ToxSci Advance Access originally published online on July 14, 2008
Toxicological Sciences 2008 105(2):331-341; doi:10.1093/toxsci/kfn139
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Subacute Oral Exposure to Dibromoacetic Acid Induced Immunotoxicity and Apoptosis in the Spleen and Thymus of the mice
* Department of Toxicological Science, College of Public Health, Harbin Medical University, Harbin, HeiLongjiang Province, Peoples' Republic of China, 150081
Department of Immunological Science, College of Preclinical Medicine, Harbin Medical University, Harbin, HeiLongjiang Province, Peoples’ Republic of China, 150081
1 To whom correspondence should be addressed at Department of Toxicological Science, College of Public Health, Harbin Medical University, Harbin, HeiLongJiang Province, Peoples' Republic of China, 150081. Fax: (86) 451-87502829. E-mail: libaix{at}ems.hrbmu.edu.cn.
Received March 16, 2008; accepted June 30, 2008
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Abstract |
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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.
Key Words: dibromoacetic acid; immunotoxicity; apoptosis; mice.