Alterations in Cell-mediated Immune Functions Induced in Mouse Splenic Lymphocytes by Polycyclic Aromatic Hydrocarbons1

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 func tions of in vivo mitogen-activated splenic lymphocytes were measured. Inbred mice (C57, C3H, and DBA) were given injec tions i.p. with phytohemagglutinin to activate splenic lympho cytes and were subsequently treated, via the same route, with polycyclic aromatic hydrocarbon compounds. Isolated and Tcell-enriched mononuclear cell populations were assayed for aryl hydrocarbon hydroxylase activity, blastogenesis, antigen-spe cific cell-mediated cytotoxicity, and the percentage of macro phages. Under optimal conditions of phytohemagglutinin injection (1000 Ã-Ã-g/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 com pared 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 blastogen esis. 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 de velopment of polycyclic aromatic hydrocarbon-induced tumors in responsive mice.