The Department of Toxicology, School of Public Health, Hebei Medical University, Zhongshan East Road 361, Shijiazhuang, 050017 Hebei, PR China.
Int J Hyg Environ Health. 2011 Mar;214(2):145-50. doi: 10.1016/j.ijheh.2011.01.008. Epub 2011 Mar 1.
Tributyltin chloride (TBTC), a characteristic organotin compound, is widely used as an agricultural pesticide, as a stabiliser for polyvinyl-chloride plastics and in antifouling paints for ship hulls. Organotin compounds are known to produce toxicity in the immune system, but the mechanism underlying this immunotoxicity remains unclear. In this study, we evaluated the immunotoxic effect of TBTC on the acquired immune response, and we investigated the involvement of thymocyte apoptosis and Fas expression in the observed immunotoxicity of TBTC. Mice were randomly assigned to four groups (10 mice per group) and treated with TBTC at doses of 0, 0.5, 4 and 20 mg/kg by oral gavage for 28 days. Following TBTC administration, animals were sacrificed, and morphologic changes in the thymus and spleen were assessed. Atrophy in both the thymus and spleen was observed in all groups treated with TBTC, and the relative organ weight in the highest TBTC group (20 mg/kg) was significantly lower than that observed in the control group. We also conducted assays to assess the cellular and humoral functional responses such as plaque-forming cell assay (PFC), lymphocyte proliferation test and delayed-type hypersensitivity (DTH) response to SRBC. Our results indicate that at doses of 4 mg/kg and 20 mg/kg, TBTC could significantly suppress both the humoral and cellular immune responses when compared to the control group (p<0.05). In addition, immunohistochemical staining and flow cytometry analysis were carried out to measure the expression of Fas and thymocyte apoptosis, respectively. We observed a dose-dependent increase in thymocyte apoptosis and that Fas expression in the TBTC-treated groups (4 mg/kg and 20 mg/kg) was significantly enhanced when compared to the control group. Correlation analysis demonstrated a positive linear correlation between apoptosis and Fas expression, indicating that TBTC-induced thymocyte apoptosis may be mediated by Fas expression. Taken together, our data clearly demonstrate that TBTC-induced immunotoxicity is associated with thymocyte apoptosis and that this process is mediated by the Fas pathway.
三丁基锡氯化物（TBTC）是一种特征性的有机锡化合物，被广泛用作农业杀虫剂、聚氯乙烯塑料稳定剂和船体防污漆。有机锡化合物被认为会对免疫系统产生毒性，但这种免疫毒性的机制尚不清楚。在这项研究中，我们评估了 TBTC 对获得性免疫反应的免疫毒性作用，并研究了胸腺细胞凋亡和 Fas 表达在 TBTC 观察到的免疫毒性中的作用。将小鼠随机分为四组（每组 10 只），通过口服灌胃给予 TBTC 剂量为 0、0.5、4 和 20mg/kg，连续 28 天。给予 TBTC 后，处死动物，评估胸腺和脾脏的形态变化。在所有接受 TBTC 治疗的组中，均观察到胸腺和脾脏的萎缩，并且最高 TBTC 组（20mg/kg）的相对器官重量明显低于对照组。我们还进行了细胞和体液功能反应的测定，如溶血空斑形成细胞试验（PFC）、淋巴细胞增殖试验和迟发型超敏反应（DTH）对 SRBC 的反应。我们的结果表明，在 4mg/kg 和 20mg/kg 剂量下，与对照组相比，TBTC 可显著抑制体液和细胞免疫反应（p<0.05）。此外，进行了免疫组织化学染色和流式细胞术分析，分别测量 Fas 的表达和胸腺细胞凋亡。我们观察到，与对照组相比，TBTC 处理组（4mg/kg 和 20mg/kg）的胸腺细胞凋亡和 Fas 表达呈剂量依赖性增加。相关性分析表明，凋亡和 Fas 表达之间存在正线性相关，表明 TBTC 诱导的胸腺细胞凋亡可能是由 Fas 表达介导的。综上所述，我们的数据清楚地表明，TBTC 诱导的免疫毒性与胸腺细胞凋亡有关，并且这个过程是由 Fas 途径介导的。
