Ghosh Somiranjan, De Supriyo, Dutta Sisir K
Department of Biology, Howard University, Washington, DC, USA.
Int J Toxicol. 2007 May-Jun;26(3):203-12. doi: 10.1080/10915810701352648.
Polychlorinated biphenyls (PCBs) are a group of persistent and widely distributed environmental pollutants that have various deleterious effects, e.g., neurotoxic, endocrine disruption and reproductive abnormalities, including cancers. Chronic exposure to environmentally hazardous chemicals like PCBs is of great concern to human health. It has been reported earlier that apoptotic proteins change in rats under chronic PCB treatment. It is of importance to determine if chronically exposed human cells develop a different protein expression. In the present study, the authors chronically exposed metabolically competent human liver (HepG2) cells at 50 to 100 microM to examine the role of the well-known environmentally hazardous pollutant non-coplanar 2,2',4,4',5,5'-hexachlorobiphenyl (PCB-153) to study cell death. After 12 weeks of exposure these cells showed significant changes in apoptotic death in subsequent trypan blue growth assay, fluorescence microscopy, DNA fragmentation, and immunoblotting studies. Interestingly, chronically exposed cells showed marked differences in apoptotic and/or death-related proteins (e.g., Bcl2, Bak, and the pro and active forms of caspase-9, which were up-regulated), in contrast to acutely exposed (i.e., 48-h PCB-153 exposed) cells, which maintained linear growth despite repeated exposures. Similarly, tumor suppressor protein p53, proto-oncogene c-myc, and cell cycle regulator protein p21 were also up-regulated compared to nonchronically exposed HepG2 Cells. The results indicated that PCB-153-induced chronic exposure significantly altered different apoptotic (e.g., Bcl2, Bak, caspase-3) and tumor suppressor (e.g., p21, p53, and c-myc) proteins in the cellular model. These results suggest that chronic exposure to PCB-153 can induce cell survival by altering several apoptotic and tumor suppressor proteins.
多氯联苯（PCBs）是一类持久性且广泛分布的环境污染物，具有多种有害影响，例如神经毒性、内分泌干扰以及包括癌症在内的生殖异常。长期接触像多氯联苯这样的环境有害化学物质对人类健康至关重要。此前已有报道称，在慢性多氯联苯处理下大鼠体内的凋亡蛋白会发生变化。确定长期暴露的人类细胞是否会出现不同的蛋白质表达具有重要意义。在本研究中，作者将具有代谢活性的人肝癌（HepG2）细胞长期暴露于50至100微摩尔浓度的环境有害污染物非共平面2,2',4,4',5,5'-六氯联苯（PCB - 153）中，以研究细胞死亡情况。暴露12周后，在随后的台盼蓝生长试验、荧光显微镜检查、DNA片段化和免疫印迹研究中，这些细胞在凋亡死亡方面显示出显著变化。有趣的是，与急性暴露（即暴露于PCB - 153 48小时）的细胞相比，长期暴露的细胞在凋亡和/或死亡相关蛋白（例如Bcl2、Bak以及半胱天冬酶 - 9的前体和活性形式，这些蛋白上调）方面表现出明显差异，急性暴露的细胞尽管反复暴露仍保持线性生长。同样，与未长期暴露的HepG2细胞相比，肿瘤抑制蛋白p53、原癌基因c - myc和细胞周期调节蛋白p21也上调。结果表明，在细胞模型中，PCB - 153诱导的长期暴露显著改变了不同的凋亡蛋白（例如Bcl2、Bak、半胱天冬酶 - 3）和肿瘤抑制蛋白（例如p21、p53和c - myc）。这些结果表明，长期暴露于PCB - 153可通过改变多种凋亡蛋白和肿瘤抑制蛋白来诱导细胞存活。
