Gadobutrol'ün mcf-7 hücre hattı üzerinde in vitro sitogenotoksik değerlendirmesi ve hesaplamalı moleküler doklama analizi

Year 2025, Volume: 6 Issue: 3, 226 - 234, 28.09.2025

İbrahim Halil Kenger , Batuhan Bilgin

https://doi.org/10.47482/acmr.1643905

Abstract

Arka plan: Gadobutrol, iyonik olmayan, makrosiklik sert bir şelat kompleksine bağlı, termodinamik stabiliteye sahip, suda yüksek oranda çözünebilen, hidrofilik gadolinyum bazlı bir kontrast ajandır. Bu çalışmanın amacı, dünya çapında yaygın olarak kullanılan gadobutrolün mcf-7 hücrelerindeki olası genositotoksik etkilerini değerlendirmektir. Ayrıca, gadobutrolün B-DNA ile etkileşim enerji seviyesi moleküler yerleştirme kullanılarak in silico olarak değerlendirilmiştir.
Gereç ve Yöntemler: Gadobutrol (0.1 mM, 1 mM, 10 mM ve 100 mM) mcf-7 hücrelerine uygulanmış ve hücre canlılığındaki azalma ve IC 50 dozu 3-(4,5-dimetiltiyazol-2-il)-5-(3-karboksimetoksifenil)-2-(4-sülfofenil)-2H-tetrazolyum (MTS) yöntemi ile değerlendirilmiştir. Gadobutrolün IC 50 değerleri (3.31 mM, 6.63 mM, 13.27 mM ve 26.54 mM) belirlendikten sonra, gadobutrolün mcf-7 hücreleri üzerindeki genotoksik etkileri Comet testi kullanılarak incelenmiştir. Ayrıca, B-DNA molekülünün kristal yapılarında gadobutrolün olası etkileşimini tahmin etmek için Schrödinger Maestro 13.9 kullanılarak bir moleküler yerleştirme deneyi gerçekleştirilmiştir.
Sonuçlar: Gadobutrolün tüm konsantrasyonları mcf-7 hücrelerinde genotoksik etki açısından istatistiksel olarak anlamlı bir değişikliğe neden olmamıştır. Ancak mts için uygulanan tüm konsantrasyonlar mcf-7 hücrelerinde hücre canlılığını istatistiksel olarak anlamlı şekilde azaltmıştır (sırasıyla p < 0.01 ve p < 0.0001). In slico analiz sonuçlarına göre; Gadobutrol DNA'nın minör oluğunda yer almaktadır. Molekülün hidroksil grupları ile DNA bazları arasında hidrojen bağları oluşmuş ve serbest bağlanma enerjisi -6.14 kcal/mol olarak belirlenmiştir.
Sonuçlar: İn vitro koşullarda gerçekleştirilen çalışmanın sonuçlarına göre MR görüntülemede kullanılan gadobutrolün genotoksik etki göstermediği ancak hücre canlılığını istatistiksel olarak azalttığı belirlenmiştir. Ayrıca gadobutrolün B-DNA ile etkileşimi MCF-7 hücrelerini apoptoza sürükleyebileceğini düşündürmüştür. Gadobutrolün MCF-7 hücrelerindeki sitogenotoksik etkisi, meme kanseri tedavisi için umut verici yeni bir stratejiye işaret edebilir.

Keywords

kanser , MCF-7 hücre hattı , Gadobutrol , sitotoksisite , genotoksisite , in siliko moleküler yerkeştirme

Ethical Statement

Etik kurul izni gerekmemektedir

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

Abstract

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.

Keywords

cancer , MCF-7 cell line , gadobutrol , Cytotoxicity , Genotoxicity , İn slico molecular docking

Ethical Statement

No ethics committee authorisation required

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