Abstract
It is well known that ionizing radiation can induce genetic damage and that oxidative stress is a major factor inducing it. Our aim was to investigate whether thyroid remnant ablation with low activities of 131I (1,850 MBq) is associated with DNA damage by evaluating the CometAssay, micronuclei, and chromosome aberrations with multicolor fluorescent in situ hybridization. Methods: We studied 62 patients prepared with recombinant human thyroid-stimulating hormone (rhTSH) or by thyroid hormone withdrawal. In both groups, we analyzed stable and unstable genetic alterations before 131I therapy and 1 wk and 3 mo after 131I administration. We also correlated the genetic damage with several variables, including the degree of radiation-induced oxidative stress, genetic polymorphisms of enzymes involved in DNA repair, and antioxidative stress. Results: We found a comparable amount of DNA breaks evaluated by CometAssay and micronuclei testing in both groups of patients at different time points, but there was a significant increase in stable chromosome aberrations evaluated by multicolor fluorescent in situ hybridization (breaks and translocations) in patients prepared with thyroid hormone withdrawal. Overall, high chromosome damage was associated with higher retained body radioactivity and unfavorable gene polymorphism. A high level of free oxygen radicals and a low level of antioxidants were found in all patients at any time point. In particular, patients prepared with thyroid hormone withdrawal, at 3 mo, had significantly higher levels of free oxygen radicals than those prepared with rhTSH. Conclusion: An increase in stable chromosome aberrations with respect to baseline is detectable after administration of low doses of 131I in patients prepared with thyroid hormone withdrawal but not in patients prepared with rhTSH. The clinical significance of these chromosomal alterations remains to be determined.
Highlights
Iodine-131 (131I) is used in clinical practice for thyroid remnant ablation in patients who undergo thyroidectomy for differentiated thyroid carcinoma (DTC)
Most patients were dismissed at day 2 but, 4 patients from HYPO group were dismissed at day 3 and 11 patients from rhTSH group were dismissed at day 1, confirming the lower residual body activity of patients treated with rhTSH as compared to patients in hypothyroidism
The calculated area under the curve (AUC) for the exposure rate through 120 h was 27% lower in rhTSH patients than in HYPO patients, reflecting lower residual body activity
Summary
Iodine-131 (131I) is used in clinical practice for thyroid remnant ablation in patients who undergo thyroidectomy for differentiated thyroid carcinoma (DTC). Several reports have shown chromosomal damage induced by 131I, only chromosomes 1, 2, 4, 8 and 10 have been analyzed [8,9,10,11,12] Despite this is a very controversial issue [3,5,13,14,15,16,17,18,19], a significant reduction of ablative treatments has been observed in the last decade. Secondary aims were: i) to analyze the level of baseline (i.e., pre- remnant ablation) genetic damage and oxidative stress in patients with DTC; ii) to evaluate the role of different DNA-repair and anti-oxidative genes in the occurrence of genetic damage and oxidative stress by analyzing genetic polymorphisms in patients. Secondary aims were: i) to analyze the level of baseline (i.e., pre- remnant ablation) genetic damage and oxidative stress in patients with DTC; ii) to evaluate the role of different DNA-repair and anti-oxidative genes in the occurrence of genetic damage and oxidative stress by analyzing genetic polymorphisms in patients. iii) to evaluate whether the yield of damage is comparable in patients prepared with rhTSH or by hypothyroidism
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