Radioactive iodine-131 induces human thyrocyte cell line HTori 3 cell apoptosis and G2/M arrest in a p53-independent pathway

Objectives To investigate the cytotoxic effect of radioactive iodine-131 on the HTori 3 cell line and the mechanism of iodine-131-induced cell apoptosis in the thyrocyte cell.

Methods The HTori 3 cell line was used. Cell viability was quantitated by methyl-thiazolyl-tetrazolium assay (MTT), and cell apoptosis and cell cycle arrest were determined by flow cytometry. Quantitative real-time PCR and Western Blot assay were performed to determine the changes of expressions of p53, Bcl-2, Fas and GADD45 after radioactive iodine-131 irradiation

Results Iodine-131could inhibit HTori 3 cell growth via cell apoptosis and G2/M arrest in a time- and dose-dependent manner. The IC 50 (the concentration requird for 50% growth inhibition) of radioactive iodine-131 towards HTori 3 cell viability at 48 hrs was 27.75±2.22 MBq/ml. Up-regulation of Fas and suppression of Bcl-2 were observed after radioactive iodine-131 treatment. Quantitative real-time PCR showed an increase of GADD45 mRNA expression after HTori 3 cell being exposed to radioactive iodine-131. Strikingly, p53 mRNA as well as protein expression were not altered after radioactive iodine-131 exposure.

Conclusions We demonstrated that radioactive iodine-131could induce apoptosis in HTori 3 cells by down-regulating the expression of Bcl-2 and up-regulating Fas, and could up-regulate GADD45 mRNA expression to arrest HTori 3 at G2/M in a p53-independent pathway.