In vitro and in vivo study of cross resistance between daunorubicin and daunorubicin-DNA complex in Ehrlich ascites tumor.

The antitumor effect of daunorubicin and of two preparations of daunorubicin-DNA complexes were compared in equitoxic doses against the Ehrlich ascites tumor and in a subline of this tumor resistant to daunorubicin. The therapeutic efficacy of both complexes was significantly better than that of free daunorubicin in the sensitive tumor. The daunorubicin-resistant tumor was found to be cross resistant to both daunorubicin-DNA complexes. In vitro, the steady-state uptake of daunorubicin was considerably lower when the drug was added as a complex compared with addition as free drug. Experiments in which the uptake of daunorubicin and of DNA was determined simultaneously showed no significant uptake of DNA in either cell line. Together, these data indicate that even if daunorubicin is administered as a complex, the membrane transport in Ehrlich ascites tumor cells takes place solely as free drug.