Investigation of Gadobutrol Genotoxicity in Human Peripheral Lymphocytes by Micronucleus Test


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Akbaş E., Ünal F., Yüzbaşıoğlu D.

9th International Academic Studies Conference (UBCAK 2022), Ankara, Turkey, 03 August 2022, pp.109-110

  • Publication Type: Conference Paper / Summary Text
  • City: Ankara
  • Country: Turkey
  • Page Numbers: pp.109-110
  • Gazi University Affiliated: Yes

Abstract

Magnetic resonance imaging (MRI) is a consolidated imaging technique for the multiparametric evaluation of tissues in various diseases. Despite the high resolution capability, in almost half of all the MRI examinations, the image contrast is insufficient, resulting in the use of contrast agents. Gadolinium-based contrast agents (GBCAs) are widely used to increase the accuracy of the diagnosis, one of the most preferred among them is gadobutrol, is administered for MRI of the central nervous system, kidneys, liver, and contrast increment in magnetic resonance angiography. Its use has also raised concerns about whether it has adverse effects on people's health. Therefore, in this study, the genotoxic effects of gadobutrol were assessed by Micronucleus Test in human peripheral lymphocytes in vitro. For this purpose, depending on both the LD50  value of gadobutrol in rodents and the recommended dose of use in humans, five concentrations (7,000, 14,000, 28,000, 56,000, and 112,000 μg/mL) of gadobutrol were applied to lymphocytes obtained from three healthy donors. A negative (distilled water) and a positive (Mitomycin C, 0.20 μg/mL) control were also used. In analyzes performed by examining binuclear cells, it was observed that gadobutrol forms binucleates with 1 micronucleus in human lymphocytes. It was determined that this contrast agent caused increases in MN frequency compared to the negative control, but these increases were not at a significant level. On the other hand, gadobutrol caused a decrease in the Nuclear Division Index (NDI) compared to the negative control, but these reductions were not statistically significant. These results indicate that gadobutrol did not have strong clastogenic and/or aneugenic effects in the MN test in human lymphocytes. However, further in vitro and in vivo genotoxicity tests should be carried out to reduce health concerns.