Suppression of T lymphocyte proliferation to antigenic and mitogenic stimuli by Benzo(alpha)pyrene and 2-aminofluorene metabolites.
Here, we attempt to reveal how 2-aminofluorene (AF), benzo(alpha)pyrene (BP) and their major metabolites affect T-cell responses to antigenic and mitogenic stimuli. P-450-related metabolism of these parent compounds to metabolites seems to precede the observed immunosuppression; therefore, we investigated the influence of alpha-naphthoflavone (P-450 inhibitor) and beta-naphthoflavone (P-450 inducer) on BP and AF immunosuppression. We used proliferative responses to concanavalin A and the allogeneic mixed lymphocyte response as correlates of immunosuppression. We also attempted to correlate DNA-adduction to the extent of observed immunosuppression for AF and BP metabolites. These data show that the pathway to the strongest immunosuppressive agents for polycyclic aromatic hydrocarbons and arylamines are divergent and related to metabolism by P450 enzymes.
Lee
Mark E
ME
Spelman College, Atlanta, Georgia, USA. marklee@spelman.edu
Urso
Paul
P
D000105:Acetyl Coenzyme A / Q000378:metabolism; D000818:Animals; D000941:Antigens / Q000494:pharmacology*; D001564:Benzo(a)pyrene / Q000494:pharmacology*; D001571:Benzoflavones / Q000494:pharmacology; D002273:Carcinogens / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D003208:Concanavalin A / Q000494:pharmacology; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis; D018736:DNA Adducts / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005449:Fluorenes / Q000494:pharmacology*; D007166:Immunosuppressive Agents; D007376:Interleukin-2 / Q000096:biosynthesis; D007959:Lymphocyte Culture Test, Mixed; D051379:Mice; D008809:Mice, Inbred C3H; D008934:Mitogens / Q000494:pharmacology*; D013154:Spleen / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D013601:T-Lymphocytes / Q000187:drug effects*; D019324:beta-Naphthoflavone / Q000494:pharmacology
D000941:Antigens; D001571:Benzoflavones; D002273:Carcinogens; D065607:Cytochrome P-450 Enzyme Inhibitors; D018736:DNA Adducts; D004791:Enzyme Inhibitors; D005449:Fluorenes; D007166:Immunosuppressive Agents; D007376:Interleukin-2; D008934:Mitogens; D003208:Concanavalin A; D001564:Benzo(a)pyrene; C012177:2-aminofluorene; C011512:alpha-naphthoflavone; D019324:beta-Naphthoflavone; D000105:Acetyl Coenzyme A; D003577:Cytochrome P-450 Enzyme System