2-AMINO-3-METHYLIMIDAZO[4,5-F]QUINOLINE-MEDIATED IMMUNOSUPPRESSION INVOLVES INHIBITION OF PROTEIN-KINASE-C IN MURINE SPLENOCYTES

The effects of the food-borne mutagenic and carcinogenic heterocyclic amine, 2-amino-3-methylimidazo[4,5-f]quinoline (IQ), on the proliferat ion of murine spleen cells was examined. A significant and dose-relate d suppression of the proliferative response to concanavalin A (Con A) was observed by the treatment of IQ. IQ also decreased markedly the le vel of proliferative response induced by PMA and ionomycin and the IL- 2 secretion by T cells. Treatment of PMA resulted in the recovery of I Q-induced suppression of IL-2 production, but the addition of ionomyci n (Io) had no effect, IQ decreased PKC activity in both the membrane f raction and the cytosol fraction and inhibited the phosphorylation of MARCKS protein. These results suggest that the suppression of spleen c ell proliferation induced by IQ might be associated with the inhibitio n of PKC activity and the subsequent IL-2 secretion of T cells.