Effect of dimethylmyleran on cell-mediated immunity to a tumor allograft.
C57BL/6 mice (H-2b) were inoculated on day 0 with killed Moloney lymphoma cells (LSTRA) of BALB/c origin (H-2d), and their spleen cells were tested for reactivity against LSTRA by the 51Cr-release cytotoxicity assay. Cytotoxic reactivity of cells from ice not treated with drug was maximal by day 6 and disappeared by day 10. Cells from mice given dimethylmyleran (DDM) (12 or 16 mg/kg) on day -1 showed higher levels of cytotoxicity, whereas DMM administered on day +1 had little effect. The effect of DMM on the secondary response was tested and compared with that of cyclophosphamide (CY), 180 mg/kg. Cytotoxicity of cells from mice immunized on days 0 and 10 was maximal on day 15 and then declined. CY administered on day 11 prevented the development of any cytotoxicity and, when given on day 14 in the presence of a detectably strong secondary cytotoxic response, abolished the established response. In contrast, DMM given on day 11 delayed the onset and moderately decreased the peaks of secondary reactivity but had no effect when administered on day 14. These results showed that DMM enhanced a primary response, interfered somewhat with the development of a secondary response, and had no effect on an established secondary cell-mediated response to a tumor allograft. DMM thus was one of the rare agents with antitumor activity and little immunosuppressive action.
D000818:Animals; D002066:Busulfan / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000633:toxicity; D003520:Cyclophosphamide / Q000494:pharmacology; D003601:Cytotoxicity Tests, Immunologic; D007111:Immunity, Cellular / Q000187:drug effects*; D007117:Immunization, Secondary; D008223:Lymphoma / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009374:Neoplasms, Experimental / Q000276:immunology; D013997:Time Factors
D003520:Cyclophosphamide; D002066:Busulfan