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

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. Conclusions: 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.