Dorsey Waneene C, Tchounwou Paul B
Molecular Toxicology Research Laboratory, NIH - Center for Environmental Health, School of Science and Technology, Jackson State University, 1400 Lynch Street, P.O. Box 18540, Jackson, Mississippi, USA.
Int J Environ Res Public Health. 2004 Sep;1(2):90-9. doi: 10.3390/ijerph2004020090.
Pentachlorophenol (PCP) is an organochlorine compound that has been widely used as a biocide in several industrial, agricultural, and domestic applications. Although it has been shown to induce systemic toxicity and carcinogenesis in several experimental studies, the literature is scarce regarding its toxic mechanisms of action at the cellular and molecular levels. Recent investigations in our laboratory have shown that PCP induces cytotoxicity and transcriptionally activates stress genes in human liver carcinoma (HepG2) cells [1]. In this research, we hypothesize that environmental exposure to PCP may trigger cytotoxic, mitogenic, and endocrine-disrupting activities in aquatic organisms including fish. To test this hypothesis, we carried out in vitro cultures of male channel catfish hepatocytes, and performed the fluorescein diacetate assay (FDA) to assess for cell viability, and the Western Blot analysis to assess for vitellogenin expression following exposure to PCP. Data obtained from FDA experiments indicated a strong dose-response relationship with respect to PCP cytotoxicity. Upon 48 hrs of exposure, the chemical dose required to cause 50% reduction in cell viability (LD50) was computed to be 1,987.0 +/- 9.6 microg PCP/mL. The NOAEL and LOAEL were 62.5 +/- 10.3 microg PCP/mL and 125.0+/-15.2 microg PCP/mL, respectively. At lower levels of exposure, PCP was found to be mitogenic, showing a strong dose- and time-dependent response with regard to cell proliferation. Western Blot analysis demonstrated the potential of PCP to cause endocrine-disrupting activity, as evidenced by the up regulation of the 125-kDa vitellogenin protein the hepatocytes of male channel catfish.
五氯苯酚（PCP）是一种有机氯化合物，已在多个工业、农业和家庭应用中广泛用作杀生剂。尽管在多项实验研究中已表明它会诱发全身毒性和致癌作用，但关于其在细胞和分子水平上的毒性作用机制的文献却很少。我们实验室最近的研究表明，PCP可诱导人肝癌（HepG2）细胞产生细胞毒性并转录激活应激基因[1]。在本研究中，我们假设环境暴露于PCP可能会在包括鱼类在内的水生生物中引发细胞毒性、促有丝分裂和内分泌干扰活性。为了验证这一假设，我们对雄性沟鲶肝细胞进行了体外培养，并进行了荧光素二乙酸酯测定（FDA）以评估细胞活力，以及进行蛋白质印迹分析以评估暴露于PCP后卵黄蛋白原的表达。从FDA实验获得的数据表明，PCP细胞毒性存在很强的剂量反应关系。暴露48小时后，导致细胞活力降低50%所需的化学剂量（LD50）经计算为1,987.0 +/- 9.6微克PCP/毫升。无观察到有害作用水平（NOAEL）和最低观察到有害作用水平（LOAEL）分别为62.5 +/- 10.3微克PCP/毫升和125.0 +/- 15.2微克PCP/毫升。在较低暴露水平下，发现PCP具有促有丝分裂作用，在细胞增殖方面表现出很强的剂量和时间依赖性反应。蛋白质印迹分析表明，PCP具有导致内分泌干扰活性的潜力，雄性沟鲶肝细胞中125 kDa卵黄蛋白原蛋白的上调证明了这一点。
