title: Dibromoacetic Acid Induces Thymocyte Apoptosis by Blocking Cell Cycle Progression, Increasing Intracellular Calcium, and the Fas/FasL Pathway in Vitro.
abstract: Dibromoacetic acid (DBAA), a haloacetic acid found in drinking water as a disinfection by-product, can cause many adverse effects, including immunotoxicity. In a previous study, we confirmed that DBAA can induce obvious immunotoxicity in mice but that the underlying mechanisms are not clearly understood. In our current study, we confirmed that DBAA induced cytotoxicity and apoptosis in thymocytes isolated from mice by a range of DBAA concentrations (0, 5, 10, 20, or 40 μM). The data showed that DBAA exposure led to a significant decrease in proliferative responses to T-cell mitogens and obvious inhibition in the production of cytokines interleukin-2 and interleukin-4. We found obvious morphological changes of apoptosis in thymocytes and observed the percentage of apoptotic thymocytes to increase significantly as the DBAA concentration increased. Further investigation showed that DBAA can cause G0/G1 arrest in cell cycle analysis, increase intracellular calcium ([Ca(2+)]i) levels, increase the expression of Fas/FasL proteins, and decrease the expression of Bcl-2 protein. It is concluded that in vitro exposure to DBAA can lead to marked cytotoxicity and apoptosis among thymocytes, and the mechanism involved is strongly related to blocking cell cycle progression, increasing intracellular calcium, and increasing Fas/FasL expressions.
authors.affiliation: Department of Toxicological Science, School of Public Health, Harbin Medical University, Harbin, Heilongjiang Province, Peoples' Republic of China.
authors.forename: Shu-Ying
authors.initials: SY
authors.lastname: Gao
authors.affiliation: Department of Occupational Health Science, School of Public Health, Harbin Medical University, Harbin, Heilongjiang Province, Peoples' Republic of China.
authors.forename: Xiao-Rong
authors.initials: XR
authors.lastname: Zhou
authors.affiliation: Department of Toxicological Science, School of Public Health, Harbin Medical University, Harbin, Heilongjiang Province, Peoples' Republic of China.
authors.forename: Ting-Ting
authors.initials: TT
authors.lastname: Gong
authors.affiliation: Environmental Monitoring Centre of Heilongjiang Province, Harbin, Heilongjiang Province, Peoples' Republic of China.
authors.forename: Li-Ming
authors.initials: LM
authors.lastname: Jia
authors.affiliation: Department of Toxicological Science, School of Public Health, Harbin Medical University, Harbin, Heilongjiang Province, Peoples' Republic of China libaix@ems.hrbmu.edu.cn.
authors.forename: Bai-Xiang
authors.initials: BX
authors.lastname: Li
mesh_terms: D000085:Acetates / Q000633:toxicity*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002118:Calcium / Q000032:analysis / Q000378:metabolism*; D002453:Cell Cycle / Q000187:drug effects*; D053222:Fas Ligand Protein / Q000378:metabolism*; D042541:Intracellular Space / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D015398:Signal Transduction / Q000187:drug effects; D060168:Thymocytes / Q000187:drug effects*
chemical_list: D000085:Acetates; D053222:Fas Ligand Protein; C088674:dibromoacetic acid; D002118:Calcium
keywords: Fas/FasL; apoptosis; cell cycle; dibromoacetic acid; immunotoxicity; thymocytes