Division of Endocrinology, Erasme Hospital, Université Libre de Bruxelles (ULB), Brussels, Belgium.
Institut de Recherche Interdisciplinaire en Biologie Humaine et Moleculaire (IRIBHM), School of Medicine, ULB, Brussels, Belgium.
J Clin Endocrinol Metab. 2020 Mar 1;105(3). doi: 10.1210/clinem/dgz185.
The early molecular events in human thyrocytes after 131I exposure have not yet been unravelled. Therefore, we investigated the role of TSH in the 131I-induced DNA damage response and gene expression in primary cultured human thyrocytes.
Following exposure of thyrocytes, in the presence or absence of TSH, to 131I (β radiation), γ radiation (3 Gy), and hydrogen peroxide (H2O2), we assessed DNA damage, proliferation, and cell-cycle status. We conducted RNA sequencing to profile gene expression after each type of exposure and evaluated the influence of TSH on each transcriptomic response.
Overall, the thyrocyte responses following exposure to β or γ radiation and to H2O2 were similar. However, TSH increased 131I-induced DNA damage, an effect partially diminished after iodide uptake inhibition. Specifically, TSH increased the number of DNA double-strand breaks in nonexposed thyrocytes and thus predisposed them to greater damage following 131I exposure. This effect most likely occurred via Gα q cascade and a rise in intracellular reactive oxygen species (ROS) levels. β and γ radiation prolonged thyroid cell-cycle arrest to a similar extent without sign of apoptosis. The gene expression profiles of thyrocytes exposed to β/γ radiation or H2O2 were overlapping. Modulations in genes involved in inflammatory response, apoptosis, and proliferation were observed. TSH increased the number and intensity of modulation of differentially expressed genes after 131I exposure.
TSH specifically increased 131I-induced DNA damage probably via a rise in ROS levels and produced a more prominent transcriptomic response after exposure to 131I.
人类甲状腺细胞在接触 131I 后早期的分子事件尚未被阐明。因此，我们研究了 TSH 在原发性培养的人甲状腺细胞中 131I 诱导的 DNA 损伤反应和基因表达中的作用。
在存在或不存在 TSH 的情况下，将甲状腺细胞暴露于 131I（β辐射）、γ辐射（3Gy）和过氧化氢（H2O2）后，我们评估了 DNA 损伤、增殖和细胞周期状态。我们进行了 RNA 测序以分析每种暴露后的基因表达，并评估了 TSH 对每种转录组反应的影响。
总的来说，β或γ辐射和 H2O2 暴露后甲状腺细胞的反应相似。然而，TSH 增加了 131I 诱导的 DNA 损伤，这种效应在碘摄取抑制后部分减弱。具体而言，TSH 增加了未暴露甲状腺细胞中的 DNA 双链断裂数量，从而使它们在接触 131I 后更容易受到损伤。这种效应很可能通过 Gαq 级联和细胞内活性氧（ROS）水平的升高发生。β和γ辐射使甲状腺细胞周期阻滞延长到相似程度，没有凋亡迹象。暴露于β/γ 辐射或 H2O2 的甲状腺细胞的基因表达谱重叠。观察到参与炎症反应、细胞凋亡和增殖的基因的调节。TSH 增加了 131I 暴露后差异表达基因的数量和强度的调节。
TSH 特异性增加了 131I 诱导的 DNA 损伤，可能是通过 ROS 水平的升高引起的，并在接触 131I 后产生更明显的转录组反应。
