Analysis of short term and stable DNA damage in patients with differentiated thyroid cancer treated with ¹³¹I in hypothyroidism or with rhTSH for remnant ablation

Abstract

It is well known that ionizing radiations 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 (1850 MBq), is associated with DNA damage by evaluating Comet assay, micronuclei and chromosome aberrations with multicolor fluorescent in situ hybridization (M-FISH). Methods: we studied 62 patients prepared with rhTSH or by thyroid hormone withdrawal (THW). In both groups we analyzed stable and unstable genetic alterations before ¹³¹I therapy and 1 week and 3 months 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 anti-oxidative stress. Results: we found comparable amount of DNA breaks evaluated by Comet assay and micronuclei test in both groups of patients at different time points, but a significant increase of stable chromosome aberrations evaluated by M-FISH (breaks and translocations) in patients prepared with THW. 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 anti-oxidants was found in all patients at any time point. In particular, patients prepared with THW, at 3 months, had significantly higher levels of free oxygen radicals than those prepared with rhTSH. Conclusion: an increase of stable chromosome aberrations respect to baseline is detectable after administration of low doses of ¹³¹I in patients prepared with THW but not in patients prepared with rhTSH. The clinical significance of these chromosomal alterations remains to be determined.