Effect of l-Thyroxine on Micronuclei Frequency in Peripheral Blood Lymphocytes in Clinical and Experimental Conditions

Abstract

The aim was to study the genotoxic effect of high concentration of thyroxine (T4) in vivo in peripheral blood lymphocytes (PBL) of the patients suffering from thyroid disorders. The effect was compared by performing in vitro experiments with addition of increasing concentration of T4 (0.125-1 µM) in whole blood samples from healthy donors. Cytokinesis-blocked micronuclei (CBMN) assay method was used to assess the DNA damage in the PBL. The study included 104 patients which were grouped as control (n = 49), hyperthyroid (n = 31) and hypothyroid (n = 24). A significant increase in micronuclei (MN) frequency was observed in hyperthyroid patients when compared with the hypothyroid and euthyroid group thereby suggesting increased genotoxicity in hyperthyroidism (p < 0.001). A significant increase in MN frequency was observed at T4 concentration of 0.5 µM and above when compared to lower T4 concentrations (0.125 and 0.25 µM) and basal in in vitro experiments (p = 0.000). The results indicate that the T4 in normal concentration does not exhibit the genotoxic effect, as observed in both the in vivo and in vitro experiments. The toxicity of T4 increases at and above 0.5 μM concentration in vitro. Therefore acute T4 overdose should be handled promptly and effectively so as to avoid the possible genotoxic effect of high concentration of T4 in vivo.

Keywords: Genotoxicity; Hyperthyroid; Hypothyroid; Micronuclei; Thyroxine.

Fig. 1

Micronuclei frequency in peripheral blood lymphocytes of total study population. *p < 0.001 versus euthyroid, hypothyroid