Gao Shuying, Wang Yan, Zhang Ping, Dong Yucui, Li Baixiang
Department of Toxicological Science, College of Public Health, Harbin Medical University, Harbin, HeiLongjiang Province, Peoples' Republic of China.
Toxicol Sci. 2008 Oct;105(2):331-41. doi: 10.1093/toxsci/kfn139. Epub 2008 Jul 14.
Dibromoacetic acid (DBA) is a haloacetic acid that is present in drinking water as a by-product of chlorinated disinfection. To evaluate its potential adverse health effects, the immunotoxicological effects of DBA on the thymus and spleen of BALB/c mice were investigated. Groups of mice (10 mice per group) were administered DBA at doses of 0, 5, 20, and 50 mg/kg body weight daily for 28 days via oral gavage. The mice orally administered DBA exhibited obvious immunotoxicity, as indicated by changes in the thymus and spleen. DBA induced a dose-dependent decrease and increase in thymus weight and spleen weight, respectively. The histological changes were cortical atrophy of the thymus, white pulp shrinkage of the spleen, and apoptosis of many splenic and thymic lymphocytes; these observations were confirmed by morphometric analysis of the electron microscope scans. Lymphocytes proliferation analysis indicated that the proliferative function of the splenic and thymic lymphocytes was altered after DBA exposure. Cell death via apoptosis was analyzed with an annexin-V/propidium iodide assay by flow cytometry, and we observed that the percentage of apoptosis increased in a dose-dependent manner after DBA treatment. In addition, DBA treatment altered the expression of a few apoptosis-related genes such as Fas, TRAF2, bcl-2, and bax in a dose-dependent manner. Western blot analysis revealed increased expression of the Fas and FasL proteins. In conclusion, DBA induces obvious immunotoxicity in the thymus and spleen, and immune-cell apoptosis mediated by the Fas/FasL pathway may be the potential mechanism underlying this immunotoxicity.
二溴乙酸（DBA）是一种卤乙酸，作为氯化消毒的副产物存在于饮用水中。为评估其潜在的健康不良影响，研究了DBA对BALB/c小鼠胸腺和脾脏的免疫毒理学作用。将小鼠分组（每组10只），通过灌胃法每日给予0、5、20和50 mg/kg体重的DBA，持续28天。口服DBA的小鼠表现出明显的免疫毒性，胸腺和脾脏的变化表明了这一点。DBA分别导致胸腺重量呈剂量依赖性下降和脾脏重量呈剂量依赖性增加。组织学变化为胸腺皮质萎缩、脾脏白髓萎缩以及许多脾细胞和胸腺淋巴细胞凋亡；这些观察结果通过电子显微镜扫描的形态计量分析得到证实。淋巴细胞增殖分析表明，DBA暴露后脾细胞和胸腺淋巴细胞的增殖功能发生改变。通过流式细胞术用膜联蛋白V/碘化丙啶法分析细胞凋亡导致的细胞死亡，我们观察到DBA处理后凋亡百分比呈剂量依赖性增加。此外，DBA处理以剂量依赖性方式改变了一些凋亡相关基因如Fas、TRAF2、bcl-2和bax的表达。蛋白质印迹分析显示Fas和FasL蛋白表达增加。总之，DBA在胸腺和脾脏中诱导明显的免疫毒性，由Fas/FasL途径介导的免疫细胞凋亡可能是这种免疫毒性的潜在机制。
