Araştırma Makalesi
BibTex RIS Kaynak Göster

Cytotoxicity and Genotoxicity Assessment of Gadoteric Acid in Breast Cancer Cells

Yıl 2025, Cilt: 52 Sayı: 3, 559 - 567, 16.09.2025
https://doi.org/10.5798/dicletip.1785119

Öz

Background: Gadoteric acid is utilized in magnetic resonance imaging (MRI) as a paramagnetic macrocyclic gadolinium-based contrast agent (GBCA) in breast cancer patients. However, in parallel with its diagnostic and prognostic use, the effect of gadoteric acid on MCF-7 cells has not yet been demonstrated. The aim of this study was to examine the cytogenotoxic effects of gadoteric acid on MCF-7 breast cancer cells.
Methods: MCF-7 cells were incubated with gadoteric acid (0.1-100 mM). The cytotoxic effect was examined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. The DNA damage effect of gadoteric acid on breast cancer cells by incubation at multiples of IC50 (1.84 mM, 3.67 mM, 7.35 mM, and 14.7 mM) was examined by Comet assay.
Results: Gadoteric acid (1-100 mM) significantly increased cytotoxicity in MCF-7 breast cancer cells (p < 0.001, p < 0.0001, and p < 0.0001, respectively). Gadoteric acid (1.84 mM, 3.67 mM, 7.35 mM, and 14.7 mM) dramatically increased genotoxicity in breast cancer cells (p < 0.01, p < 0.01, p < 0.01 and p < 0.01, respectively).
Conclusion: The results of our study indicate that gadoteric acid, which is used for diagnostic purposes in breast cancer, shows cytogenotoxic effect in MCF-7 cells under in vitro conditions. Our findings constitute the basic stepping stone for further studies in terms of therapeutic potential and additional studies are needed for clinical relevance.

Etik Beyan

We performed in vitro experiments with the commercially available MCF-7 breast cancer cell line. Since primary tissue samples, human participants and/or animal subjects were not used in our research process, ethical approval from any ethics committee is not required. MCF-7 cells were sourced from the American Type Culture Collection (ATCC, Shanghai, China).

Kaynakça

  • 1.Trayes KP, Cokenakes SEH. Breast CancerTreatment. Am Fam Physician. 2021;104:171-8.
  • 2.Burguin A, Diorio C, Durocher F. Breast cancertreatments: updates and new challenges. Journal ofpersonalized medicine 2021;11:808.
  • 3.Morelli MB, Bongiovanni C, Da Pra S, et al.Cardiotoxicity of anticancer drugs: molecularmechanisms and strategies for cardioprotection.Frontiers in cardiovascular medicine2022;9:847012.
  • 4.Fernández Y, Cueva J, Palomo AG, et al. Noveltherapeutic approaches to the treatment ofmetastatic breast cancer. Cancer Treat Rev.2010;36:33-42.
  • 5.Zhang W, Wang M, Lv W, et al. Long-TermTreatment with Gadopentetic Acid or GadodiamideIncreases TRPC5 Expression and DecreasesAdriamycin Nuclear Accumulation in Breast CancerCells. Cells. 2023;12.
  • 6.Seithe T, Braun J, Wolf M, et al. Diagnostic efficacyand safety of gadoteric acid MR mammography in1537 patients. Eur J Radiol. 2016;85:2281-7.
  • 7.Coimbra S, Rocha S, Sousa NR, et al. ToxicityMechanisms of Gadolinium and Gadolinium-BasedContrast Agents-A Review. Int J Mol Sci. 2024;25.
  • 8.Cowling T, Frey N. Macrocyclic and lineargadolinium based contrast agents for adultsundergoing magnetic resonance imaging: a reviewof safety. 2019.
  • 9.Robertson AG, Rendina LM. Gadoliniumtheranostics for the diagnosis and treatment ofcancer. Chemical Society Reviews. 2021;50:4231-44.
  • 10.Comşa Ş, Cîmpean AM, Raica M. The Story ofMCF-7 Breast Cancer Cell Line: 40 years ofExperience in Research. Anticancer Res.2015;35:3147-54.
  • 11.Senthilraja P, Kathiresan K. In vitro cytotoxicityMTT assay in Vero, HepG2 and MCF-7 cell lines study of Marine Yeast. Journal of applied pharmaceuticalscience. 2015;5:080-4.
  • 12.Thamizhiniyan V, Young-Woong C, Young-KyoonK.The cytotoxic nature of Acanthopanaxsessiliflorus stem bark extracts in human breastcancer cells. Saudi Journal of Biological Sciences.2015;22:752-9.
  • 13.Akbas E, Unal F, Yuzbasioglu D. Genotoxic effectsof gadobutrol and gadoversetamide activesubstances used in magnetic resonance imaging inhuman peripheral lymphocytes in vitro. Drug ChemToxicol. 2022;45:2471-82.
  • 14.Guerreiro PS, Fernandes AS, Costa JG, et al.Differential effects of methoxyamine on doxorubicincytotoxicity and genotoxicity in MDA-MB-231human breast cancer cells. Mutat Res Genet Toxicol Environ Mutagen. 2013;757:140-7.
  • 15.Adam M, Ozcan S, Dalkilic S, et al. Modulation ofNeuronal Damage in DRG by Asprosin in a High-Glucose Environment and Its Impact on miRNA181-a Expression in Diabetic DRG. NeurotoxicityResearch. 2024;42:5.
  • 16.Bower DV, Richter JK, von Tengg-Kobligk H,Heverhagen JT, Runge VM. Gadolinium-based MRIcontrast agents induce mitochondrial toxicity andcell death in human neurons, and toxicity increaseswith reduced kinetic stability of the agent.Investigative radiology. 2019;54:453-63.
  • 17.Mahmood F, Nielsen UG, Jørgensen CB, Brink C,Thomsen HS, Hansen RH. Safety of gadolinium basedcontrast agents in magnetic resonance imaging-guided radiotherapy–An investigation of chelatestability using relaxometry. Physics and imaging inradiation oncology. 2022;21:96-100.
  • 18.Singh NP, McCoy MT, Tice RR, Schneider EL. Asimple technique for quantitation of low levels ofDNA damage in individual cells. Experimental cellresearch. 1988;175:184-91.
  • 19.Bilgin B, Husunet M. Gadobutrol Exerts aCytogenotoxic Effect in SH‐SY5Y NeuroblastomaCells. European Journal of Therapeutics.2025;31:81-9.
  • 20.Do C, DeAguero J, Brearley A, et al. Gadolinium-Based Contrast Agent Use, Their Safety, and PracticeEvolution. Kidney360. 2020;1:561-8.
  • 21.Supawat B, Moungthong P, Chanloi C, et al.Effects of gadolinium-based magnetic resonanceimaging contrast media on red blood cells and K562cancer cells. J Trace Elem Med Biol.2020;62:126640.
  • 22.Zhang W, Wang M, Lv W, et al. Long-termtreatment with gadopentetic acid or gadodiamideincreases trpc5 expression and decreasesadriamycin nuclear accumulation in breast cancercells. Cells. 2023;12:1304.
  • 23.Friebe B, Godenschweger F, Fatahi M, et al. Thepotential toxic impact of different gadolinium-basedcontrast agents combined with 7-T MRI on isolatedhuman lymphocytes. Eur Radiol Exp. 2018;2:40.
  • 24.Cobanoglu H. Assessment of genetic damageinduced by gadolinium-based radiocontrast agents.J Trace Elem Med Biol. 2022;70:126914.
  • 25.Lajous H, Riva R, Lelièvre B, et al. HybridGd(3+)/cisplatin cross-linked polymer nanoparticlesenhance platinum accumulation and formation ofDNA adducts in glioblastoma cell lines. Biomater Sci.2018;6:2386-409.
  • 26.Maughan KL, Lutterbie MA, Ham PS. Treatmentof breast cancer. American family physician.2010;81:1339-46.
  • 27.Wang D, Xu Z, Yu H, et al. Treatment of metastaticbreast cancer by combination of chemotherapy andphotothermal ablation using doxorubicin-loadedDNA wrapped gold nanorods. Biomaterials.2014;35:8374-84.
  • 28.Alsamri H, Al Dhaheri Y, Iratni R. TargetingTriple-Negative Breast Cancer by the Phytopolyphenol Carnosol: ROS-Dependent Mechanisms. Antioxidants (Basel). 2023;12.
  • 29.Solmaz V, Köse Özlece H, Fatih Bozkurt M, ÖzkulB, Erbaş O. Repeated gadoteric acid and gadobutrolexposure causes deterioration of behavior andmemory functions in rats: MRI, histopathologicaland biochemical evidence. Brain Res.2021;1754:147256.
  • 30.Akbas E, Unal F, Yuzbasioglu D. Cellular toxicitiesof gadolinium‐based contrast agents used inmagnetic resonance imaging. Journal of AppliedToxicology. 2023;43:958-72.

Gadoterı̇k Ası̇dı̇n Meme Kanserı̇ Hücrelerı̇nde Sı̇totoksı̇sı̇te ve Genotoksı̇sı̇te Değerlendı̇rmesı̇

Yıl 2025, Cilt: 52 Sayı: 3, 559 - 567, 16.09.2025
https://doi.org/10.5798/dicletip.1785119

Öz

Giriş: Gadoterik asit, meme kanseri hastalarında paramanyetik makrosiklik gadolinyum bazlı kontrast madde (GBKA) olarak manyetik rezonans görüntülemede (MRG) kullanılmaktadır. Ancak, tanısal ve prognostik kullanımına paralel olarak, gadoterik asidin MCF-7 hücreleri üzerindeki etkisi henüz gösterilmemiştir. Bu çalışmanın amacı, gadoterik asidin MCF-7 meme kanseri hücreleri üzerindeki sitogenotoksik etkilerini incelemektir.
Yöntemler: MCF-7 hücreleri gadoterik asit (0.1-100 mM) ile inkübe edilmiştir. Sitotoksik etki 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) testi ile incelenmiştir. Gadoterik asidin meme kanseri hücreleri üzerindeki DNA hasarı etkisi IC50'nin katlarında (1.84 mM, 3.67 mM, 7.35 mM ve 14.7 mM) inkübasyon ile Comet testi ile incelenmiştir.
Bulgular: Gadoterik asit (1-100 mM) MCF-7 meme kanseri hücrelerinde sitotoksisiteyi önemli ölçüde artırmıştır (sırasıyla p < 0.001, p < 0.0001 ve p < 0.0001). Gadoterik asit (1.84 mM, 3.67 mM, 7.35 mM ve 14.7 mM) meme kanseri hücrelerinde genotoksisiteyi önemli ölçüde artırmıştır (sırasıyla p < 0.01, p < 0.01, p < 0.01 ve p < 0.01).
Sonuç: Çalışmamızın sonuçları, meme kanserinde tanı amaçlı kullanılan gadoterik asidin in vitro koşullarda MCF-7 hücrelerinde sitogenotoksik etki gösterdiğini ortaya koymaktadır. Bulgularımız terapötik potansiyel açısından ileri çalışmalar için temel basamak teşkil etmekte olup klinik uygunluk için ek çalışmalara ihtiyaç duyulmaktadır.

Kaynakça

  • 1.Trayes KP, Cokenakes SEH. Breast CancerTreatment. Am Fam Physician. 2021;104:171-8.
  • 2.Burguin A, Diorio C, Durocher F. Breast cancertreatments: updates and new challenges. Journal ofpersonalized medicine 2021;11:808.
  • 3.Morelli MB, Bongiovanni C, Da Pra S, et al.Cardiotoxicity of anticancer drugs: molecularmechanisms and strategies for cardioprotection.Frontiers in cardiovascular medicine2022;9:847012.
  • 4.Fernández Y, Cueva J, Palomo AG, et al. Noveltherapeutic approaches to the treatment ofmetastatic breast cancer. Cancer Treat Rev.2010;36:33-42.
  • 5.Zhang W, Wang M, Lv W, et al. Long-TermTreatment with Gadopentetic Acid or GadodiamideIncreases TRPC5 Expression and DecreasesAdriamycin Nuclear Accumulation in Breast CancerCells. Cells. 2023;12.
  • 6.Seithe T, Braun J, Wolf M, et al. Diagnostic efficacyand safety of gadoteric acid MR mammography in1537 patients. Eur J Radiol. 2016;85:2281-7.
  • 7.Coimbra S, Rocha S, Sousa NR, et al. ToxicityMechanisms of Gadolinium and Gadolinium-BasedContrast Agents-A Review. Int J Mol Sci. 2024;25.
  • 8.Cowling T, Frey N. Macrocyclic and lineargadolinium based contrast agents for adultsundergoing magnetic resonance imaging: a reviewof safety. 2019.
  • 9.Robertson AG, Rendina LM. Gadoliniumtheranostics for the diagnosis and treatment ofcancer. Chemical Society Reviews. 2021;50:4231-44.
  • 10.Comşa Ş, Cîmpean AM, Raica M. The Story ofMCF-7 Breast Cancer Cell Line: 40 years ofExperience in Research. Anticancer Res.2015;35:3147-54.
  • 11.Senthilraja P, Kathiresan K. In vitro cytotoxicityMTT assay in Vero, HepG2 and MCF-7 cell lines study of Marine Yeast. Journal of applied pharmaceuticalscience. 2015;5:080-4.
  • 12.Thamizhiniyan V, Young-Woong C, Young-KyoonK.The cytotoxic nature of Acanthopanaxsessiliflorus stem bark extracts in human breastcancer cells. Saudi Journal of Biological Sciences.2015;22:752-9.
  • 13.Akbas E, Unal F, Yuzbasioglu D. Genotoxic effectsof gadobutrol and gadoversetamide activesubstances used in magnetic resonance imaging inhuman peripheral lymphocytes in vitro. Drug ChemToxicol. 2022;45:2471-82.
  • 14.Guerreiro PS, Fernandes AS, Costa JG, et al.Differential effects of methoxyamine on doxorubicincytotoxicity and genotoxicity in MDA-MB-231human breast cancer cells. Mutat Res Genet Toxicol Environ Mutagen. 2013;757:140-7.
  • 15.Adam M, Ozcan S, Dalkilic S, et al. Modulation ofNeuronal Damage in DRG by Asprosin in a High-Glucose Environment and Its Impact on miRNA181-a Expression in Diabetic DRG. NeurotoxicityResearch. 2024;42:5.
  • 16.Bower DV, Richter JK, von Tengg-Kobligk H,Heverhagen JT, Runge VM. Gadolinium-based MRIcontrast agents induce mitochondrial toxicity andcell death in human neurons, and toxicity increaseswith reduced kinetic stability of the agent.Investigative radiology. 2019;54:453-63.
  • 17.Mahmood F, Nielsen UG, Jørgensen CB, Brink C,Thomsen HS, Hansen RH. Safety of gadolinium basedcontrast agents in magnetic resonance imaging-guided radiotherapy–An investigation of chelatestability using relaxometry. Physics and imaging inradiation oncology. 2022;21:96-100.
  • 18.Singh NP, McCoy MT, Tice RR, Schneider EL. Asimple technique for quantitation of low levels ofDNA damage in individual cells. Experimental cellresearch. 1988;175:184-91.
  • 19.Bilgin B, Husunet M. Gadobutrol Exerts aCytogenotoxic Effect in SH‐SY5Y NeuroblastomaCells. European Journal of Therapeutics.2025;31:81-9.
  • 20.Do C, DeAguero J, Brearley A, et al. Gadolinium-Based Contrast Agent Use, Their Safety, and PracticeEvolution. Kidney360. 2020;1:561-8.
  • 21.Supawat B, Moungthong P, Chanloi C, et al.Effects of gadolinium-based magnetic resonanceimaging contrast media on red blood cells and K562cancer cells. J Trace Elem Med Biol.2020;62:126640.
  • 22.Zhang W, Wang M, Lv W, et al. Long-termtreatment with gadopentetic acid or gadodiamideincreases trpc5 expression and decreasesadriamycin nuclear accumulation in breast cancercells. Cells. 2023;12:1304.
  • 23.Friebe B, Godenschweger F, Fatahi M, et al. Thepotential toxic impact of different gadolinium-basedcontrast agents combined with 7-T MRI on isolatedhuman lymphocytes. Eur Radiol Exp. 2018;2:40.
  • 24.Cobanoglu H. Assessment of genetic damageinduced by gadolinium-based radiocontrast agents.J Trace Elem Med Biol. 2022;70:126914.
  • 25.Lajous H, Riva R, Lelièvre B, et al. HybridGd(3+)/cisplatin cross-linked polymer nanoparticlesenhance platinum accumulation and formation ofDNA adducts in glioblastoma cell lines. Biomater Sci.2018;6:2386-409.
  • 26.Maughan KL, Lutterbie MA, Ham PS. Treatmentof breast cancer. American family physician.2010;81:1339-46.
  • 27.Wang D, Xu Z, Yu H, et al. Treatment of metastaticbreast cancer by combination of chemotherapy andphotothermal ablation using doxorubicin-loadedDNA wrapped gold nanorods. Biomaterials.2014;35:8374-84.
  • 28.Alsamri H, Al Dhaheri Y, Iratni R. TargetingTriple-Negative Breast Cancer by the Phytopolyphenol Carnosol: ROS-Dependent Mechanisms. Antioxidants (Basel). 2023;12.
  • 29.Solmaz V, Köse Özlece H, Fatih Bozkurt M, ÖzkulB, Erbaş O. Repeated gadoteric acid and gadobutrolexposure causes deterioration of behavior andmemory functions in rats: MRI, histopathologicaland biochemical evidence. Brain Res.2021;1754:147256.
  • 30.Akbas E, Unal F, Yuzbasioglu D. Cellular toxicitiesof gadolinium‐based contrast agents used inmagnetic resonance imaging. Journal of AppliedToxicology. 2023;43:958-72.
Toplam 30 adet kaynakça vardır.

Ayrıntılar

Birincil Dil İngilizce
Konular Sağlık Kurumları Yönetimi, Tıp Eğitimi, Sağlık Hizmetleri ve Sistemleri (Diğer)
Bölüm Original Articles
Yazarlar

Batuhan Bilgin

Ibrahim Halil Kenger Bu kişi benim

Yayımlanma Tarihi 16 Eylül 2025
Gönderilme Tarihi 11 Temmuz 2025
Kabul Tarihi 4 Eylül 2025
Yayımlandığı Sayı Yıl 2025 Cilt: 52 Sayı: 3

Kaynak Göster

APA Bilgin, B., & Kenger, I. H. (2025). Cytotoxicity and Genotoxicity Assessment of Gadoteric Acid in Breast Cancer Cells. Dicle Medical Journal, 52(3), 559-567. https://doi.org/10.5798/dicletip.1785119
AMA Bilgin B, Kenger IH. Cytotoxicity and Genotoxicity Assessment of Gadoteric Acid in Breast Cancer Cells. diclemedj. Eylül 2025;52(3):559-567. doi:10.5798/dicletip.1785119
Chicago Bilgin, Batuhan, ve Ibrahim Halil Kenger. “Cytotoxicity and Genotoxicity Assessment of Gadoteric Acid in Breast Cancer Cells”. Dicle Medical Journal 52, sy. 3 (Eylül 2025): 559-67. https://doi.org/10.5798/dicletip.1785119.
EndNote Bilgin B, Kenger IH (01 Eylül 2025) Cytotoxicity and Genotoxicity Assessment of Gadoteric Acid in Breast Cancer Cells. Dicle Medical Journal 52 3 559–567.
IEEE B. Bilgin ve I. H. Kenger, “Cytotoxicity and Genotoxicity Assessment of Gadoteric Acid in Breast Cancer Cells”, diclemedj, c. 52, sy. 3, ss. 559–567, 2025, doi: 10.5798/dicletip.1785119.
ISNAD Bilgin, Batuhan - Kenger, Ibrahim Halil. “Cytotoxicity and Genotoxicity Assessment of Gadoteric Acid in Breast Cancer Cells”. Dicle Medical Journal 52/3 (Eylül2025), 559-567. https://doi.org/10.5798/dicletip.1785119.
JAMA Bilgin B, Kenger IH. Cytotoxicity and Genotoxicity Assessment of Gadoteric Acid in Breast Cancer Cells. diclemedj. 2025;52:559–567.
MLA Bilgin, Batuhan ve Ibrahim Halil Kenger. “Cytotoxicity and Genotoxicity Assessment of Gadoteric Acid in Breast Cancer Cells”. Dicle Medical Journal, c. 52, sy. 3, 2025, ss. 559-67, doi:10.5798/dicletip.1785119.
Vancouver Bilgin B, Kenger IH. Cytotoxicity and Genotoxicity Assessment of Gadoteric Acid in Breast Cancer Cells. diclemedj. 2025;52(3):559-67.