Falahatpisheh M H, Donnelly K C, Ramos K S
Center for Environmental and Rural Health, Texas A&M University College of Veterinary Medicine, College Station 77843-4466, USA.
J Toxicol Environ Health A. 2001 Apr 6;62(7):543-60. doi: 10.1080/152873901300007833.
Although the liver and pulmonary toxicity of polycyclic aromatic hydrocarbons (PAHs) has been extensively characterized, limited data concerning the nephrotoxic potential of these chemicals are available. The present studies were conducted to define the kidney cell-specific toxic responses to anthracene (ANTH), benzo[a]pyrene (BaP), and chrysene (CHRY). Given that exposure to environmental chemicals from a specific source is rarely limited to a single compound, a second goal was to evaluate the nephrotoxic potential of binary and ternary mixtures of these chemicals. Cultured rat glomerular mesangial cells (rGMCs) and porcine cortico-tubular epithelial kidney cells (LLCPK-1) were challenged with hydrocarbon concentrations ranging from 0.03 to 30 microM for up to 24 h and were processed for measurements of mitochondrial membrane permeability, trypan blue dye exclusion, cytoplasmic enzyme leakage, and protein synthesis. BaP induced a threefold increase in mitochondrial fragility, a modest increase in cellular death, and 40% decrease in the rate of protein synthesis in rGMCs. Anthracene was also cytotoxic to rGMCs, inducing a twofold increase in mitochondrial fragility and a 40% decrease in the rate of protein synthesis, but no changes in cellular viability. Although CHRY was devoid of toxicity to rGMCs, a 40% decrease in the rate of protein synthesis was observed in LLCPK-1 cells treated with this hydrocarbon. BaP and ANTH were not overtly cytotoxic to LLCPK-1 cells at any of the concentrations tested. Binary and ternary mixtures of BaP with ANTH and CHRY in rGMCs, and mixtures of CHRY with ANTH and BaP in LLCPK-1 cells, yielded antagonistic interactions. Based on these data, it is concluded that PAHs exhibit chemical- and cell-specific nephrotoxicity, but that toxicological outcomes are influenced by the presence of multiple hydrocarbons in complex mixtures.
尽管多环芳烃（PAHs）对肝脏和肺部的毒性已得到广泛研究，但关于这些化学物质肾毒性潜力的数据却很有限。本研究旨在确定肾细胞对蒽（ANTH）、苯并[a]芘（BaP）和屈（CHRY）的特异性毒性反应。鉴于从特定来源接触环境化学物质很少仅限于单一化合物，第二个目标是评估这些化学物质二元和三元混合物的肾毒性潜力。用浓度范围为0.03至30 microM的碳氢化合物对培养的大鼠肾小球系膜细胞（rGMCs）和猪肾小管上皮肾细胞（LLCPK - 1）进行长达24小时的刺激，并对其进行处理以测量线粒体膜通透性、台盼蓝染料排斥、细胞质酶泄漏和蛋白质合成。BaP使rGMCs中线粒体脆性增加了三倍，细胞死亡略有增加，蛋白质合成速率降低了40%。蒽对rGMCs也具有细胞毒性，使线粒体脆性增加了两倍，蛋白质合成速率降低了40%，但细胞活力没有变化。尽管CHRY对rGMCs没有毒性，但在用这种碳氢化合物处理的LLCPK - 1细胞中观察到蛋白质合成速率降低了40%。在任何测试浓度下，BaP和ANTH对LLCPK - 1细胞都没有明显的细胞毒性。BaP与ANTH和CHRY在rGMCs中的二元和三元混合物，以及CHRY与ANTH和BaP在LLCPK - 1细胞中的混合物，产生了拮抗作用。基于这些数据，可以得出结论，PAHs表现出化学和细胞特异性的肾毒性，但毒理学结果受复杂混合物中多种碳氢化合物的存在影响。
