Effects of Adriamycin on rat heart cells in culture: Increased accumulation and nucleoli fragmentation in cardiac muscle v. non-muscle cells

Primary cultures from neonatal rat hearts consist of morphologically distinguishable cardiac muscle and non-muscle cells. The relative fluorescence intensity and nucleolar effects of Adriamycin (ADR) have been studied in these different cell types by fluorescence and phase-contrast microscopy. In cultures exposed to ADR (10 μg/ml) for 30 min, or continuously for 24 h, the intensity of drug-specific fluorescence was significantly greater in the nuclei of muscle, as compared to non-muscle cells. Consistent with these differences in cytofluorescence, nucleolar fragmentation was observed in muscle cells 24 h after a 30-min exposure to ADR, whereas non-muscle cell nucleoli remained intact. With N-trifluoroacetyladriamycin-14-valerate (AD 32), a potent ADR analog, fluorescence was observed in the cytoplasm of both muscle and non-muscle cells; no difference in the intensity of fluorescence between these two cell types was detected. Based on these observations, we believe that drug-induced nucleolar fragmentation in cardiac muscle cells results from higher ADR levels than those achieved in non-muscle cells, and that these differences may have relevance with respect to anthracycline-induced cardiotoxicity in vivo.