Effect of chemotherapeutic agents on natural cell-mediated cytotoxicity in mice

Spleen natural killer (NK) activity was investigated in cells from C57BL/6J mice treated with various chemotherapeutic agents; 51Cr-labeled YAC-1 lymphoma cells were used as targets. Treatment with azathioprine (a single injection of 100-400 mg/kg ip or 5 daily doses of 80 mg/kg lp) and cyclophosphamide (a single injection of 50--200 mg/kg ip or 5 daily doses of 25 mg/kg ip) resulted in a marked dose-dependent inhibition of NK activity 2 days later. NK cells recovered rapidly from drug-induced suppression; by 7 days after drug treatment, no difference from control values was observed. Dimethyltriazenoimidazole carboxamide (20--200 mg/kg ip) and adriamycin (10--15 mg/kg iv) did not impair natural cytotoxicity per unit number of lymphoid cells, daunomycin (10 mg/kg iv) caused borderline impairment of NK acitivity, and N-trifluoroacetyl-adriamycin-14-valerate (80 mg/kg iv) markedly suppressed natural cytotoxicity. These results are discussed in light of the known effects of these agents on T-cells, B-cells, and K-cells and on hematopoietic histocompatibility-type reactions.