Tang Y, Donnelly K C, Tiffany-Castiglioni E, Mumtaz M M
Department of Veterinary Anatomy and Public Health, Texas A&M University, College Station, TX 77843-4458, USA.
J Toxicol Environ Health A. 2003 May 23;66(10):919-40. doi: 10.1080/15287390306455.
Polycyclic aromatic hydrocarbons (PAHs) are a major class of environmental pollutants. These chemicals are the products of incomplete combustion and are present in every compartment of the environment. While the carcinogenic potential of these chemicals has been investigated in numerous studies, very little is known about the potential of these chemicals to produce damage to neural cells. The objective of this study was to investigate the toxicity of several model PAHs and binary mixtures of these chemicals in neural cells. Chemicals tested included benzo[a]pyrene (BaP), chrysene, anthracene, and pentachlorophenol (PCP). Four end points, including amino acid incorporation, total protein, total cell count, and viable cells (trypan dye exclusion), were measured in SY5Y human neuroblastoma cells and C6 rat glioma cells. The most sensitive measure of PAH toxicity in neural cells was amino acid incorporation into proteins. BaP was the most toxic of all PAHs tested, and anthracene failed to produce a toxic response at any concentration tested. Without metabolic activation, BaP induced a significant cytotoxic response at a concentration of 30 microM. With activation (0.25% S9), BaP induced a response at concentration levels of 3 microM and 30 microM. Minimal toxicity was observed with chrysene at the highest concentration tested, and anthracene failed to produce a toxic response at any concentration tested. With mixtures of PAHs the majority of samples induced additive responses. The minimum concentration required to induce a significant response was reduced for the mixture of chrysene and BaP when compared to BaP alone. In addition, PCP appeared to increase the inhibition of acetylcholinesterase by mipafox. The data suggest that PAHs are capable of producing damage to neural cells only at concentrations that are near their solubility limits.
多环芳烃（PAHs）是一类主要的环境污染物。这些化学物质是不完全燃烧的产物，存在于环境的各个部分。虽然在众多研究中已经对这些化学物质的致癌潜力进行了调查，但对于它们对神经细胞造成损伤的潜力却知之甚少。本研究的目的是调查几种典型PAHs及其二元混合物对神经细胞的毒性。所测试的化学物质包括苯并[a]芘（BaP）、屈、蒽和五氯苯酚（PCP）。在SY5Y人神经母细胞瘤细胞和C6大鼠胶质瘤细胞中测量了四个终点指标，包括氨基酸掺入、总蛋白、总细胞计数和活细胞（台盼蓝排斥法）。神经细胞中PAH毒性最敏感的指标是氨基酸掺入蛋白质。在所测试的所有PAHs中，BaP毒性最大，而蒽在任何测试浓度下均未产生毒性反应。在没有代谢活化的情况下，BaP在浓度为30微摩尔时诱导了显著的细胞毒性反应。在有活化剂（0.25% S9）的情况下，BaP在3微摩尔和30微摩尔的浓度水平下诱导了反应。在所测试的最高浓度下，屈的毒性最小，而蒽在任何测试浓度下均未产生毒性反应。对于PAHs混合物，大多数样品诱导了加和反应。与单独的BaP相比，屈和BaP混合物诱导显著反应所需的最低浓度降低。此外，PCP似乎增加了米帕明对乙酰胆碱酯酶的抑制作用。数据表明，PAHs只有在接近其溶解度极限的浓度下才能够对神经细胞造成损伤。
