The influence of multiple treatment with doxorubicin or 4'-deoxy-doxorubicin on the DNA synthesis and morphology of mouse heart.

To correlate animal experiments with clinical experience, CD-1 mice were treated weekly for eight weeks with 4 mg/kg doxorubicin or 2.7 mg/kg 4'-deoxy-doxorubicin i.v. Periodically the incorporation of 3H-thymidine (3H-dThd) into DNA was measured in the heart, liver, spleen and bone marrow, 24 or 72 hours after the last treatment. The morphology of the hearts was examined by light microscopy. In animals sacrificed 24 hours after the last treatment, the incorporation of 3H-dThd was reduced considerably and to a similar extent by both molecules in the first weeks, while at the 8th week the values for the heart were higher than in the controls. In the other organs, inhibition percentages of incorporation of 3H-dThd into DNA persisted for both molecules, with higher values in the spleen. In animals killed 72 hours after the last treatment, no change in incorporation capacity was found. These results point to the role of cardiac DNA repair in understanding the pharmacodynamics of these two molecules. The data are discussed in relation to morphology.