Drug-binding macromolecular lipids from L1210 leukemia tumors.

The isolation and purification of at least two distinct macromolecular lipids from murine L1210 tumors either sensitive or resistant to the terephthalanilide NSC 38280 are described. The lipids are extracted from the tumors with chlorofornrmethanol and purified utilizing a series of gel permeation and affinity chromatography columns with chlorofornrmethanol elution. Preliminary characterization of the macromolecular lipids indi cates that they have low molecular weights (>10,000 but <25,000) and are comprised of lipid, carbohydrate, and polyamino components. Significant differences were found be tween the component composition, molecular size, and column elution properties of the two lipids. One of the macromolecular lipids is extractable from both sensitive and resistant tumors and binds terephthalanilides, Cain quinoliniums, a carbanilide, bis(substituted aminoalkylamino)anthraquinones, and Adriamycin. The other macromolecular lipid appears to occur only in resistant tumors and does not bind the terephthalanilides, Cain quinoliniums, or the carbanilide. Further, the binding studies may predict a correlation between drug binding to the lipids in vitro and drug activity against L1210 leukemia and other tumors in vivo. The polyamine, spermine, also binds to the macromolecular lipids and can displace drugs bound to the lipids. Such spermine displacement of drug binding is either competitive or noncompetitive in nature depending on the cell line origin of the lipid. The isolated macromolecular lipids may represent components of binding sites for cancer-chemotherapeutic drugs in vivo.