Cardiac ultrastructural changes induced by daunorubicin therapy

Abstract

To elucidate the mechanisms of the cardiotoxicity induced by daunorubicin (DNR), histologic and ultrastructural studies were made of the hearts of six patients with acute leukemias. Three of these patients had received relatively high total doses (455, 460, and 500 mg/m2) of DNR; one patient had received a relatively low total dose (120 mg/m2) of DNR; two patients who had not been treated with this drug served as controls. Histologic changes observed only in the hearts of the three patients who had received relatively high doses of DNR consisted of scattered foci of damaged, degenerating, and atrophic muscle cells. These changes were more widespread in the patient who had received the highest dose of DNR and developed clinical signs of cardiotoxicity. Alterations of chromatin were observed in 10% of nuclei of cardiac muscle cells in the three patients treated with relatively high doses of DNR. These changes consisted of transformation of variable amounts of chromatin into thick fibers, 160‐200 Å in diameter, intermediate‐sized fibers, 70‐100 Å in diameter, and thin filaments, 30‐40 Å in diameter. These alterations were interpreted as representing various stages of uncoiling and unraveling of chromatin and were considered to be related to the phenomenon of intercalation of DNR into DNA. DNR cardiotoxicity may be related to the inability of non‐dividing cardiac muscle cells to repair DNR‐induced alterations in DNA. Copyright © 1973 American Cancer Society