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.
D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects*; D001379:Azathioprine / Q000009:adverse effects; D003520:Cyclophosphamide / Q000009:adverse effects; D003602:Cytotoxicity, Immunologic / Q000187:drug effects*; D003606:Dacarbazine / Q000009:adverse effects; D004317:Doxorubicin / Q000009:adverse effects; D007113:Immunity, Innate / Q000187:drug effects*; D007165:Immunosuppression Therapy; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D013154:Spleen / Q000276:immunology
D000970:Antineoplastic Agents; D003606:Dacarbazine; D004317:Doxorubicin; D003520:Cyclophosphamide; D001379:Azathioprine