Neurotoxicity of polycyclic aromatic hydrocarbons and simple chemical mixtures.
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.
Tang
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Y
Department of Veterinary Anatomy and Public Health, Texas A&M University, College Station, TX 77843-4458, USA.
Donnelly
K C
KC
Tiffany-Castiglioni
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Mumtaz
M M
MM
D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D002800:Cholinesterase Inhibitors / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005910:Glioma; D006801:Humans; D007531:Isoflurophate / Q000031:analogs & derivatives* / Q000633:toxicity; D009447:Neuroblastoma; D009457:Neuroglia / Q000187:drug effects* / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D011084:Polycyclic Aromatic Hydrocarbons / Q000378:metabolism / Q000633:toxicity*; D014176:Protein Biosynthesis; D051381:Rats; D012680:Sensitivity and Specificity; D014407:Tumor Cells, Cultured
D000596:Amino Acids; D002800:Cholinesterase Inhibitors; D011084:Polycyclic Aromatic Hydrocarbons; D007531:Isoflurophate; C005238:mipafox