Abstract
Radioiodine (131I) is widely used in the treatment of hyperthyroidism and as an effective ablative therapy for differentiated thyroid cancer. Radioiodine (131I) constitutes 90% of the currently used therapies in the field of nuclear medicine. Here, we report the cytogenetic findings of a long-term follow-up study of 27 years on a male patient who received two rounds of radioiodine treatment within a span of 26 months between 1992 and 1994 for his papillary thyroid cancer. A comprehensive cytogenetic follow-up study utilizing cytokinesis blocked micronucleus assay, dicentric chromosome assay, genome wide translocations and inversions was initiated on this patient since the first administration of radioiodine in 1992. Frequencies of micronuclei (0.006/cell) and dicentric chromosomes (0.008/cell) detected in the current study were grossly similar to that reported earlier in 2019. The mFISH analysis detected chromosome aberrations in 8.6% of the cells in the form of both unbalanced and balanced translocations. Additionally, a clonal translocation involving chromosomes 14p; 15q was observed in 2 of the 500 cells analyzed. Out of the 500 cells examined, one cell showed a complex translocation (involving chromosomes 9, 10, and 16) besides 5 other chromosome rearrangements. Collectively, our study indicates that the past radioiodine exposure results in long-lasting chromosome damage and that the persistence of translocations can be useful for both retrospective biodosimetry and for monitoring chromosome instability in the lymphocytes of radioiodine exposed individuals.
References
1.
Ardito G, Lamberti L, Bigatti P, Cottino F. Comparison of chromosome aberration frequency before and after administration of 131I in two groups of thyroid cancer patients. Tumori. 1987;73(3):257–62.
2.
Brill AB, Stabin M, Bouville A, Ron E. Normal organ radiation dosimetry and associated uncertainties in nuclear medicine, with emphasis on iodine-131. Radiat Res. 2006;166(1 Pt 2):128–40.
3.
Cantolino SJ, Schmickel RD, Ball M, Cisar CF. Persistent chromosomal aberrations following radioiodine therapy for thyrotoxicosis. N Engl J Med. 1966;275(14):739–45.
4.
da Silva MA, Valgode FG, Gonzalez JA, Yoriyaz H, Guimaraes MI, Ribela MT, et al. Cytogenetic and dosimetric effects of (131)I in patients with differentiated thyroid carcinoma: comparison between stimulation with rhTSH and thyroid hormone withdrawal treatments. Radiat Environ Biophys. 2016;55(3):317–28.
5.
Frigo A, Dardano A, Danese E, Davi MV, Moghetti P, Colato C, et al. Chromosome translocation frequency after radioiodine thyroid remnant ablation: a comparison between recombinant human thyrotropin stimulation and prolonged levothyroxine withdrawal. J Clin Endocrinol Metab. 2009;94(9):3472–6.
6.
Hengstler JG, Bockisch A, Fuchs J, Grimm W, Zapf AO, Lade K, et al. Increase in DNA single-strand break rejoining by continuous exposure of human mononuclear blood cells to radioiodine ((131)I) in vitro. Int J Radiat Biol. 1997;72(5):607–13.
7.
Hershman JM, Okunyan A, Rivina Y, Cannon S, Hogen V, Hengstler JG, et al. Prevention of DNA double-strand breaks induced by radioiodide-(131)I in FRTL-5 thyroid cells. Endocrinology. 2011;152(3):1130–5.
8.
IAEA. Cytogenetic dosimetry: applications in preparedness for and response to radiation emergencies; 2011. p. 1–229.
9.
Iarmarcovai G, Ceppi M, Botta A, Orsiere T, Bonassi S. Micronuclei frequency in peripheral blood lymphocytes of cancer patients: a meta-analysis. Mutat Res. 2008;659(3):274–83.
10.
Joseph LJ, Bhartiya US, Raut YS, Kand P, Hawaldar RW, Nair N. Micronuclei frequency in peripheral blood lymphocytes of thyroid cancer patients after radioiodine therapy and its relationship with metastasis. Mutat Res. 2009;675(1-2):35–40.
11.
Khvostunov IK, Saenko VA, Krylov V, Rodichev A, Yamashita S. Cytogenetic biodosimetry and dose-rate effect after radioiodine therapy for thyroid cancer. Radiat Environ Biophys. 2017;56(3):213–26.
12.
Kusunoki Y, Kodama Y, Hirai Y, Kyoizumi S, Nakamura N, Akiyama M. Cytogenetic and immunologic identification of clonal expansion of stem cells into T and B lymphocytes in one Atomic-bomb survivor. Blood. 1995;86(6):2106–12.
13.
Lassmann M, Hanscheid H, Gassen D, Biko J, Meineke V, Reiners C, et al. In vivo formation of gamma-H2AX and 53BP1 DNA repair foci in blood cells after radioiodine therapy of differentiated thyroid cancer. J Nucl Med. 2010;51(8):1318–25.
14.
Lassmann M, Luster M, Hanscheid H, Reiners C. Blood dosimetry and dose-rate effects after radioiodine therapy of differentiated thyroid cancer. J Nucl Med. 2005;46(5):899.
15.
Lehmann L, Zitzelsberger H, Kellerer AM, Braselmann H, Kulka U, Georgiadou-Schumacher V, et al. Chromosome translocations in thyroid tissues from Belarussian children exposed to radioiodine from the Chernobyl accident, measured by FISH-painting. Int J Radiat Biol. 1996;70(5):513–6.
16.
Livingston GK, Escalona M, Foster A, Balajee AS. Persistent in vivo cytogenetic effects of radioiodine therapy: a 21-year follow-up study using multicolor FISH. J Radiat Res. 2018;59(1):10–7.
17.
Livingston GK, Foster AE, Elson HR. Effect of in vivo exposure to iodine-131 on the frequency and persistence of micronuclei in human lymphocytes. J Toxicol Environ Health. 1993;40(2–3):367–75.
18.
Livingston GK, Khvostunov IK, Gregoire E, Barquinero JF, Shi L, Tashiro S. Cytogenetic effects of radioiodine therapy: a 20-year follow-up study. Radiat Environ Biophys. 2016;55(2):203–13.
19.
Livingston GK, Ryan TL, Smith TL, Escalona MB, Foster AE, Balajee AS. Detection of simple, complex, and clonal chromosome translocations induced by internal radioiodine exposure: a cytogenetic follow-up case study after 25 years. Cytogenet Genome Res. 2019;159(4):169–81.
20.
Llloyd DC, Purrott RJ, Dolphin GW, Horton PW, Halnan KE, Scott JS, et al. A comparison of physical and cytogenetic estimates of radiation dose in patients treated with iodine-131 for thyroid carcinoma. Int J Radiat Biol Relat Stud Phys Chem Med. 1976;30(5):473–85.
21.
M’Kacher R, Legal JD, Schlumberger M, Aubert B, Beron-Gaillard N, Gaussen A, et al. Sequential biological dosimetry after a single treatment with iodine-131 for differentiated thyroid carcinoma. J Nucl Med. 1997;38(3):377–80.
22.
M’Kacher R, Legal JD, Schlumberger M, Voisin P, Aubert B, Gaillard N, et al. Biological dosimetry in patients treated with iodine-131 for differentiated thyroid carcinoma. J Nucl Med. 1996;37(11):1860–4.
23.
M’Kacher R, Schlumberger M, Legal JD, Violot D, Beron-Gaillard N, Gaussen A, et al. Biologic dosimetry in thyroid cancer patients after repeated treatments with iodine-131. J Nucl Med. 1998;39(5):825–9.
24.
Nofal MM, Beierwaltes WH. Persistent chromosomal aberrations following radioiodine therapy. J Nucl Med. 1964;5:840–50.
25.
Popova L, Hadjidekova V, Hadjieva T, Agova S, Vasilev I. Cytokinesis-block micronucleus test in patients undergoing radioiodine therapy for differentiated thyroid carcinoma. Hell J Nucl Med. 2005;8(1):54–7.
26.
Ryan TL, Pantelias AG, Terzoudi GI, Pantelias GE, Balajee AS. Use of human lymphocyte G0 PCCs to detect intra- and inter-chromosomal aberrations for early radiation biodosimetry and retrospective assessment of radiation-induced effects. PLoS One. 2019;14(5):e0216081.
27.
Sanders M. Chromosomal aberrations following radioiodine therapy. Can Med Assoc J. 1967;96(15):1117–8.
28.
Serna A, Alcaraz M, Navarro JL, Acevedo C, Vicente V, Canteras M. Biological dosimetry and Bayesian analysis of chromosomal damage in thyroid cancer patients. Radiat Prot Dosimetry. 2008;129(4):372–80.
29.
Wuttke K, Streffer C, Muller WU, Reiners C, Biko J, Demidchik E. Micronuclei in lymphocytes of children from the vicinity of Chernobyl before and after 131I therapy for thyroid cancer. Int J Radiat Biol. 1996;69(2):259–68.
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