BIS(TRI-N-BUTYLTIN)OXIDE INDUCES PROGRAMMED CELL-DEATH (APOPTOSIS) IN IMMATURE RAT THYMOCYTES
BIS(TRI-N-BUTYLTIN)OXIDE INDUCES PROGRAMMED CELL-DEATH (APOPTOSIS) IN IMMATURE RAT THYMOCYTES
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DOI：
10.1007/bf02034940
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发表时间：
1991-01-01
影响因子：
6.1
通讯作者：
COHEN, GM
中科院分区：
文献类型：
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作者：
RAFFRAY, M;COHEN, GM
为探讨免疫毒性有机锡化合物二(三丁基锡)氧化物(TBTO)对淋巴样细胞的细胞毒性机制，将幼年大鼠胸腺细胞暴露于TBTO(0.1-5-mU-M)中6h，在较低浓度的TBTO(0.1和1-mU-M)下，活体染色显示仅出现边缘活性丧失，尽管形态学研究显示具有异常特征的细胞数量增加，表明细胞程序性死亡(凋亡)。这些改变包括核染色质凝集(与DNA片段化增加有关)、细胞质收缩和形成膜结合的凋亡小体。当用琼脂糖凝胶电泳法显示时，基因组DNA呈现为一系列重复倍数为180-200个碱基对的片段。在与10-mU-M甲基强的松龙琥珀酸酯(MPS)孵育的胸腺细胞中，类似的形态变化和DNA裂解成寡核体片段也很明显。MPS是一种糖皮质激素，已知能诱导胸腺细胞程序性细胞死亡。在与5-mU-M TBTO孵育的胸腺细胞中，观察到明显的细胞毒性，伴随着指示坏死的变性变化。这些发现表明，在不明显的细胞毒性水平下，TBTO能够诱导大鼠胸腺细胞的程序性细胞死亡。这提示了先前报道的TBTO体内T细胞免疫缺陷的可能机制。
In order to characterise the mechanism of cytotoxicity of the immunotoxic organotin compound bis(tri-n-butyltin)oxide (TBTO) to lymphoid cells, isolated thymocytes from immature rats were exposed to TBTO (0.1-5-mu-M) for up to 6 h. At lower TBTO concentrations (0.1 and 1-mu-M) vital staining showed that only marginal loss of viability occured, although morphological studies demonstrated increased numbers of cells with abnormal features indicative of programmed cell death (apoptosis). These changes included nuclear chromatin condensation (which was associated with increased DNA fragmentation), cytoplasmic contraction and formation of membrane bound apoptotic bodies. When visualised by agarose gel electrophoresis, genomic DNA appeared as a series of fragments with a repeat multiple of 180-200 base pairs. Comparable morphological changes and cleavage of DNA into oligonucleosomal fragments were evident in thymocytes incubated with 10-mu-M methyl prednisolone hemisuccinate (MPS); a glucocorticoid hormone known to induce programmed cell death in thymocytes. Marked cytotoxicity associated with degenerative changes indicative of necrosis was observed in thymocytes incubated with 5-mu-M TBTO. These findings indicate that, at levels which are not overtly cytotoxic, TBTO is capable of inducing programmed cell death in rat thymocytes. This suggests a possible mechanism for the T-cell immunodeficiency previously reported for TBTO in vivo.