Raut Yogita S, Bhartiya Uma S, Kand Purushottam, Hawaldar Rohini W, Asopa Ramesh V, Joseph Lebana J, Rajan Mgr
Radiation Medicine Centre, Bhabha Atomic Research Centre, C/O Tata Memorial Hospital Annexe, Parel, Mumbai, India.
Radiation Medicine Centre, Bhabha Atomic Research Centre, C/O Tata Memorial Hospital Annexe, Parel, Mumbai, India ; P. D. Hinduja National Hospital and Medical Research Centre, Mahim, Mumbai, India.
Indian J Clin Biochem. 2016 Mar;31(1):99-103. doi: 10.1007/s12291-015-0501-5. Epub 2015 Apr 28.
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.
目的是研究高浓度甲状腺素(T4)对甲状腺疾病患者外周血淋巴细胞(PBL)的体内遗传毒性作用。通过在来自健康供体的全血样本中添加递增浓度的T4(0.125 - 1 μM)进行体外实验来比较该作用。采用胞质分裂阻滞微核(CBMN)试验方法评估PBL中的DNA损伤。该研究纳入了104例患者,分为对照组(n = 49)、甲状腺功能亢进组(n = 31)和甲状腺功能减退组(n = 24)。与甲状腺功能减退组和甲状腺功能正常组相比,甲状腺功能亢进患者的微核(MN)频率显著增加,从而提示甲状腺功能亢进时遗传毒性增加(p < 0.001)。在体外实验中,与较低T4浓度(0.125和0.25 μM)及基础水平相比,T4浓度为0.5 μM及以上时MN频率显著增加(p = 0.000)。结果表明,如体内和体外实验所示,正常浓度的T4不表现出遗传毒性作用。体外实验中,T4浓度在0.5 μM及以上时毒性增加。因此,应及时有效地处理急性T4过量,以避免体内高浓度T4可能产生的遗传毒性作用。