2,3,7,8-TETRACHLORODIBENZO-PARA-DIOXIN KILLS IMMATURE THYMOCYTES BY CA-2+-MEDIATED ENDONUCLEASE ACTIVATION
2,3,7,8-TETRACHLORODIBENZO-PARA-DIOXIN KILLS IMMATURE THYMOCYTES BY CA-2+-MEDIATED ENDONUCLEASE ACTIVATION
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DOI：
10.1126/science.3262923
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发表时间：
1988-10-14
期刊：
影响因子：
56.9
通讯作者：
ORRENIUS, S
中科院分区：
文献类型：
--
作者：
MCCONKEY, DJ;HARTZELL, P;ORRENIUS, S
将幼鼠的胸腺细胞悬浮液与 2,3,7,8-四氯二苯并-对二恶英 (TCDD) 一起孵育，导致胞质游离 Ca2+ 浓度持续增加，随后出现 DNA 断裂和细胞活力丧失。用蛋白质合成抑制剂放线菌酮处理的细胞中，Ca2+ 增加和 DNA 断裂均被阻止，而当细胞在“无 Ca2+”培养基中孵育或用高浓度钙探针 quin-2 四乙酰氧基甲酯预处理时，未检测到 DNA 断裂和细胞杀伤。这些结果表明，TCDD 可以通过启动类似于先前描述的糖皮质激素的自杀过程来杀死未成熟的胸腺细胞。
Suspensions of thymocytes from young rats were incubated with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), which resulted in a sustained increase in cytosolic free Ca2+ concentration followed by DNA fragmentation and loss of cell viability. Both the Ca2+ increase and DNA fragmentation were prevented in cells treated with the inhibitor of protein synthesis, cycloheximide, and DNA fragmentation and cell killing were not detected when cells were incubated in a "Ca2+-free" medium or pretreated with high concentrations of the calcium probe, quin-2 tetraacetoxymethyl ester. These results indicate that TCDD can kill immature thymocytes by initiating a suicide process similar to that previously described for glucocorticoid hormones.