Effect of Chemotherapeutic Agents on Natural Cell-Mediated Cytotoxicity in Mice2

Abstract

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 dally doses of 80 mg/kg ip) and cyclophosphamide (a single Injection of 50–200 mg/kg ip or 5 dally 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. Dimethyitriazenoimidazole carboxamlde (50–200 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 activity, 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 reactlons.