Effects of I-131 ablation/metastasis treatment on DNA damage parameters in patients with differentiated thyroid cancer: a pilot study

Yıl 2025, Cilt: 50 Sayı: 3, 609 - 616, 30.09.2025

Emine Kılıç Toprak , Tarık Şengöz , Olga Yaylalı , Özgen Kılıç Erkek , Yasin Özdemir , Burak Oymak , Hande Şenol , Z. Melek Küçükatay , Vural Küçükatay , Doğangün Yüksel

https://doi.org/10.17826/cumj.1589549

Öz

Purpose: The purpose of this study was to ascertain how radioactive iodine therapy (RAIT). affected the DNA damage in the lymphocytes of differentiated thyroid cancer (DTC) patients.
Materials and Methods: Our study included 21 DTC patients in total, with a mean age of 45.09±10.02 years. Six (28.6%) of the 21 patients had a low dose of RAIT (≤30 mCi), eleven (52.4%) received a moderate dose of ablation (31 to 100 mCi), and four (%19) received a high dose (>100 mCi). Before, one week, and six months following treatment, venous blood samples were obtained from each patient. DNA damage was evaluated using the COMET assay. For a quantitative analysis of DNA damage, a number of characteristics were assessed, including head length, tail length, head intensity, tail intensity, and tail moment.
Results: Compared to before treatment (23.83±9.82), tail intensity levels were considerably lower after treatment (1st week and 6th months) (18.30±6.48 vs. 18.06±5.58). Following therapy (1st week and 6th months), the head intensity values were statistically substantially higher (81.69±6.48 vs. 81.93±5.58) than they were prior to treatment (76.16±9.82). Six months after therapy, the tail moment was lower than it was before treatment (5.24±2.51 vs. 8.04±3.86).
Conclusion: Treatment has a beneficial effect on peripheral blood cells, as seen by the increase in head intensity and decrease in tail intensity and moment after treatment. By triggering repair mechanisms, RAIT may have activated protective effects on the DNA of lymphocytes.

Anahtar Kelimeler

Differentiated thyroid cancer , I-131 , radioactive iodine theraphy , DNA damage , COMET assay

Diferansiye tiroid kanseri olan hastalarda I-131 ablasyonu/metastaz tedavisinin DNA hasarı parametreleri üzerindeki etkileri: pilot çalışma

Öz

Amaç: Bu çalışmanın amacı, radyoaktif iyot tedavisinin (RAIT) farklılaşmış tiroid kanseri (DTC) hastalarının lenfositlerindeki DNA hasarını nasıl etkilediğini belirlemekti.
Gereç ve Yöntem: Çalışmamıza toplam 21 DTC hastası dahil edildi ve yaş ortalamaları 45.09±10.02 yıldı. 21 hastanın altısı (%28.6) düşük doz RAIT (≤30 mCi) aldı, on biri (%52.4) orta doz ablasyon (31 ila 100 mCi) aldı ve dördü (%19) yüksek doz (>100 mCi) aldı. Tedaviden önce, bir hafta ve altı ay sonra her hastadan venöz kan örnekleri alındı. DNA hasarı COMET testi kullanılarak değerlendirildi. DNA hasarının kantitatif analizi için baş uzunluğu, kuyruk uzunluğu, baş yoğunluğu, kuyruk yoğunluğu ve kuyruk momenti dahil olmak üzere çeşitli parametreler değerlendirildi.
Bulgular: Kuyruk yoğunluğu değerleri tedaviden sonra (1 hafta ve 6 ay) tedavi öncesine (23,83 ± 9,82) kıyasla önemli ölçüde daha düşüktü (18,30 ± 6,48'e karşı 18,06 ± 5,58). Baş yoğunluğu değerleri tedaviden sonra (1. hafta ve 6. ay) (81.69±6.48'e karşı 81.93±5.58) tedavi öncesine (76.16±9.82) göre istatistiksel olarak anlamlı derecede daha yüksekti. Kuyruk momenti tedaviden 6 ay sonra tedavi öncesine göre daha düşüktü (5.24±2.51'e karşı 8.04±3.86).
Sonuç: Tedaviden sonra baş yoğunluğunda artış ve kuyruk yoğunluğunda ve momentinde azalma, tedavinin periferik kan hücreleri üzerinde olumlu bir etkiye sahip olduğunu göstermiştir. RAIT'in onarım mekanizmalarını aktive ederek lenfosit DNA'sı üzerinde koruyucu etkileri aktive etmiş olabileceği düşünülebilir.

Anahtar Kelimeler

Farklılaşmış tiroid kanseri , I-131 , radyoaktif iyot tedavisi , DNA hasarı , COMET analizi

Kaynakça

• Laha D, Nilubol N, Boufraqech M. New therapies for advanced thyroid cancer. Front Endocrinol (Lausanne). 2020;11:82.
• Dralle H, Machens A, Basa J, Fatourechi V, Franceschi S, Hay ID et al. Follicular cell-derived thyroid cancer. Nat Rev Dis Primers. 2015;1:15077.
• Coca-Pelaz A, Shah JP, Hernandez-Prera JC, Ghossein RA, Rodrigo JP, Hartl DM et al. Papillary thyroid cancer-aggressive variants and impact on management: a narrative review. Adv Ther. 2020;37:3112-28.
• Christofer Juhlin C, Mete O, Baloch ZW. The 2022 WHO classification of thyroid tumors: novel concepts in nomenclature and grading. Endocr Relat Cancer. 2022;30:e220293.
• Haugen BR, Alexander EK, Bible KC, Doherty GM, Mandel SJ, Nikiforov YE et al. 2015 American thyroid association management guidelines for adult patients with thyroid nodules and differentiated thyroid cancer: the american thyroid association guidelines task force on thyroid nodules and differentiated thyroid cancer. Thyroid. 2016;26:1-133.
• Park KW, Wu JX, Du L, Leung AM, Yeh MW, Livhits MJ. Decreasing use of radioactive iodine for low-risk thyroid cancer in california, 1999 to 2015. J Clin Endocrinol Metab. 2018;103:1095-101.
• Signore A, Campagna G, Marinaccio J, Vitis M, Lauri C, Berardinelli F et al. Analysis of short-term and stable DNA damage in patients with differentiated thyroid cancer treated with 131i in hypothyroidism or with recombinant human thyroid-stimulating hormone for remnant ablation. J Nucl Med. 2022;63:1515-22.
• Zhang C, Xiang B. The underlying mechanisms and strategies of DNA damage and repair in radiation sialadenitis. Oral Dis. 2023;29:990-5.
• Palot Manzil FF, Kaur H. Radioactive Iodine for Thyroid Malignancies. [Updated 2024 Jul 26]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan. Available from: https://www.ncbi.nlm.nih.gov/books/NBK580567/.
• Cabanillas ME, McFadden DG, Durante C. Thyroid cancer. Lancet. 2016;388:2783-95.
• Carballo M, Quiros RM. To treat or not to treat: the role of adjuvant radioiodine therapy in thyroid cancer patients. J Oncol. 2012;2012:707156.
• Buscombe J. Controversies in the radioiodine treatment of patients with differentiated thyroid cancer. Semin Nucl Med. 2023;53:475-80.
• Bitgen N, Bayram F, Hamurcu Z, Baskol G, Ozturk F, Abdulrezzak U et al. The effects of iodine 131 treatment on chromosomal and oxidative DNA damage in papillary thyroid carcinoma. Mutat Res Genet Toxicol Environ Mutagen. 2024;898:503797.
• Molenaar RJ, Sidana S, Radivoyevitch T, Advani AS, Gerds AT, Carraway HE et al. Risk of hematologic malignancies after radioiodine treatment of well-differentiated thyroid cancer. J Clin Oncol. 2018;36:1831-9.
• Hosseinimehr SJ, Shafaghati N, Hedayati M. Genotoxicity induced by iodine-131 in human cultured lymphocytes. Interdiscip Toxicol. 2013;6:74-6.
• Doai M, Watanabe N, Takahashi T, Taniguchi M, Tonami H, Iwabuchi K et al. Sensitive immunodetection of radiotoxicity after iodine-131 therapy for thyroid cancer using γ-H2AX foci of DNA damage in lymphocytes. Ann Nucl Med. 2013;27:233-8.
• Unlü S, Ozdemir S, Sümer S, Sağlar E, Taştan S, Kir M. Investigation of DNA damage by the alkaline comet assay in 131I-treated thyroid cancer patients. Anal Quant Cytopathol Histpathol. 2013;35:36-40.
• Gutiérrez S, Carbonell E, Galofré P, Creus A, Marcos R. The alkaline single-cell gel electrophoresis (SCGE) assay applied to the analysis of radiation-induced DNA damage in thyroid cancer patients treated with 131I. Mutat Res. 1998;413:111-9.
• Nandhakumar S, Parasuraman S, Shanmugam MM et al. Evaluation of DNA damage using single-cell gel electrophoresis (Comet Assay). J Pharmacol Pharmacother. 2011;2:107-11.
• Speit G, Hartmann A. The comet assay: a sensitive genotoxicity test for the detection of DNA damage and repair. Methods Mol Biol. 2006;314:275-86.
• Visvardis EE, Tassiou AM, Piperakis SM. Study of DNA damage induction and repair capacity of fresh and cryopreserved lymphocytes exposed to H2O2 and gamma-irradiation with the alkaline comet assay. Mutat Res 1997;383:71-80.
• Singh NP, Stephens RE, Schneider EL. Modifications of alkaline microgel electrophoresis for sensitive detection of DNA damage. Int J Radiat Biol. 1994;66:23-8.
• Rothkamm K, Löbrich M. Misrepair of radiation-induced DNA double-strand breaks and its relevance for tumorigenesis and cancer treatment (review). Int J Oncol. 2002;21:433-40.
• Mahaney BL, Meek K, Lees-Miller SP. Repair of ionizing radiation-induced DNA double-strand breaks by non-homologous end-joining. Biochem J. 2009;417:639-50.
• Plappert UG, Stocker B, Fender H, Fliedner TM. Changes in the repair capacity of blood cells as a biomarker for chronic low-dose exposure to ionizing radiation. Environ Mol Mutagen. 1997;30:153-60.
• Grzesiuk W, Nieminuszczy J, Kruszewski M, Iwanienko T, Plazinska M, Bogdanska M et al. DNA damage and its repair in lymphocytes and thyroid nodule cells during radioiodine therapy in patients with hyperthyroidism. J Mol Endocrinol. 2006;37:527-32.
• Wurm R, Burnet NG, Duggal N, Yarnold JR, Peacock JH. Cellular radiosensitivity and DNA damage in primary human fibroblasts. Int J Radiat Oncol Biol Phys. 1994;30:625-33.