Susceptibility of murine lymphoma cells treated with 5-(3,3-dimethyl-1-triazenyl)-1H-imidazole-4-carboxamide to NK-mediated cytotoxicity in vitro.
Novel drug-mediated tumor antigens (DMTA) have been detected in chemically induced L5178Y lymphoma of DBA/2 origin, following treatment of tumor-bearing hosts with 5-(3,3-dimethyl-1-triazenyl)-1H-imidazole-4-carboxamide (DTIC). Studies were conducted on the susceptibility of the DTIC-treated subline, maintained in tissue culture, to NK-mediated cytolysis in vitro. The results of the experiments showed that DTIC-treated lymphoma cells are less susceptible to NK cell lysis than the parental line (i.e. L5178Y); the DTIC-treated lymphoma, maintained in vivo as ascitic form, behaved as the corresponding in vitro line, thus suggesting that NK-resistant phenotype was not dependent upon propagation conditions. The intrinsic susceptibility to cell-mediated lysis of the DTIC-treated tumor was unchanged, as demonstrated by lysis produced by alloimmune cytotoxic cells or by natural cytotoxic mesenteric lymph node effectors. "Cold" competition experiments and target binding assay performed with L5178Y/tc and its DTIC-treated subline showed that DTIC-altered cells are less efficient than the parental line as "cold" competitor cells for NK-mediated lysis and bind less efficiently than L5178Y tumor to NK lymphocytes. These data suggested that the NK resistance of the DTIC-treated lymphoma may result from a failure to bind to effector cells, as a consequence of a profound rearrangement of the cell surface produced by DTIC treatment of cancer cells.
D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology*; D003602:Cytotoxicity, Immunologic; D003606:Dacarbazine / Q000276:immunology / Q000627:therapeutic use*; D007113:Immunity, Innate; D007694:Killer Cells, Natural / Q000276:immunology*; D008223:Lymphoma / Q000188:drug therapy / Q000276:immunology*; D051379:Mice
D000951:Antigens, Neoplasm; D003606:Dacarbazine