Alterations in cell-mediated immune functions induced in mouse splenic lymphocytes by polycyclic aromatic hydrocarbons.

The effects of varying doses of three polycyclic aromatic hydrocarbons, 3-methylcholanthrene (MCA), benzo(a)pyrene (BaP), and benzo(e)pyrene (BeP), on cell-mediated immune functions of in vivo mitogen-activated splenic lymphocytes were measured. Inbred mice (C57, C3H, and DBA) were given injections i.p. with phytohemagglutinin to activate splenic lymphocytes and were subsequently treated, via the same route, with polycyclic aromatic hydrocarbon compounds. Isolated and T-cell-enriched mononuclear cell populations were assayed for aryl hydrocarbon hydroxylase activity, blastogenesis, antigen-specific cell-mediated cytotoxicity, and the percentage of macrophages. Under optimal conditions of phytohemagglutinin injection (1000 micrograms/20-g mouse) for 96 hr and MCA treatment (50 mg/kg of body weight) for 24 hr prior to sacrifice, aryl hydrocarbon hydroxylase was induced 5-fold. Tumorigenic doses of MCA (10 to 50 mg/kg of body weight) suppressed blastogenesis 40 to 60% in C57 and C3H lymphocytes but had no effect on DBA splenic lymphocytes. BaP and BeP had little or no effect on blastogenesis. MCA and BaP were clearly separated from BeP in the suppression of cell-mediated cytotoxicity. MCA and BaP suppressed cell-mediated cytotoxicity 40 to 80% in T-cells from all three strains, while BeP had no effect. MCA reduced the percentage of macrophages in a dose-dependent fashion compared to a stimulatory action by BaP and BeP. These results suggest that mitogen-activated and aryl hydrocarbon hydroxylase-induced splenic lymphocytes metabolize MCA and BaP to immunocytotoxic metabolites. A suppression of monocyte-macrophage function would account for the inhibition of blastogenesis. These early alterations in cell-mediated immune functions produced by tumorigenic doses of MCA and BaP may result in defective immunosurveillance mechanisms and enhance the development of polycyclic aromatic hydrocarbon-induced tumors in responsive mice.