Formation of micronuclei and of clastogenic factor(s) in patients receiving therapeutic doses of iodine-131

The micronucleus (MN) assay in peripheral blood lymphocytes was applied to assess the genotoxic potential of a single dose of iodine-131 (I-131) given to six patients for ablation of thyroid remnants after total thyroidectomy. Lymphocytes were taken at various times after I-131 therapy (from 2 to 180 days), and evaluated for the presence of MN in the binucleated cells identified after blocking cytokynesis with cytochalasin B. The presence of ultrafiltered, low-molecular weight, clastogenic factor(s) (CFs) in the plasma of 11 patient undergoing I-131 therapy was also sequentially assessed. A significantly increased MN frequency was observed in lymphocytes of patients as soon as the first sampling time (2 days after I-131 therapy), multifactor analysis of variance (MANOVA): P < 0.0001, peaking at day 7 at almost four-fold the spontaneous frequency observed in the pre-therapy samples. MN frequency slowly declined thereafter, reaching the baseline levels at the 180-day time point. When tested against peripheral blood lymphocytes from a healthy donor, the ultrafiltered CFs obtained from 11 patient's plasma induced a significant increase of the MN frequency peaking at day 15. Thereafter, a slow MN frequency decline was observed and the baseline frequency was reached after 180 days. A significant relationship was found between the MN frequency observed in lymphocytes of patients after I-131 therapy and the genotoxic Us activity present in their plasma (P = 0.019). These findings suggest that I-131 induces a significant increase in the MN frequency of peripheral blood lymphocytes, as well as the formation of transferable Us which persist for at least 60 days after administration of the radionuclide. The presence of these Us might be responsible of chromosome aberrations often observed in cultured lymphocytes following X-ray exposure. The possibility of reducing the genotoxic activity of radionuclide therapy by chemoprevention of Us with antioxidant drugs remains to be explored. (C) 2002 Elsevier Science B.V. All rights reserved.