Evaluation of Gadoteric Acid's Effect on Sister Chromatid Exchange and Mitotic Index Under In Vitro Conditions

Yıl 2021, Cilt: 11 Sayı: 3, 1803 - 1808, 01.09.2021

Hayal Çobanoğlu

https://doi.org/10.21597/jist.876834

Öz

Gadoteric acid is extracellular gadolinium based contrast agent used for diagnostic purposes in magnetic resonance (MR) imaging. In this study, it was aimed to evaluate the in vitro genotoxic and cytotoxic effects of gadoteric acid on human peripheral lymphocytes. Sister chromatid exchange (SCE) was used in the study. SCE and mitotic index (MI) were used as genotoxicity and cytotoxicity parameters respectively. Both genotoxicity and cytototoxicity parameters were evaluated in human peripheral lymphocytes treated with 1, 2.5, 5, and 25 mM concentrations of gadoteric acid for 48 hours. It was determined that gadoteric acid did not cause a significant change on MI values at any concentration and SCE values increased significantly only at the highest concentration (25 mM). These findings indicate that gadoteric acid does not have a cytotoxic potential, but it may have a weak genotoxic potential.

Anahtar Kelimeler

Gadoteric acid, sister chromatid exchange, mitotic index

Gadoterik Asit’in In Vitro Koşullarda Kardeş Kromatid Değişimi ve Mitotik İndeks Üzerine Etkisinin Değerlendirilmesi

Öz

Gadoterik asit manyetik rezonans (MR) görüntülemede teşhis amaçlı kullanılan ekstraselüler gadolinyumlu 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 temsil eden parametreler olarak kullanıldı. Gadoteric acid’in 1, 2.5, 5, ve 25 mM konsantrasyonları ile 48 saat muamele edilmiş insan periferal lenfositlerinde hem genotoksisite hem de sitototoksisite parametreleri değerlendirildi. Gadoteric acid’in hiçbir konsantrasyonda MI değerleri üzerinde anlamlı bir değişikliğe neden olmadığı, KKD’ni ise sadece en yüksek konsantrasyonda (25 mM) anlamlı derecede arttığı tespit edildi (p<0.05). Bu bulgular gadoterik asit’in sitotoksik bir potansiyelinin olmadığını buna karşın zayıf bir genotoksik potansiyelinin olabileceğine işaret etmektedir.

Anahtar Kelimeler

Gadoterik asit, kardeş kromatid değişimi, mitotik indeks

Kaynakça

• Referans1 Azimi S, Mozdarani H, 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): 149-155.
• Referans2 Bau M, Knappe A, Dulski P, 2006. Anthropogenic Gadolinium as a Micropollutant in River Waters in Pennsylvania and in Lake Erie, Northeastern United States. Chemie der Erde Geochemistry, 66: 143-152.
• Referans3 Brand M, Ellmann S, Sommer M, May M S, Eller A, Wuest W, Engert C, Achenbach S, Kuefner M A, Baeuerle T, Lell M, Uder M, 2015. Influence of Cardiac MR Imaging on DNA Double-Strand Breaks in Human Blood Lymphocytes. Radiology, 277(2): 406-412.
• Referans4 FDA, 2017, https://www.fda.gov/media/107506/download (erişim tarihi:02.02.2021).
• Referans5 Fiechter M, Stehli J, Fuchs T A, Dougoud S, Gaemperli O, Kaufmann P A, 2013. Impact of Cardiac Magnetic Resonance Imaging on Human Lymphocyte DNA Integrity. European Heart Journal, 34: 2340–2345.
• Referans6 Hill M A, 2018. Cardiac MR Imaging Genotoxicity. European Heart Journal, 39: 313–315.
• Referans7 Haller C, Hizoh I, 2004. The Cytotoxicity of Iodinated Radiocontrast Agents on Renal Cells In Vitro. Investigative Radiology, 39(3): 149-154.
• Referans8 Kulaksız S, Bau M, 2011. Anthropogenic Gadolinium as a Microcontaminant in Tap Water Used as Drinking Water in Urban Areas and Megacities. Applied Geochemistry, 26:1877–1885.
• Referans9 Kulaksız S, Bau M, 2013. Anthropogenic Dissolved and Colloid/Nanoparticle-Bound Samarium, Lanthanum and Gadolinium in The Rhine River and The İmpending Destruction of The Natural Rare Earth Element Distribution in Rivers. Earth and Planetary Science Letters, 362: 43–50.
• Referans10 Lialiaris TS, 2013. Sister Chromatid Exchange, https://www.sciencedirect.com/science/article/pii/B9780123749840013711 (erişim tarihi: 02.02.2021).
• Referans11 Morcos S K, 2008. Extracellular Gadolinium Contrast Agents: Differences in Stability. European Journal of Radiology, 66:175–179.
• Referans12 Moorhead P S, Nowell P C, Mellman W J, Battips D M, Hungerford D A, 1960. Chromosome Preparations of Leukocytes Cultured From Human Peripheral Blood. Experimental Cell Research, 20: 613–616.
• Referans13 OECDilibrary, Magnetic resonance imaging (MRI) exams, https://www.oecd-ilibrary.org/social-issues-migration-health/magnetic-resonance-imaging-mri-exams-total-2014-1_mri-exam-total-table-2014-1-en (erişim tarihi: 02.02.2021).
• Referans14 Parant M, Sohm B, Flaya J, Perrat E, Chuburu F, Cadiou C, Rosin C, Cossu-Leguille C, 2019. Impact of Gadolinium-Based Contrast Agents on The Growth of Fish Cells Lines. Ecotoxicology and Environmental Safety, 182: 1-7.
• Referans15 Perrat E, Parant M, Sebastien Py J, Rosin C, Leguille C C, 2017. Bioaccumulation of Gadolinium in Freshwater Bivalves. Environmental Science and Pollution Research, 24:12405–12415.
• Referans16 Perry P, Wolff S, 1974. New Giemsa Method For The Differential Staining of Sister Chromatids. Nature, 251: 156–158.
• Referans17 Rozenfeld M N, Podberesky D J, 2018. Gadolinium-Based Contrast Agents in Children. Pediatric Radiology, 48:1188–1196.
• Referans18 Simi S, Ballardina M, Casella M, De Marchi D, Hartwig V, Giovannetti G, Vanello N, Gabbriellini S, Landini L, Lombardi M, 2008. Is The Genotoxic Effect of Magnetic Resonance Negligible? Low Persistence of Micronucleus Frequency in Lymphocytes of İndividuals After Cardiac Scan. Mutation Research 645: 39–43.
• Referans19 Tucker J D, Preston R J, Chromosome Aberrations, Micronuclei, Aneuploidy, Sister Chromatid Exchanges, And Cancer Risk Assessment. Mutation Research, 365: 147–159.
• Referans20 Wilson D M, Thompson L H, 2007. Molecular Mechanisms of Sister chromatid Exchange. Mutation Research, 616: 11–23.
• Referans21 Xia Q, Feng X, Huang H, Du L, Yang X, 2011. Gadolinium‐Induced Oxidative Stress Triggers Endoplasmic Reticulum Stress in Rat Cortical Neurons. Journal of Neurochemıstry, 117: 38-47.
• Referans22 Yildiz S, Cece H, Kaya I, Celik H, Taskin A, Aksoy N, Kocyigit A, Eren M A, 2011. Clinical Biochemistry, 44: 975–979.
• Referans23 Zhang H, Holt C M, Malık N, Shepherd L, Morcos K, 2000. Effects of Radiographic Contrast Media on Proliferation And Apoptosis of Human Vascular Endothelial Cells. The British Journal of Radiology, 73:1034-1041.