Effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin on macrophage and natural killer cell-mediated cytotoxicity in mice.

C57Bl/6 J mice (6-8 weeks old) were given single i. p. doses (1, 2, 6 and 30 micrograms/kg) of 2,3,7,8-tetrachloro-dibenzo-p-dioxin (TCDD) and macrophage-mediated and natural killer (NK) cell-mediated cytotoxicity was evaluated at different times after treatment. Peritoneal macrophage cytolytic activity was measured as 3H-thymidine release from prelabelled mKSATU5 target cells in a 48 hours assay; macrophage-mediated cytostasis was assessed in terms of inhibitions of 3H-thymidine uptake by SL2 lymphoma cells. Spleen NK activity was measured using 51Cr-labelled YAC-1 lymphoma cells as targets. TCDD did not modify spontaneous macrophage-mediated and NK cell-mediated cytotoxicity per unit number of effector cells nor did it affect the macrophages' capacity to express increased cytolytic and cytostatic activity in the presence of endotoxin. Lower numbers of peritoneal macrophages and splenocytes were recovered from TCDD treated mice. Thus the total numbers of lytic units recovered from animals exposed to TCDD were lower than controls. Impairment of these cellular effector mechanisms, due to cell loss rather than inhibition of function, might play a role in the lowered resistance to bacterial infection of mice given TCDD and in the carcinogenic and cocarcinogenic activity of this chemical.