METHIMAZOLE INHIBITS FRTL5 THYROID-CELL PROLIFERATION BY INDUCING S-PHASE ARREST OF THE CELL-CYCLE
METHIMAZOLE INHIBITS FRTL5 THYROID-CELL PROLIFERATION BY INDUCING S-PHASE ARREST OF THE CELL-CYCLE
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DOI：
10.1210/en.133.5.2403
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发表时间：
1993-11-01
期刊：
影响因子：
4.8
通讯作者：
BOYAGES, SC
中科院分区：
文献类型：
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作者：
SMERDELY, P;PITSIAVAS, V;BOYAGES, SC
以前的研究，使用氚标记的胸苷摄取测定，表明甲巯咪唑（MMI）对甲状腺细胞增殖无或刺激作用。在检查FRTL 5甲状腺细胞的细胞周期动力学的同时，我们观察到MMI对甲状腺细胞增殖的抑制作用。为了进一步检查该观察结果，将处于对数期增殖的FRTL 5细胞暴露于含有6H或6H中的MMI的培养基。使用流式细胞术DNA分析每24小时检查细胞数量和细胞周期动力学，持续96小时。我们发现MMI在整个实验期间抑制细胞增殖（通过细胞数量评估）。细胞周期分析显示细胞持续阻滞于S期。同时，GOG 1和G2M期细胞比例下降，与S期细胞周期阻滞一致。单独来看，S期细胞比例高的发现表明刺激了细胞增殖，这与先前使用氚化胸苷摄取试验评估细胞增殖的研究结果一致。然而，没有伴随的细胞总数增加，使这一论点无效，并认为MMI对细胞周期的具体影响。这项研究表明，迄今未被认可的抑制作用的MMI对FRTL 5甲状腺细胞增殖的影响，在理解更广泛的影响MMI对甲状腺细胞的生理。此外，这项研究强调了使用氚化胸苷摄取措施作为促有丝分裂活性的唯一指标的危险。
Previous studies, using tritiated thymidine uptake assays, had indicated a nil or stimulatory effect of methimazole (MMI) on thyroid cell proliferation. Whilst examining cell cycle kinetics of FRTL5 thyrocytes, we observed an inhibitory effect of MMI on thyroid cell proliferation. To further examine this observation, FRTL5 cells whilst in log phase proliferation were exposed to media containing either 6H or MMI in 6H. Cell number and cell cycle kinetics were examined using flow cytometric DNA analysis every 24 hrs for 96 hrs. We found that MMI inhibited cell proliferation (as assessed by cell number) throughout the experimental period. Cell cycle analysis revealed a persistent arrest of cells in S phase. Concomitantly, there was a fall in the proportion of cells in both GOG1 and G2M phases, in keeping with cell cycle arrest in S phase. Taken in isolation, the finding of a high proportion of cells in S phase would suggest stimulation of cell proliferation, consistent with the findings of previous studies which used tritiated thymidine uptake assays to assess cell proliferation. However, the absence of a concomitant increase in total cell number renders this argument invalid and argues for a specific effect of MMI on the cell cycle. This study demonstrates a hitherto unrecognised inhibitory action of MMI on FRTL5 thyroid cell proliferation which has implications in understanding the broader effects of MMI on thyroid cell physiology. Additionally, this study highlights the dangers of using tritiated thymidine uptake measures as the sole indicator of mitogenic activity.