Laboratory of Cellular Signaling, Faculty of Integrated Arts and Sciences, The University of Tokushima, Minami-Jyozanjima 1-1, Tokushima 770-8502, Japan.
Environ Toxicol Pharmacol. 2003 Jan;13(1):29-36. doi: 10.1016/s1382-6689(02)00127-8.
As tri-n-butyltin (TBT), one of the environmental pollutants, is accumulated in wild animals, concern regarding the toxicity of TBT in both wildlife and human is increasing. TBT has been reported to increase intracellular Ca(2+) concentration in several types of cells. In order to examine how Ca(2+) is involved in TBT-induced cell death, the effect of TBT on rat thymocytes has been compared with that of A23187, a calcium ionophore, under various concentrations of external Ca(2+) using a flow cytometer and fluorescent probes. Although both TBT and A23187 were toxic to cells under normal Ca(2+) condition, under external Ca(2+)-free condition the cytotoxic action of TBT was potentiated without changing the threshold concentration while that of A23187 was completely abolished. A23187 attenuated the TBT-induced descent in cell viability under normal Ca(2+) concentration despite intracellular Ca(2+) concentration was increased. As external Ca(2+) concentration increased, the TBT-induced increase in number of dead cells gradually decreased whereas the number of cells in an early stage of apoptosis increased. Results suggest that Ca(2+) has contradictory actions on the process of TBT-induced cell death in rat thymocytes.
作为一种环境污染物，三丁基锡（TBT）在野生动物体内积累，人们对 TBT 在野生动物和人类中的毒性的担忧日益增加。已有报道称，TBT 会增加几种类型细胞内的 Ca(2+)浓度。为了研究 Ca(2+)如何参与 TBT 诱导的细胞死亡，使用流式细胞仪和荧光探针，在不同浓度的外 Ca(2+)条件下，比较了 TBT 对大鼠胸腺细胞的作用和钙离子载体 A23187 的作用。虽然 TBT 和 A23187 在正常 Ca(2+)条件下对细胞都有毒性，但在无外 Ca(2+)条件下，TBT 的细胞毒性作用增强，而阈浓度不变，而 A23187 的作用则完全被抑制。尽管细胞内 Ca(2+)浓度升高，A23187 仍能减弱 TBT 在正常 Ca(2+)浓度下诱导的细胞活力下降。随着外 Ca(2+)浓度的增加，TBT 诱导的死亡细胞数量逐渐减少，而处于早期凋亡阶段的细胞数量增加。结果表明，Ca(2+)对大鼠胸腺细胞中 TBT 诱导的细胞死亡过程有相反的作用。
