Assesment of genotoxic and cytotoxic potential of gadobutrol by using cytokinesis-blocked micronucleus assay

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.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

Evaluation of DNA damages in congenital hearing loss patients

In the current study, we aimed to compare the level of genetic damages measured as micronucleus (MN), nucleoplasmic bridge (NPB), and nuclear bud formation (NBUD) in congenital hearing loss patients (n = 17) and control group (n = 24). The cytokinesis-blocked micronucleus assay (CBMN) as applied to the blood samples to measure the frequency of the markers in both groups. The frequencies of MN of hearing loss patients were found to be consistently significantly higher than those obtained for the control group (p < 0.0001). Similarly, we found significantly higher frequency of NPB in patients was obtained for the patient group (p < 0.0001). Finally, the frequencies of NBUD in patients is significantly higher than the level measured in the control group (p < 0.0001). Furthermore, the age-adjusted MNL, BNMN, NPB, and NBUD frequencies in the patients were significantly higher than those obtained in the control group. We observed that the frequency of MN in patients was positivelycorrelated with NBUD frequency which may indicate a common mechanism for these biomarkers in the patientgroup. We found, for the first time, that there were statistically significant higher levels of MN, NPB, and NBUDin sensorineural hearing loss patients. Since the markers we evaluated were linked with crucial diseases, ourfindings might suggest that sensorineural hearing loss patients are susceptible to several crucial diseases, espe-cially cancer. Furthermore, the results demonstrated the significance of the MN, NPB, and NBUD level and thusprovides a potential marker for the diagnosis of congenital hearing loss patients

Genotoxic and cytotoxic effects of polyethylene microplastics on human peripheral blood lymphocytes

© 2021 Elsevier LtdCurrently, we need emerging initial data regarding how plastic exposures affect cellular and molecular components and how such interactions will be crucial for human health. We aimed to determine the genotoxic and cytotoxic effects of microplastic (MPs,10-45 μm, polyethylene) on human peripheral lymphocytes by using the cytokinesis-block micronucleus cytome (CBMN) assay, which is a comprehensive method to reveal a range of mechanisms, not only diseases but also response to environmental exposures. We measured micronucleation (MN), nucleoplasmic bridge formation (NPB), and nuclear bud formation (NBUD) in human peripheral blood lymphocytes. We also measured the cytokinesis-block proliferation index (CBPI) to calculate cytostasis, which indicates cytotoxicity in lymphocytes treated with five different MPs concentrations for 48 h. Even lower concentrations of MPs increased the level of genomic instability. We found that the in vitro MP exposure significantly increased MN, NPB, and NBUD frequencies. Since we investigated the effect of larger particles relative to the lymphocytes, mechanic interaction of MPs with cells, the release of monomer and additives from MPs could be suggested as possible mechanisms accounting for increasing genomic instabilities. We did not observe a decrease in the cell proliferation index, indicating a lack of MPs’ cytotoxic potential. To the best of our knowledge, our study is the first to identify MPs’ genotoxic potential in human peripheral blood lymphocytes. We suggested further studies to investigate the genotoxic and cytotoxic potential of smaller plastics and the chronic effect of MP on the human population