Michałowicz Jaromir, Sicińska Paulina
Department of Environmental Pollution Biophysics, University of Łódź, Banacha Str. 12/16, 90-237 Łódź, Poland.
Toxicol Lett. 2009 Dec 15;191(2-3):246-52. doi: 10.1016/j.toxlet.2009.09.010. Epub 2009 Sep 18.
In this work the effect of 2,4,5-trichlorophenol (2,4,5-TCP), pentachlorophenol (PCP), 4,6-dichloroguaiacol (4,6-DCG), tetrachloroguaiacol (TeCG), 4,5-dichlorocatechol (4,5-DCC) and tetrachlorocatechol (TeCC) on the induction of apoptosis in human peripheral blood lymphocytes was examined. The analysis of the changes in mitochondrial transmembrane potential (DeltaPsi(m)) was performed using JC-9 fluorescent probe. It was noted that all the compounds studied (excluding 4,6-DCG) in a dose-dependent manner (0.2-25 ppm) increased the number of cells, which were characterized by the DeltaPsi(m) reduction, with the strongest effect observed for TeCG and TeCC. Moreover, fluorimetric assay of the caspase-3 activity revealed that 2,4,5-TCP, chlorocatechols and TeCG in the range of the concentrations of 1-50 ppm increased the caspase-3 expression, whereas PCP in its highest concentration of 50 ppm decreased the activity of this enzyme. It was also noted that the caspase-3 activity was the most strongly induced by tetrachlorocatechols, particularly by TeCC. The analysis of YO-PRO-1 iodide/propidum iodide staining revealed that TeCC, the most strongly increased the number of apoptotic cells at 5 and 25 ppm, whereas at a dose of 100 ppm the strongest effect on apoptosis induction was observed for 2,4,5-TCP.
在本研究中，检测了2,4,5-三氯苯酚（2,4,5-TCP）、五氯苯酚（PCP）、4,6-二氯愈创木酚（4,6-DCG）、四氯愈创木酚（TeCG）、4,5-二氯儿茶酚（4,5-DCC）和四氯儿茶酚（TeCC）对人外周血淋巴细胞凋亡诱导的影响。使用JC-9荧光探针分析线粒体跨膜电位（ΔΨm）的变化。结果发现，所有研究的化合物（不包括4,6-DCG）在0.2 - 25 ppm的剂量范围内均呈剂量依赖性增加了以ΔΨm降低为特征的细胞数量，其中TeCG和TeCC的作用最强。此外，caspase-3活性的荧光测定显示，1 - 50 ppm浓度范围内的2,4,5-TCP、氯儿茶酚和TeCG增加了caspase-3的表达，而50 ppm最高浓度的PCP降低了该酶的活性。还发现四氯儿茶酚，尤其是TeCC，对caspase-3活性的诱导作用最强。YO-PRO-1碘化物/碘化丙啶染色分析表明，TeCC在5和25 ppm时最强烈地增加了凋亡细胞的数量，而在100 ppm剂量下，2,4,5-TCP对凋亡诱导的作用最强。
