Genotoxic effects of gadobutrol and gadoversetamide active substances used in magnetic resonance imaging in human peripheral lymphocytes <i>in vitro</i>

Akbaş E., Ünal F., Yüzbaşıoğlu D.

DRUG AND CHEMICAL TOXICOLOGY, cilt.45, sa.6, ss.2471-2482, 2022 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 45 Sayı: 6
  • Basım Tarihi: 2022
  • Doi Numarası: 10.1080/01480545.2021.1957913
  • Dergi Adı: DRUG AND CHEMICAL TOXICOLOGY
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, BIOSIS, CAB Abstracts, Chemical Abstracts Core, EMBASE, Environment Index, Food Science & Technology Abstracts, International Pharmaceutical Abstracts, MEDLINE, Veterinary Science Database
  • Sayfa Sayıları: ss.2471-2482
  • Anahtar Kelimeler: Magnetic resonance imaging, gadolinium-based contrast agents, chromosome aberration, sister chromatid exchange, micronucleus, comet assay, SISTER-CHROMATID EXCHANGE, CONTRAST AGENTS, DNA-DAMAGE, MOLECULAR-MECHANISMS, SAFETY EVALUATION, GADOLINIUM, MICRONUCLEUS, DTPA, FREQUENCY, EXPOSURE
  • Gazi Üniversitesi Adresli: Evet

Özet

Gadobutrol and gadoversetamide are gadolinium-based contrast agents (GBCAs) widely used during magnetic resonance imaging examination. In this study, the genotoxicity of two GBCAs, gadobutrol and gadoversetamide, was investigated by using different endpoints: chromosome aberration (CAs), sister chromatid exchange (SCEs), and micronucleus (MNi). Human peripheral lymphocytes (PBLs) were treated with five concentrations (7 000, 14 000, 28 000, 56 000, and 112 000 mu g/mL) of both agents. While a few concentrations of gadobutrol significantly increased abnormal cell frequency and CA/Cell, nearly all the concentrations of gadoversetamide significantly elevated the same aberrations. Similarly, the effect of gadoversetamide on the formation of SCEs was higher than those of gadobutrol. Only one concentration of gadoversetamide significantly increased MN% but no gadobutrol. The comet assay was applied for the only gadobutrol which induced a significant increase in tail intensity at the highest concentration only. On the other hand, significantly decreased mitotic index (MI) was observed following both substances, again gadoversetamide was slightly higher than those of the gadobutrol. The results revealed that both the contrast agents are likely to induce genotoxic risk in PBLs. However, different concentrations and treatment periods should be examined in vitro and specifically in vivo with different test systems for the safer usage of these contrast agents.