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RESEARCH PRODUCT

Influence of Mitoxantrone on the Syntheses of Dna and Proteins of Mouse Tissues

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In view of the structural similarity of mitoxantrone to anthracyclines and its ability to intercalate into DNA, we studied its influence on the synthetic processes of DNA and proteins in CD-1 mice tissues. By studying at the DNA level the impairment of 2H-thymidine incorporation and its return to normal, it was found that bone marrow and spleen showed similar behavior, i.e., a rapid return to normal, which occurred before bone marrow cell number and spleen weight returned to basal values. At the cardiac level, the incorporation values of precursors into DNA, reduced by treatment with mitoxantrone, came back very slowly to the control ones. Hepatic DNA showed a lower sensitivity to mitoxantrone. Analysis of 3H-leucine incorporation into three protein fractions of the heart showed that the contractile proteins were the most responsive fractions to mitoxantrone treatment. Experiments on CD-1 mice treated repeatedly with mitoxantrone revealed that the antitumor drug, at the cumulative dose of 8 mg/kg i.v., induced alterations in myocardiac morphology similar qualitatively to those induced by doxorubicin, although smaller quantitatively.