Variation in the response of T cells to concanavalin A after in vitro exposure to benzo[A]pyrene and 2-aminofluorene.
The ability of the polycyclic aromatic hydrocarbon (PAH), benzo[a]pyrene (BP) and its metabolites to be immunosuppressive has been well documented by many investigators. The arylamine, 2-aminofluorene (AF) and its metabolic intermediates have not been as widely studied in this regard. Here, we investigate the effect of BP, 3-hydroxy-BP (3-OH-BP), AF, N-hydroxy-AF (N-OH-AF) and acetyl-AF (AAF) on T-cell proliferation using the T-cell mitogen, Concanavalin A (ConA). These compounds as well as BP-7, 8-diol-9, 10-epoxide (BPDE) were also used to determine their effect on T-cell-mitogen binding. Both AF and BP are substrates for the P-450 and flavin-containing monooxygenase enzyme system, which can be induced with beta-naphthoflavone (beta NF). We incubated beta nF with BP and AF to determine the effect of a P-450 inducer on BP and AF mediated-ConA suppression. Here we demonstrate that BP, 3-OH-BP, AF, and AAF are able to suppress the proliferative response to ConA, while N-OH-AF cannot. Further, we show that BP, 3-OH-BP, BPDE, AF and N-OH-AF do not alter the ability of ConA to bind the mitogen receptor of splenic T-cells, indicating an intracellular mechanism for suppression. Studies with beta NF indicate that this P-450 inducer enhances the anti-proliferative effect of BP, while it abolishes this effect of AF.
Lee
M
M
Department of Microbiology/Immunology, Morehouse School of Medicine, Atlanta, GA 30310, USA.
Kirlin
W
W
Sturrup
M
M
Rodriguez
J
J
Urso
P
P
D000818:Animals; D001564:Benzo(a)pyrene / Q000633:toxicity*; D002273:Carcinogens / Q000633:toxicity*; D003208:Concanavalin A / Q000494:pharmacology*; D005260:Female; D005449:Fluorenes / Q000633:toxicity*; D008213:Lymphocyte Activation / Q000187:drug effects*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008934:Mitogens / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000187:drug effects*
D002273:Carcinogens; D005449:Fluorenes; D008934:Mitogens; D003208:Concanavalin A; D001564:Benzo(a)pyrene; C012177:2-aminofluorene