Suppression of mitogen-induced blastogenesis of feline lymphocytes by in vitro incubation with carcinogenic nitrosamides

Abstract

Effects of brief in vitro incubation with nitrosamides on the lymphocyte blast transformation (LBT) response of feline peripheral blood mononuclear cells (PMC) to concanavalin A (con A) was studied. Incubation for 1/2 hr with 10--100 microgram/ml methylnitrosourea (MNU) or 0.1-2.01 microgram/ml methyl-N-nitrosoquanidine (MNNG) caused marked suppression of the normal LBT response. This effect was not due to cytotoxicity, since viability experiments showed no significant decrease in viability for any concentration of either MNU or MNNG. MNU caused suppression when added to PMC cultures 24 hr, but not 48 hr, after initiation of stimulation with con A. Biologically inactivated MNU also caused suppression of the LBT response, similar in magnitude to active MNU. Finally, serum from cats immunologically suppressed by MNU did not cause suppression of the LBT response of normal feline PMC. It was concluded that the immunosuppressive properties of MNU previously noted in vivo are probably due to a direct suppressive effect on lymphocytes and/or macrophages, and that the decreased LBT response to con A of MNU-treated PMC is an accurate reflection of the immunosuppression seen in vivo.