Antagonistic interactions among nephrotoxic polycyclic aromatic hydrocarbons

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 μM 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.