Mutation Research 514 (2002) 77–85 Formation of micronuclei and of clastogenic factor(s) in patients receiving therapeutic doses of iodine-131 Michela Ballardin a , Federica Gemignani a , Lisa Bodei b , Giuliano Mariani c , Marco Ferdeghini d , Anna Maria Rossi a , Lucia Migliore a , Roberto Barale a,∗ a Dipartimento di Scienze dell’Uomo e dell’Ambiente, University of Pisa, Pisa, Italy b Divisione di Medicina Nucleare, Istituto Europeo di Oncologia, University of Milano, Milano, Italy c Dipartimento di Medicina Interna, Università di Genova, Genova, Italy d Nuclear Medicine, Section of Radiology, Department of Biomedical-Morphologic Sciences, University of Verona, Verona, Italy Received 12 July 2001; received in revised form 13 September 2001; accepted 11 October 2001 Abstract The micronucleus (MN) assay in peripheral blood lymphocytes was applied to assess the genotoxic potential of a single dose of iodine-131 ( 131 I) given to six patients for ablation of thyroid remnants after total thyroidectomy. Lymphocytes were taken at various times after 131 I 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 131 I 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 131 I 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 131 I therapy and the genotoxic CFs activity present in their plasma (P = 0.019). These findings suggest that 131 I induces a significant increase in the MN frequency of peripheral blood lymphocytes, as well as the formation of transferable CFs which persist for at least 60 days after administration of the radionuclide. The presence of these CFs 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 CFs with antioxidant drugs remains to be explored. © 2002 Elsevier Science B.V. All rights reserved. Keywords: Differentiated thyroid cancer; Iodine-131 therapy; Genotoxicity; Micronuclei; Clastogenic factor(s) ∗ Corresponding author. Present address: Dipartimento di Scienze dell’Uomo e dell’Ambiente, Universit` a di Pisa, Via S. Giuseppe 22, 56100 Pisa, Italy. Tel.: +39-50-836224; fax: +39-50-551290. E-mail address: r.barale@geog.unipi.it (R. Barale). 1. Introduction Ablation of any thyroid remnants with iodine-131 ( 131 I) is the mainstay of the post-surgical management of patients with differentiated thyroid cancer deriving from the follicular epithelium (DTC) [1–6]. Even after 1383-5718/02/$ – see front matter © 2002 Elsevier Science B.V. All rights reserved. PII:S1383-5718(01)00323-0