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Gadobutrol’ün Sitokinezi Bloke Edilmiş Mikronükleus Tekniği ile Genotoksik ve Sitotoksik Potansiyelinin Değerlendirilmesi

Manyetik rezonans (MR) tıpta yaygın olarak kullanılan bir görüntüleme tekniğidir. Günümüzde dünya genelinde yapılan MR çekimlerin %40 kontrast madde kullanılarak yapılmaktadır. Bu çalışmaya araştırma konusu olan gadobutrol MR görüntülemede kullanılan non iyonik, makrosiklik ve gadolinyum bazlı bir kontrast maddedir. Bu çalışmada in vitro koşullarda insan periferal lenfositlerinde gadobutrol’ün genotoksik ve sitotoksik potansiyelinin olup olmadığı araştırıldı. Çalışmada genotoksisite değerlendirilmelerinde sıklıkla kullanılan sitokinezi bloke edilmiş mikronükleus yöntemi kullanıldı. Gönüllü donörlerden alınan periferal kan örneği ilacın 3 farklı konsantrasyonu (1, 5, 25 mM) ile 48 saat muamele edildi. Elde edilen sonuçlar, mikronükleus sıklığı bakımından tüm konsantrasyonlarda artış olduğunu ancak 5 ve 25 mM’lık konsantrasyondaki artışın istatistiksel olarak anlamlı olduğunu gösterdi (p˂0.05; p˂0.01 sırasıyla). Nükleoplasmik köprü ve nüklear bud sıklıklarında negatif kontrole göre anlamlı bir farklılık görülmedi (p˃0.05). İlacın sitostatik etki bakımından da kontrole göre anlamlı bir değişikliğe neden olmadığı tespit edildi (p˃0.05). Bu bulgular gadobutrol’ün sitotoksik bir potansiyelinin olmadığını ancak genotoksik potansiyelinin olabileceğini göstermektedir.

Anahtar Kelimeler:

Gadobutrol, mikronükleus, nükleoplasmik köprü, nüklear bud, sitotoksisite

Assesment of Genotoxic and Cytotoxic Potential of Gadobutrol by Using Cytokinesis-Blocked Micronucleus Assay

Magnetic resonance is an imaging technique widely used in medicine. Today worldwide 40% of magnetic resonance imaging is made using contrast agent. Gadobutrol is a nonionic, macrocyclic and gadolinium based contrast agent for magnetic resonance imaging. In this in vitro study, it was aimed to investigate whether Gadobutrol has genotoxic and cytotoxic effects on human peripheral lymphocyte In the study, cytokinesis-blocked micronucleus assay, which is frequently used in evaluating genotoxicity, was used. Peripheral blood samples from volunteer donors were treated with 3 different concentrations of the drug (1, 5, 25 mM) for 48 hours. The MN frequency caused by each concentration of gadobutrol was found to be higher than the negative control, but the increase in concentration of 5 and 25 mM was statistically significant (p˂0.05; p˂0.01 respectively). At the studied concentrations, nucleoplasmic bridge and nuclear bud values were not significant (p>0.05). It was determined that gadobutrol did not cause a significant change in terms of cytostatic values compared to control. These findings suggest that gadobutrol was non-cytotoxic but potentially genotoxic.

Keywords:

Gadobutrol, micronucleus, nucleoplasmic bridge, nuclear bud, cytotoxicity,

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1-https://www.oecd-ilibrary.org/social-issues-migration-health/magnetic-resonance-imaging-mri-exams-total-2014-1_mri-exam-total-table-2014-1-en (04.02.2021)
2-https://www.saglikaktuel.com/d/file/35c966a9f1d343909d4d0858bec69333.pdf (04.02.2021)