Subramoniam A, Khandelwal S, Dwivedi P D, Khanna S, Shanker R
Immunotoxicology Division, Industrial Toxicology Research Centre, Lucknow, India.
Immunopharmacol Immunotoxicol. 1994 Nov;16(4):645-77. doi: 10.3109/08923979409019744.
A marked dose dependent reduction in thymus weight and its nucleated cell counts with histological alterations was observed in rats exposed to oral dibutyltin dilaurate (DBTL) for 2 weeks at 2, 4, 8 or 16 mg/kg body weight. The incorporation of [3H]-inositol into all the three major phosphoinositides was drastically reduced in thymocytes in a dose dependent manner. Furthermore, the basal and the mitogen (Con A) stimulated [3H]-inositol phosphates generation was diminished significantly in 8 mg DBTL group. However, in vitro incubation of DBTL with thymocytes failed to evoke any change in phosphoinositide hydrolysis. Similarly, a time and dose dependent inhibition in phosphoinositide synthesis with as high as 80% by 10 microM DBTL was exhibited under in vitro conditions. A 130% and 600% enhancement of protein kinase C (PKC) activity in thymocytes was seen in 4 mg and 8 mg DBTL group, respectively. Addition of DBTL to the cell free assay system of thymocytes resulted in a concentration dependent activation of the enzyme activity. A dose dependent increase in intracellular calcium was also evident when DBTL was added to thymocytes under in vitro conditions. These results are of significance and may bear close relationship to the observed thymic atrophy by DBTL.
给大鼠按2、4、8或16mg/kg体重经口给予二月桂酸二丁基锡（DBTL）2周后，观察到胸腺重量及其有核细胞计数显著的剂量依赖性降低，并伴有组织学改变。胸腺细胞中[3H]-肌醇掺入所有三种主要磷酸肌醇的量呈剂量依赖性急剧减少。此外，在8mg DBTL组中，基础和有丝分裂原（Con A）刺激的[3H]-肌醇磷酸生成显著减少。然而，DBTL与胸腺细胞的体外孵育未能引起磷酸肌醇水解的任何变化。同样，在体外条件下，10μM DBTL对磷酸肌醇合成的抑制呈时间和剂量依赖性，高达80%。在4mg和8mg DBTL组中，胸腺细胞中蛋白激酶C（PKC）活性分别增强了130%和600%。将DBTL添加到胸腺细胞的无细胞测定系统中导致酶活性的浓度依赖性激活。在体外条件下，将DBTL添加到胸腺细胞中时，细胞内钙也呈剂量依赖性增加。这些结果具有重要意义，可能与DBTL引起的胸腺萎缩密切相关。
