Variation in the Response of T Cells to Concanavalin a After In Vitro Exposure to Benzo[A]Pyrene and 2-Aminof'luorene

Abstract

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 ß-naphthoflavone (ßNF). We incubated ßnF 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 ßNF indicate that this P-450 inducer enhances the anti-proliferative effect of BP, while it abolishes this effect of AF.