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Öğe Assessment of genetic damage induced by gadolinium-based radiocontrast agents(Elsevier GmbH, 2022) Çobanoğlu, HayalBackground: Today, although gadolinium based contrast agents have been frequently used in the field of medicine, there is limited data available whether gadolinium based agents affect the genome. Aim: The present study aimed to investigate the genotoxic and cytotoxic potentials of gadoteric acid and gadoversetamide used as gadolinium-based contrast agents for magnetic resonance (MR) imaging. Material and methods: The cytokinesis-block micronucleus assay was applied to human peripheral blood lymphocytes to assess the genotoxicity measured as micronucleus (MN), nucleoplasmic bridge (NPBs) and nuclear bud (NBUDs) frequencies. Furthermore, cytokinesis-block proliferation index (CBPI) was calculated to determine cytostasis. Lymphocytes were treated with gadoteric acid at concentrations of 1.0, 2.5, 5.0, and 25 mM and with gadoversetamide at concentrations of 0.25, 1.0, 2.5, and 5.0 mM for 48 h. Results: Gadoteric acid did not cause significant increase in MN, NBPs and NBUDs frequencies and CBPI values at any concentration. Gadoversetamide induced significantly increase MN formation at concentration of 2.5 mM, NBP formation at concentrations of 1.0 and 2.5 mM, and NBUD formation at concentrations of 0.25, 1.0 and 2.5 mM. Additionally, gadoversetamide exposure resulted in statistically significant decrease in CBPI values compared to the control at concentrations of 2.5 and 5.0 mM. In addition, CBPI levels in response to concentrations of gadoversetamide was negatively and significantly associated with concentration. Conclusion: These findings show that gadoteric acid does not have genotoxic or cytotoxic potential, while gadoversetamide might have both genotoxic and cytotoxic potential on human peripheral blood lymphocytes. As a comparison, gadoversetamide was found more genotoxic and cytotoxic.Öğe Assessment of the genotoxic potential of tetrachlorvinphos insecticide by cytokinesis-block micronucleus and sister chromatid exchange assays(SAGE Publications, 2021) Çobanoğlu, Hayal; Çayır, AkınTetrachlorvinphos is an organophosphate that is classified as a carcinogen in humans by several authorities. Due to very limited data regarding the genotoxic potential, we aimed to comprehensively investigate in vitro genotoxic potential of tetrachlorvinphos. We performed our study by applying the cytokinesis-block micronucleus cytome and sister chromatid exchange (SCE) assays to human peripheral blood lymphocytes. We evaluated micronucleus (MN) and SCE frequencies and cytokinesis-block proliferation index in both exposed and non-exposed lymphocytes. We also calculated the chromosomal instability level in response to exposure by combining the results of MN and SCE. We found that MN frequency did not increase with exposure to tetrachlorvinphos (0–50 µg/ml). In contrast, we observed that SCE frequencies significantly increased with exposure to ≥5 µg/ml tetrachlorvinphos. Furthermore, exposure to tetrachlorvinphos at concentrations of 50 µg/ml induced a significant increase in chromosomal instability level (p < 0.05). Cytokinesis-block proliferation index level did not significantly decrease in response to tetrachlorvinphos exposure. Our findings reveal that tetrachlorvinphos resulted in different DNA damages that were measured by two assays. Furthermore, our findings suggested that exposure to tetrachlorvinphos increased chromosomal instability that is a hallmark of many malignancies. We conclude that although tetrachlorvinphos does not significantly increase the MN level, the significant increase of both SCE and CIN frequencies indicates the genotoxic potential of tetrachlorvinphos in human peripheral lymphocytes. Additionally, tetrachlorvinphos is not cytotoxic in the range of tested concentrations.Öğe Evaluation of DNA damages in congenital hearing loss patients(Elsevier B.V., 2021) Çağlar, Özge; Çobanoğlu, Hayal; Uslu, Atilla; Çayır, AkınIn 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) was 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 positively correlated with NBUD frequency which may indicate a common mechanism for these biomarkers in the patient group. We found, for the first time, that there were statistically significant higher levels of MN, NPB, and NBUD in sensorineural hearing loss patients. Since the markers we evaluated were linked with crucial diseases, our findings might suggest that sensorineural hearing loss patients are susceptible to several crucial diseases, especially cancer. Furthermore, the results demonstrated the significance of the MN, NPB, and NBUD level and thus provides a potential marker for the diagnosis of congenital hearing loss patients.Öğe Gadobutrol’ün Sitokinezi Bloke Edilmiş Mikronükleus Tekniği ileGenotoksik ve Sitotoksik Potansiyelinin Değerlendirilmesi(2021) Çobanoğlu, HayalManyetik 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.Öğe Gadoterik Asit’in In Vitro Koşullarda Kardeş Kromatid Değişimi ve Mitotik İndeks ÜzerineEtkisinin Değerlendirilmesi(2021) Çobanoğlu, HayalGadoterik asit manyetik rezonans (MR) görüntülemede teşhis amaçlı kullanılan ekstraselülergadolinyumlu kontrast maddedir. Bu çalışmada gadoterik asit’in insan periferal lenfositlerinde in vitro genotoksik ve sitotoksik etkilerinin değerlendirilmesi amaçlandı. Çalışmada kardeş kromatid değişimi(KKD) yöntemi kullanıldı. KKD genotosisiteyi temsil eden, mitotik indeks (MI) sitotoksisiteyi temsileden parametreler olarak kullanıldı. Gadoteric acid’in 1, 2.5, 5, ve 25 mM konsantrasyonları ile 48 saatmuamele edilmiş insan periferal lenfositlerinde hem genotoksisite hem de sitototoksisite parametrelerideğerlendirildi. Gadoteric acid’in hiçbir konsantrasyonda MI değerleri üzerinde anlamlı bir değişikliğeneden olmadığı, KKD’ni ise sadece en yüksek konsantrasyonda (25 mM) anlamlı derecede arttığı tespitedildi (p<0.05). Bu bulgular gadoterik asit’in sitotoksik bir potansiyelinin olmadığını buna karşın zayıfbir genotoksik potansiyelinin olabileceğine işaret etmektedir.Öğe Genotoxic and cytotoxic effects of polyethylene microplastics on human peripheral blood lymphocytes(Elsevier Ltd, 2021) Çobanoğlu, Hayal; Belivermiş, Murat; Sıkdokur, Ercan; Kılıç, Önder; Çayır, AkınCurrently, 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.Öğe Occupational exposure to radiation among health workers: Genome integrity and predictors of exposure(Elsevier B.V., 2024) Çobanoğlu, Hayal; Çayır, AkınThe current study aimed to investigate genomic instabilities in healthcare workers who may experience varying levels of radiation exposure through various radiological procedures. It also sought to determine if factors related to the work environment and dosimeter reading could effectively explain the observed genomic instabilities. Utilizing the cytokinesis-block micronucleus assay (CBMN) on peripheral blood lymphocytes, we assessed a spectrum of genomic aberrations, including nucleoplasmic bridge (NPB), nuclear budding (NBUD), micronucleus (MN) formation, and total DNA damage (TDD). The study uncovered a statistically significant increase in the occurrence of distinct DNA anomalies among radiology workers (with a significance level of P < 0.0001 for all measurements). Notably, parameters such as total working hours, average work duration, and time spent in projection radiography exhibited significant correlations with MN and TDD levels in these workers. The dosimeter readings demonstrated a positive correlation with the frequency of NPB and NBUD, indicating a substantial association between radiation exposure and these two genomic anomalies. Our multivariable models identified the time spent in projection radiography as a promising parameter for explaining the overall genomic instability observed in these professionals. Thus, while dosimeters alone may not fully explain elevated total DNA damage, intrinsic work environment factors hold potential in indicating exposure levels for these individuals, providing a complementary approach to monitoring.
