maestro 13.9 to predict the possible interaction of gadobutrol in the crystal structures of the B-DNA molecule. Results: All concentrations of gadobutrol did not cause a statistically significant change in terms of genotoxic effect in MCF-7 cells (ns p > 0.05). However, all concentrations applied for MTS statistically significantly decreased cell viability in MCF-7 cells (**p < 0.01 and ****p < 0.0001, respectively). According to the results of in silico analysis; Gadobutrol is located in the minor groove of DNA. Hydrogen bonds were formed between the hydroxyl groups of the molecule and DNA bases and the free binding energy was determined as -6.14 kcal/mol. Conclusions: According to the results of the study carried out under in vitro conditions, it was determined that gadobutrol used in MRI imaging did not show genotoxic effects but statistically decreased cell viability. In addition, the interaction of gadobutrol with B-DNA suggested that it may induce apoptosis in MCF-7 cells. The cytogenotoxic effect of gadobutrol in MCF-7 cells may indicate a promising new strategy for breast cancer treatment.