Wang Y J, Ho Y S, Jeng J H, Su H J, Lee C C
Department of Environmental and Occupational Health, National Cheng Kung University, Medical College, 138 Sheng-Li Road, 70428, Tainan, Taiwan, ROC.
Chem Biol Interact. 2000 Nov 1;128(3):173-88. doi: 10.1016/s0009-2797(00)00194-0.
Pentachlorophenol (PCP) and its salt are used extensively as biocide and wood preservative. Due to improper disposal, PCP has become an environmental pollutant and is now considered to be ubiquitos. Metabolic studies carried out in rodents or human liver homogenate have indicated that PCP undergoes oxidative dechlorination to form tetrachlorohydroquinone (TCHQ). The cytotoxicity, cell death mechanisms and gene expression of PCP and TCHQ are investigated in human liver and bladder cells and show that TCHQ induces apoptosis and DNA genomic fragmentation in bladder cells but not liver cells. No apoptotic features could be induced by treatment of PCP in both cell lines. The concentrations of PCP required to cause 50% cell death in T-24 and Chang liver cells were 5-10-fold greater than the concentrations of TCHQ. Several gene products are important in controlling the apoptotic and necrotic processes. Of these, hsp 70, CAS, bcl-2 and bax were studied. The expression of the hsp70 gene increased significantly (2-3-fold) in cells treated with TCHQ. However, no significant change was found in the cells treated with PCP. The expression of CAS gene decreased significantly in T-24 cells treated with both TCHQ and PCP. Whereas, no significant change was found in Chang liver cells with the same treatment. In addition, the expression of the bcl-2/bax protein decreased significantly in these two cell lines treated with TCHQ but not PCP.
五氯苯酚（PCP）及其盐类被广泛用作杀生剂和木材防腐剂。由于处置不当，PCP已成为一种环境污染物，现在被认为无处不在。在啮齿动物或人肝匀浆中进行的代谢研究表明，PCP会发生氧化脱氯反应形成四氯对苯二酚（TCHQ）。对人肝细胞和膀胱细胞中PCP和TCHQ的细胞毒性、细胞死亡机制及基因表达进行了研究，结果显示TCHQ可诱导膀胱细胞凋亡和DNA基因组片段化，但对肝细胞无此作用。在这两种细胞系中，PCP处理均未诱导出凋亡特征。在T-24细胞和Chang肝细胞中，导致50%细胞死亡所需的PCP浓度比TCHQ浓度高5至10倍。几种基因产物在控制凋亡和坏死过程中很重要。其中，对热休克蛋白70（hsp 70）、半胱天冬酶相关蛋白（CAS）、bcl-2和bax进行了研究。用TCHQ处理的细胞中，hsp70基因的表达显著增加（2至3倍）。然而，用PCP处理的细胞中未发现显著变化。在用TCHQ和PCP处理的T-24细胞中，CAS基因的表达显著下降。而在相同处理的Chang肝细胞中未发现显著变化。此外，在用TCHQ而非PCP处理的这两种细胞系中，bcl-2/bax蛋白的表达显著下降。
