PARTITIONING AND STRUCTURAL EFFECTS OF THE ANTITUMOR DRUG DAUNOMYCIN ON MODEL MEMBRANES

The effects of the antitumor drug daunomycin on the phase transition a nd dynamic properties of phosphatidylcholine membranes were investigat ed using the electron paramagenetic resonance spin labeling method. Mu ltilamellar liposomes made of saturated dimyristoylphosphatidylcholine and unsaturated egg yolk phosphatidylcholine were used. The main phas e transition of saturated bilayer was significantly broadened in the p resence of daunomycin. In the fluid phase of saturated membranes, daun omycin caused a decrease in the rotational motion of the spin probe 16 -doxylstearic acid (16-SASL). This effect was strongly diminished by r aising the temperature. In unsaturated membranes no influence of dauno mycin on the rotational motion of 16-SASL was observed. It is proposed that the neutral form of daunomycin can partition into lipid bilayer where it can diffuse into deeper hydrophobic regions of the membrane a nd decrease the motion of alkyl chains.