Methimazole inhibits FRTL5 thyroid cell proliferation by inducing S-phase arrest of the cell cycle.

Abstract

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 G0G1 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.