SENSITIVITY OF DRUG-RESISTANT B-CELL LINES FROM AIDS-RELATED NON-HODGKINS-LYMPHOMA TO NEWLY SYNTHESIZED PODOPHYLLOTOXIN DERIVATIVES AND AZA-ALKYLLYSOPHOSPHOLIPIDS - ENHANCED SENSITIZATION BY PRETREATMENT WITH INTERFERON-GAMMA

: Non-Hodgkin's lymphoma B cells (NHL-B) often become refractory to conventional chemotherapeutic drugs. The present study investigated the sensitivity of three AIDS-derived NHL-B cell lines to newly synthesized azaalkyllysophospholipids (AALP) and podophyllotoxin derivatives. All three cell lines were sensitive to 5 AALP derivatives and toxicity was detectable at 24 h of culture and was increased at 48 and 72 h of incubation. Toxicity was concentration-dependent and die extent of cytotoxicity varied slightly from one cell line to another. These cell lines were less sensitive to the podophyllotoxin derivatives VP-16, BDPTN and BEPT than to die AALP. This was shown by the extent of cytotoxicity calculated on a molar basis and by the delayed kinetics of lysis. Pretreatment of the tumor cells with IFN-gamma stimulated cell proliferation. IFN-gamma treated tumor cells were also tested for their sensitivity to the various cytotoxic agents. In all cases, the sensitivity of the IFN-gamma pretreated cell lines to the podophyllotoxin derivatives and AALP was significantly enhanced. These findings demonstrate that drug resistant NHL-B cells are sensitive to a new family of AALP and podophyllotoxin derivatives. Further, the sensitivity of the tumor cells was enhanced by treatment with IFN-gamma. The potential clinical use of these new cytotoxic agents to overcome resistance of AIDS-related cell lymphomas is discussed.