Evidence for the induction of apoptosis in thymocytes by 2,3,7,8-tetvachlorodibenzo-p-dioxin in vivo
Evidence for the induction of apoptosis in thymocytes by 2,3,7,8-tetvachlorodibenzo-p-dioxin in vivo
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DOI：
10.1006/taap.1996.8049
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发表时间：
1997-02-01
影响因子：
3.8
通讯作者：
Nagarkatti, M
中科院分区：
文献类型：
--
作者：
Kamath, AB;Xu, HM;Nagarkatti, M
2,3,7,8-四氯二苯并-对二恶英 (TCDD) 因其免疫毒性作用（尤其是对胸腺的免疫毒性作用）而闻名。 TCDD 引起胸腺萎缩的确切机制尚不清楚。在本研究中，我们通过使用TdT介导的FITC-dUTP缺口末端标记方法并通过流式细胞术分析细胞，研究了TCDD在体内施用时是否引发胸腺细胞凋亡。注射 TCDD 后 8-12 小时检测到显着的细胞凋亡，但在 24 小时或更长（研究长达 120 小时）时未检测到。此外，使用 JAM 测试证实了细胞凋亡的诱导，其中用 [H-3] 胸苷标记的 TCDD 处理小鼠的胸腺细胞与对照组相比，表现出 DNA 碎片增加。与 TCDD 治疗类似，给予 C57BL/6 小鼠地塞米松（5 或 100 mg/kg）会引发细胞凋亡，仅在给药后 12 小时检测到细胞凋亡，此后则不再检测到。当来自 TCDD 或地塞米松处理的小鼠的胸腺细胞在体外培养 24 小时时，与媒介物处理的对照相比，它们表现出细胞凋亡的显着增加。然而，当将 TCDD 添加到胸腺细胞的体外培养物中时，未能引发细胞凋亡。总之，我们的研究表明 TCDD 可以诱导体内胸腺细胞凋亡。这只能在 TCDD 施用后的早期阶段检测到，可能是因为体内吞噬细胞快速清除凋亡细胞。 (C) 1997 年学术出版社。
2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is well known for its immunotoxic effects particularly on the thymus. The exact mechanism by which TCDD induces thymic atrophy is not clear. In the current study, we investigated whether TCDD triggers apoptosis in thymocytes, when administered in vivo, by using the TdT-mediated FITC - dUTP nick end labeling method and analyzing the cell flow cytometrically. Significant apoptosis was detected at 8-12 hr after the TCDD injection but not at 24 hr or beyond, up to 120 hr of study. Furthermore, the induction of apoptosis was confirmed using the JAM test in which thymocytes from TCDD-treated mice, labeled with [H-3]thymidine, exhibited increased DNA fragmentation when compared to the controls. Similar to TCDD treatment, administration of dexamethasone (5 or 100 mg/kg) into C57BL/6 mice triggered apoptosis that was only detected at 12 hr after administration of the drug and not thereafter. When thymocytes from TCDD- or dexamethasone-treated mice were cultured in vitro for 24 hr, they exhibited marked increase in apoptosis when compared to the vehicle-treated controls. However, TCDD, when added to in vitro cultures of thymocytes, failed to trigger apoptosis. Together, our studies demonstrate that TCDD can induce apoptosis in thymocytes in vivo. This can be detected only at an early stage following TCDD administration, possibly because of rapid clearance of apoptotic cells by the phagocytic cells in vivo. (C) 1997 Academic Press.