A stereological analysis of the effect of adriamycin on the ultrastructure of rat myocardial cells in culture

Abstract

Adriamycin is an effective anti-cancer agent which produces a dose-dependent, irreversible cardiomyopathy of unknown etiology in a significant number of cancer patients. The effect of adriamycin on the ultrastructure of cultured mammalian myocardial cells was examined with light and electron microscope stereological analysis. Cell surface/cell volume, nuclear volume/cellular volume, and nuclear volume/sarcoplasmic volume ratios did not change after adriamycin treatment, showing that the cell volume and sarcoplasm volume were not altered. The nuclear surface area relative to both the nuclear volume and cellular volume was greater in adriamycin-treated cells, implying increased nuclear pleomorphism. The percent of myocardial sarcoplasm occupied by the mitochondria increased very significantly subsequent to adriamycin treatment. That the mitochondria increased in size was indicated by the unchanged mitochondrial surface/cell volume ratio and the decrease in the mitochondrial surface/volume ratio. A significant decrease in glycogen content after exposure to adriamycin as revealed by electron microscope stereological analysis was also observed with the light microscope. Subsequent to adriamycin treatment a small fraction of the cells died and detached from the plate.