Araştırma Makalesi
BibTex RIS Kaynak Göster

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

Yıl 2021, Cilt: 21 Sayı: 3, 532 - 537, 30.06.2021
https://doi.org/10.35414/akufemubid.876727

Öz

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.

Kaynakça

  • Azimi, S., Mozdarani, H. and Mahmoudzadeh, A., 2017. Induction of DNA damage, apoptosis and micronuclei in peripheral blood lymphocytes following injection of contrast media in patients with abdominal CT scan. International Journal of Radiation Research, 15(2), 149-55.
  • Battal, D., Aktas, A., Sungur, MA., Kadioglu, E., Derici, EE., Sahin, NO. and Saygı, S., 2013. In vivo genotoxicity assessment of sertraline by using alkaline comet assay and the cytokinesis‐block micronucleus assay. Basic & Clinical Pharmacology & Toxicology, 113(5), 339-46.
  • Bolognesi, C., 2003. Genotoxicity of pesticides: a review of human biomonitoring studies. Mutation Research, 543(3), 251-72.
  • Bolognesi, C., Creus, A., Ostrosky, WP. and Marcos, R., 2011. Micronuclei and pesticide exposure. Mutagenesis, 26(1), 19-26.
  • Cobanoglu, H., Coskun, M., Çayir, A. and Coskun, M., 2018. In vitro genotoxic and cytotoxic effects of doxepin and escitalopram on human peripheral lymphocytes. Drug and Chemical Toxicology, 41(2), 238-44.
  • Cayir, A., Cobanoglu, H. and Coskun, M., 2020. Assessment of the genotoxic potential of a migraine-specific drug by comet and cytokinesis-block micronucleus assays. Expert Opinion on Drug Metabolism & Toxicology, 16(5), 441-6.
  • Eastmond, DA. and Tucker, JD., 1989. Identification of aneuploidy‐inducing agents using cytokinesis‐blocked human lymphocytes and an antikinetochore antibody. Environmental and Molecular Mutagenesis, 13(1), 34-43.
  • Fenech, M., 2002. Chromosomal biomarkers of genomic instability relevant to cancer. Drug Discovery Today, 7(22), 1128-37.
  • Fenech, M., 2006. Cytokinesis-block micronucleus assay evolves into a “cytome” assay of chromosomal instability, mitotic dysfunction and cell death. Mutation Research Fundamental and Molecular Mechanisms of Mutagenesis, 600(1-2), 58-66.
  • Fenech, M., 2007. Cytokinesis-block micronucleus cytome assay. Nature Protocols, 2(5), 1084.
  • Fenech, M., Chang, WP., Kirsch-Volders, M., Holland, N., Bonassi, S. and Zeiger, E., 2003. HUMN Project: detailed description of the scoring criteria for the cytokinesis-block micronucleus assay using isolated human lymphocyte cultures. Mutation Research Genetic Toxicology and Environmental Mutagenesis, 534(1-2), 65-75.
  • Fenech, M., 2000. The in vitro micronucleus technique. Mutation Research, 455, 81–95.
  • Fiechter, M., Stehli, J., Fuchs, TA., Dougoud, S., Gaemperli, O. and Kaufmann, PA., 2013. Impact of cardiac magnetic resonance imaging on human lymphocyte DNA integrity. European Heart Journal, 34(30), 2340-5.
  • Hill, MA., 2018. Cardiac MR imaging genotoxicity? European Heart Journal, 39, 313–315.
  • Kirsch-Volders, M., Sofuni, T., Aardema, M., Albertini, S., Eastmond, D., Fenech M., Ishidate, M., Kirchner, S., Lorge, E., Morita, T., Norppa, H., Surrallés, J., Vanhauwaert, A. and Wakata, A., 2003. Report from the in vitro micronucleus assay working group. Mutation Research, 540, 153–163.
  • Lorge, E., Hayashi, M., Albertini, S. and Kirkland, D., 2008. Comparison of different methods for an accurate assessment of cytotoxicity in the in vitro micronucleus test: I. Theoretical aspects. Mutation Research Genetic Toxicology and Environmental Mutagenesis, 655(1-2), 1-3.
  • Morcos, SK., 2008. Extracellular gadolinium contrast agents: differences in stability. European Journal of Radiology, 66, 175–179.
  • Parvez, Z., Kormano, M., Moncada, R. and Eklund, R., 1986. Contrast media-induced chromosomal damage in human lymphocyte cultures. Investigative Radiology, 21(11), 864-9.
  • Parant, M., Sohm, B., Flaya, J., Perrat, E., Chuburu, F., Cadiou, C., Rosin, C. and Cossu-Leguille, C., 2019. Impact of gadolinium-based contrast agents on the growth of fish cells lines. Ecotoxicology and Environmental Safety, 182, 1-7.
  • Reddig, A., Fatahi, M., Roggenbuck, D., Ricke, J., Reinhold, D., Speck, O. and Björn, F., 2017. Impact of in vivo high-field-strength and ultra-high-field-strength MR imaging on DNA double-strand-break formation in human lymphocytes. Radiology, 282(3), 782-9.
  • Roshdy, HM. and Shoman, TM., 2004. Cytogenetic and developmental effects of antidepression drug (Cipralex) on female mice and embryos. The Egyptian Journal of Hospital Medicine, 17(1), 63-9.
  • Simi, S., Ballardin, M., Casella, M., De Marchi, D., Hartwig, V., Giovannetti, G., Vanelloc, N., Gabbriellini, S., Landinic, L. and Lombardi, M., 2008. Is the genotoxic effect of magnetic resonance negligible? Low persistence of micronucleus frequency in lymphocytes of individuals after cardiac scan. Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis, 645(1-2), 39-43.
  • Tazehkand, MN. and Topaktas, M., 2015. The in vitro genotoxic and cytotoxic effects of remeron on human peripheral blood lymphocytes. Drug and Chemical Toxicology, 38(3), 266-71.
  • Wack, C., Steger-Hartmann, T., Mylecraine, L. and Hofmeister, R., 2012. Toxicological safety evaluation of gadobutrol. Investigative Radiology, 47(11), 611-623.
  • Xia, Q., Feng, X., Huang, H., Du, L., Yang, X. and Wang, K., 2011. Gadolinium‐induced oxidative stress triggers endoplasmic reticulum stress in rat cortical neurons. Journal of Neurochemistry, 117, 38-47.
  • 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)

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

Yıl 2021, Cilt: 21 Sayı: 3, 532 - 537, 30.06.2021
https://doi.org/10.35414/akufemubid.876727

Öz

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.

Kaynakça

  • Azimi, S., Mozdarani, H. and Mahmoudzadeh, A., 2017. Induction of DNA damage, apoptosis and micronuclei in peripheral blood lymphocytes following injection of contrast media in patients with abdominal CT scan. International Journal of Radiation Research, 15(2), 149-55.
  • Battal, D., Aktas, A., Sungur, MA., Kadioglu, E., Derici, EE., Sahin, NO. and Saygı, S., 2013. In vivo genotoxicity assessment of sertraline by using alkaline comet assay and the cytokinesis‐block micronucleus assay. Basic & Clinical Pharmacology & Toxicology, 113(5), 339-46.
  • Bolognesi, C., 2003. Genotoxicity of pesticides: a review of human biomonitoring studies. Mutation Research, 543(3), 251-72.
  • Bolognesi, C., Creus, A., Ostrosky, WP. and Marcos, R., 2011. Micronuclei and pesticide exposure. Mutagenesis, 26(1), 19-26.
  • Cobanoglu, H., Coskun, M., Çayir, A. and Coskun, M., 2018. In vitro genotoxic and cytotoxic effects of doxepin and escitalopram on human peripheral lymphocytes. Drug and Chemical Toxicology, 41(2), 238-44.
  • Cayir, A., Cobanoglu, H. and Coskun, M., 2020. Assessment of the genotoxic potential of a migraine-specific drug by comet and cytokinesis-block micronucleus assays. Expert Opinion on Drug Metabolism & Toxicology, 16(5), 441-6.
  • Eastmond, DA. and Tucker, JD., 1989. Identification of aneuploidy‐inducing agents using cytokinesis‐blocked human lymphocytes and an antikinetochore antibody. Environmental and Molecular Mutagenesis, 13(1), 34-43.
  • Fenech, M., 2002. Chromosomal biomarkers of genomic instability relevant to cancer. Drug Discovery Today, 7(22), 1128-37.
  • Fenech, M., 2006. Cytokinesis-block micronucleus assay evolves into a “cytome” assay of chromosomal instability, mitotic dysfunction and cell death. Mutation Research Fundamental and Molecular Mechanisms of Mutagenesis, 600(1-2), 58-66.
  • Fenech, M., 2007. Cytokinesis-block micronucleus cytome assay. Nature Protocols, 2(5), 1084.
  • Fenech, M., Chang, WP., Kirsch-Volders, M., Holland, N., Bonassi, S. and Zeiger, E., 2003. HUMN Project: detailed description of the scoring criteria for the cytokinesis-block micronucleus assay using isolated human lymphocyte cultures. Mutation Research Genetic Toxicology and Environmental Mutagenesis, 534(1-2), 65-75.
  • Fenech, M., 2000. The in vitro micronucleus technique. Mutation Research, 455, 81–95.
  • Fiechter, M., Stehli, J., Fuchs, TA., Dougoud, S., Gaemperli, O. and Kaufmann, PA., 2013. Impact of cardiac magnetic resonance imaging on human lymphocyte DNA integrity. European Heart Journal, 34(30), 2340-5.
  • Hill, MA., 2018. Cardiac MR imaging genotoxicity? European Heart Journal, 39, 313–315.
  • Kirsch-Volders, M., Sofuni, T., Aardema, M., Albertini, S., Eastmond, D., Fenech M., Ishidate, M., Kirchner, S., Lorge, E., Morita, T., Norppa, H., Surrallés, J., Vanhauwaert, A. and Wakata, A., 2003. Report from the in vitro micronucleus assay working group. Mutation Research, 540, 153–163.
  • Lorge, E., Hayashi, M., Albertini, S. and Kirkland, D., 2008. Comparison of different methods for an accurate assessment of cytotoxicity in the in vitro micronucleus test: I. Theoretical aspects. Mutation Research Genetic Toxicology and Environmental Mutagenesis, 655(1-2), 1-3.
  • Morcos, SK., 2008. Extracellular gadolinium contrast agents: differences in stability. European Journal of Radiology, 66, 175–179.
  • Parvez, Z., Kormano, M., Moncada, R. and Eklund, R., 1986. Contrast media-induced chromosomal damage in human lymphocyte cultures. Investigative Radiology, 21(11), 864-9.
  • Parant, M., Sohm, B., Flaya, J., Perrat, E., Chuburu, F., Cadiou, C., Rosin, C. and Cossu-Leguille, C., 2019. Impact of gadolinium-based contrast agents on the growth of fish cells lines. Ecotoxicology and Environmental Safety, 182, 1-7.
  • Reddig, A., Fatahi, M., Roggenbuck, D., Ricke, J., Reinhold, D., Speck, O. and Björn, F., 2017. Impact of in vivo high-field-strength and ultra-high-field-strength MR imaging on DNA double-strand-break formation in human lymphocytes. Radiology, 282(3), 782-9.
  • Roshdy, HM. and Shoman, TM., 2004. Cytogenetic and developmental effects of antidepression drug (Cipralex) on female mice and embryos. The Egyptian Journal of Hospital Medicine, 17(1), 63-9.
  • Simi, S., Ballardin, M., Casella, M., De Marchi, D., Hartwig, V., Giovannetti, G., Vanelloc, N., Gabbriellini, S., Landinic, L. and Lombardi, M., 2008. Is the genotoxic effect of magnetic resonance negligible? Low persistence of micronucleus frequency in lymphocytes of individuals after cardiac scan. Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis, 645(1-2), 39-43.
  • Tazehkand, MN. and Topaktas, M., 2015. The in vitro genotoxic and cytotoxic effects of remeron on human peripheral blood lymphocytes. Drug and Chemical Toxicology, 38(3), 266-71.
  • Wack, C., Steger-Hartmann, T., Mylecraine, L. and Hofmeister, R., 2012. Toxicological safety evaluation of gadobutrol. Investigative Radiology, 47(11), 611-623.
  • Xia, Q., Feng, X., Huang, H., Du, L., Yang, X. and Wang, K., 2011. Gadolinium‐induced oxidative stress triggers endoplasmic reticulum stress in rat cortical neurons. Journal of Neurochemistry, 117, 38-47.
  • 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)
Toplam 27 adet kaynakça vardır.

Ayrıntılar

Birincil Dil Türkçe
Konular Mühendislik
Bölüm Makaleler
Yazarlar

Hayal Çobanoğlu 0000-0001-9640-3354

Yayımlanma Tarihi 30 Haziran 2021
Gönderilme Tarihi 8 Şubat 2021
Yayımlandığı Sayı Yıl 2021 Cilt: 21 Sayı: 3

Kaynak Göster

APA Çobanoğlu, H. (2021). Gadobutrol’ün Sitokinezi Bloke Edilmiş Mikronükleus Tekniği ile Genotoksik ve Sitotoksik Potansiyelinin Değerlendirilmesi. Afyon Kocatepe Üniversitesi Fen Ve Mühendislik Bilimleri Dergisi, 21(3), 532-537. https://doi.org/10.35414/akufemubid.876727
AMA Çobanoğlu H. Gadobutrol’ün Sitokinezi Bloke Edilmiş Mikronükleus Tekniği ile Genotoksik ve Sitotoksik Potansiyelinin Değerlendirilmesi. Afyon Kocatepe Üniversitesi Fen Ve Mühendislik Bilimleri Dergisi. Haziran 2021;21(3):532-537. doi:10.35414/akufemubid.876727
Chicago Çobanoğlu, Hayal. “Gadobutrol’ün Sitokinezi Bloke Edilmiş Mikronükleus Tekniği Ile Genotoksik Ve Sitotoksik Potansiyelinin Değerlendirilmesi”. Afyon Kocatepe Üniversitesi Fen Ve Mühendislik Bilimleri Dergisi 21, sy. 3 (Haziran 2021): 532-37. https://doi.org/10.35414/akufemubid.876727.
EndNote Çobanoğlu H (01 Haziran 2021) Gadobutrol’ün Sitokinezi Bloke Edilmiş Mikronükleus Tekniği ile Genotoksik ve Sitotoksik Potansiyelinin Değerlendirilmesi. Afyon Kocatepe Üniversitesi Fen Ve Mühendislik Bilimleri Dergisi 21 3 532–537.
IEEE H. Çobanoğlu, “Gadobutrol’ün Sitokinezi Bloke Edilmiş Mikronükleus Tekniği ile Genotoksik ve Sitotoksik Potansiyelinin Değerlendirilmesi”, Afyon Kocatepe Üniversitesi Fen Ve Mühendislik Bilimleri Dergisi, c. 21, sy. 3, ss. 532–537, 2021, doi: 10.35414/akufemubid.876727.
ISNAD Çobanoğlu, Hayal. “Gadobutrol’ün Sitokinezi Bloke Edilmiş Mikronükleus Tekniği Ile Genotoksik Ve Sitotoksik Potansiyelinin Değerlendirilmesi”. Afyon Kocatepe Üniversitesi Fen Ve Mühendislik Bilimleri Dergisi 21/3 (Haziran 2021), 532-537. https://doi.org/10.35414/akufemubid.876727.
JAMA Çobanoğlu H. Gadobutrol’ün Sitokinezi Bloke Edilmiş Mikronükleus Tekniği ile Genotoksik ve Sitotoksik Potansiyelinin Değerlendirilmesi. Afyon Kocatepe Üniversitesi Fen Ve Mühendislik Bilimleri Dergisi. 2021;21:532–537.
MLA Çobanoğlu, Hayal. “Gadobutrol’ün Sitokinezi Bloke Edilmiş Mikronükleus Tekniği Ile Genotoksik Ve Sitotoksik Potansiyelinin Değerlendirilmesi”. Afyon Kocatepe Üniversitesi Fen Ve Mühendislik Bilimleri Dergisi, c. 21, sy. 3, 2021, ss. 532-7, doi:10.35414/akufemubid.876727.
Vancouver Çobanoğlu H. Gadobutrol’ün Sitokinezi Bloke Edilmiş Mikronükleus Tekniği ile Genotoksik ve Sitotoksik Potansiyelinin Değerlendirilmesi. Afyon Kocatepe Üniversitesi Fen Ve Mühendislik Bilimleri Dergisi. 2021;21(3):532-7.