Immunotoxicity of a reconstituted polynuclear aromatic hydrocarbon mixture in B6C3F1 mice.
Previous studies on the immunotoxicity of a complex mixture of polynuclear aromatic hydrocarbon (PAH) by-products from a manufactured gas plant indicated possible synergistic interactions which were investigated by determining the immunosuppressive effects of a reconstituted PAH mixture in female B6C3F1 mice challenged with TNP-haptenated sheep red blood cells (SRBCs) (T-cell-dependent) or trinitrophenyl-lipopolysaccharide (TNP-LPS) (T-cell-independent) antigens. The reconstituted PAH mixture contained the following 17 congeners: 2-rings (indan, naphthalene, 1- and 2-methylnaphthalene), 3-rings (acenaphthylene, acenaphthene, dibenzofuran, fluorene, phenanthrene and anthracene), and > or = 4-rings (pyrene, fluoranthene, benz[a]anthracene, chrysene, benzo[b]fluoranthene, benzo[k]fluoranthene and benzo[a]pyrene), and resembled mixtures identified as by-products from manufactured gas plants. The reconstituted mixture and the 2-, 3- and > or = 4-ring PAH fractions all caused a dose-dependent decrease in the splenic plaque-forming cell (PFC) response to SRBCs or TNP-LPS, and their ED50 values for the four treatment groups were 86, 354, 145, and 23 or 163, 439, 637 and 31 mg/kg, respectively. The corresponding ED50 values for decreased serum anti-TNP IgM levels for these same mixtures were (TNP-haptenated SRBCs, T-cell-dependent) 144, 231, 42 and 27 units, respectively, and (TNP-LPS, T-cell-independent) 161, 406, 312 and 69 units, respectively. The suppression of anti-TNP IgM titers was similar to the suppression of the PFC response and shows that antigen-specific immunoglobulin titer can be used as a biomarker of PAH exposure. A direct comparison of the immunotoxic responses of the reconstituted PAH mixture and the corresponding dose of the > or = 4-ring PAHs indicated that the latter fraction was primarily responsible for the activity of the reconstituted mixture.
Harper
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Veterinary Physiology and Pharmacology, Texas A & M University, College Station, 77843-4466, USA.
Steinberg
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M
Safe
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S
D000818:Animals; D002273:Carcinogens / Q000008:administration & dosage / Q000633:toxicity*; D002452:Cell Count / Q000187:drug effects; D005591:Chemical Fractionation; D004305:Dose-Response Relationship, Drug; D004731:Endotoxins / Q000008:administration & dosage / Q000633:toxicity; D004912:Erythrocytes / Q000166:cytology; D005260:Female; D006241:Haptens / Q000008:administration & dosage / Q000633:toxicity; D006462:Hemolytic Plaque Technique; D007165:Immunosuppression Therapy; D000922:Immunotoxins / Q000008:administration & dosage / Q000633:toxicity*; D007928:Lethal Dose 50; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000633:toxicity; D051379:Mice; D011084:Polycyclic Aromatic Hydrocarbons / Q000008:administration & dosage / Q000633:toxicity*; D012756:Sheep; D013154:Spleen / Q000166:cytology / Q000187:drug effects*; D013329:Structure-Activity Relationship; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology
D002273:Carcinogens; D004731:Endotoxins; D006241:Haptens; D000922:Immunotoxins; D008070:Lipopolysaccharides; D011084:Polycyclic Aromatic Hydrocarbons; C048761:trinitrophenyl-lipopolysaccharide