title: Induction of p53-mediated apoptosis in splenocytes and thymocytes of C57BL/6 mice exposed to perfluorooctane sulfonate (PFOS).
abstract: Perfluorooctane sulfonate (PFOS) is a persistent environmental contaminant found in human and wildlife tissues. It has been reported that PFOS can cause atrophy of the immune organs and apoptosis of immunocytes in rodents. However, the mechanism behind such cause is still unclear. To understand the model of cell death and its mechanism on lymphoid cells in vivo, we conducted a dose/response experiment in which 4 groups of male adult C57BL/6 mice (12 mice per group) were dosed daily by oral gavage with PFOS at 0, 0.0167, 0.0833, or 0.8333mg/kg/day, yielding targeted Total Administered Dose (TAD) of 0, 1, 5, or 50mg PFOS/kg, respectively, over 60days. The results showed that spleen and thymus weight were significantly reduced in the highest PFOS-dose-group (TAD 50mg PFOS/kg) compared to the control group, whereas liver weight was significantly increased. We analyzed the cell death via apoptosis with an annexin-V/propidium iodide assay by flow cytometry, and observed that both the percentage of apoptosis and the expression of the pro-apoptotic proteins p53 in splenocytes and thymocytes increased in a dose-related manner after PFOS treatment. We also observed that PFOS induced p53-dependent apoptosis through the cooperation between the Bcl-xl down regulation without changing the Bcl-2 and Bax expression. The down regulation of Bcl-xl was strongly indicating mitochondrial involvement in apoptosis. It is confirmed by the release of cytochrome c and activation of caspase-3. All of these findings establish an important role of p53 and mitochondrial function in PFOS induced toxic environment in the host.
authors.affiliation: School of Public Health, China Medical University, Shenyang 110001, PR China. ghdong@mail.cmu.edu.cn
authors.forename: Guang-Hui
authors.initials: GH
authors.lastname: Dong
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.forename: Ying-Hua
authors.initials: YH
authors.lastname: Zhang
authors.forename: Miao-Miao
authors.initials: MM
authors.lastname: Liu
authors.forename: Da
authors.initials: D
authors.lastname: Wang
authors.forename: Li
authors.initials: L
authors.lastname: Zheng
authors.forename: Yi-He
authors.initials: YH
authors.lastname: Jin
mesh_terms: D017738:Alkanesulfonic Acids / Q000097:blood / Q000633:toxicity*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D051033:Apoptosis Inducing Factor / Q000378:metabolism; D053148:Caspase 3 / Q000096:biosynthesis; D002452:Cell Count; D002453:Cell Cycle / Q000187:drug effects; D002469:Cell Separation; D002470:Cell Survival / Q000187:drug effects; D045304:Cytochromes c / Q000096:biosynthesis; D005434:Flow Cytometry; D005466:Fluorocarbons / Q000097:blood / Q000633:toxicity*; D007166:Immunosuppressive Agents / Q000097:blood / Q000633:toxicity*; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D009336:Necrosis; D009929:Organ Size / Q000187:drug effects; D013154:Spleen / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D060168:Thymocytes / Q000187:drug effects* / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000502:physiology*; D051028:bcl-2-Associated X Protein / Q000096:biosynthesis; D051020:bcl-X Protein / Q000096:biosynthesis / Q000235:genetics
chemical_list: D017738:Alkanesulfonic Acids; D051033:Apoptosis Inducing Factor; D005466:Fluorocarbons; D007166:Immunosuppressive Agents; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein; D045304:Cytochromes c; C076994:perfluorooctane sulfonic acid; D053148:Caspase 3